GUIDE TO ANTIMICROBIAL THERAPY FOR ADULTS

Transcription

GUIDE TO
ANTIMICROBIAL THERAPY
FOR ADULTS
FLETCHER ALLEN HEALTH CARE
10th Edition
2006-2007
PREPARED BY:
THE INFECTIOUS DISEASE PRACTICE COMMITTEE
Christopher Grace, MD, Co-Chairman (Infectious Disease)
John Ahern, PharmD, BCPS Co-Chairman & Editor (Pharmacotherapy)
Kemper Alston, MD (Infectious Disease)
Elizabeth Bonney (Obstetrics & Gynecology)
David Clauss, MD (Emergency)
Thomas Connolly, DMD (Surgery)
Maj Eisinger, MD (Emergency)
Steve Grant (Internal Medicine)
Beth Kirkpatrick, MD (Infectious Disease)
Karen McBride (Pharmacotherapy)
Christine Northrup, MD (Internal Medicine)
Tom Peterson, MD (Family Practice)
Mary Ramundo, MD (Infectious Disease)
Michael Young, MD (Intensive Care)
Washington Winn, MD (Microbiology)
Approved by :
The Executive Committee
The Pharmacy and Therapeutics Committee
Copyright Fletcher Allen Health Care, Inc. 1996
1
TABLE OF CONTENTS
Introduction ............................................................................................................. 4
Balance the Risk ..................................................................................................... 5-6
Common Sense Guidelines to Infectious Disease Management............................ 7
Description of the Antimicrobial Management Program at FAHC ........................... 8
Antimicrobial Drugs on the FAHC Formulary .......................................................... 9
FAHC Microbiology Susceptibility Chart ................................................................. 10
Aminoglycoside Antibiotics ..................................................................................... 11-15
• General Principles .................................................................................. 11
• Once Daily Dosing .................................................................................. 12-13
• Traditional Dosing................................................................................... 14-15
Vancomycin ............................................................................................................ 16-17
• Criteria for Use........................................................................................ 16
• Dosing and Monitoring............................................................................ 17
Guidelines for Criteria-Based Antibiotics ................................................................ 18-22
•
•
•
•
•
•
Ampicillin / sulbactam ............................................................................. 19
Azithromycin ........................................................................................... 20
Cefotetan ................................................................................................ 20
Ceftriaxone ............................................................................................. 21
Levofloxacin............................................................................................ 22
Norfloxacin.............................................................................................. 22
Guidelines for Selected Controlled Antibiotics ........................................................ 23-27
•
•
•
•
Ceftazidime............................................................................................. 24
Ciprofloxacin ........................................................................................... 25
Piperacillin / tazobactam......................................................................... 26
Meropenem............................................................................................. 27
Guidelines for Specific Infections............................................................................ 28-61
•
•
•
•
•
•
•
•
•
•
•
Community and Nosocomial / Nursing Home Acquired Pneumonia....... 29-32
Intra-abdominal Infections ...................................................................... 33-37
Urinary Tract Infections........................................................................... 38-39
Diabetic Foot Infections .......................................................................... 40-41
Fever and Neutropenia ........................................................................... 42-43
Female Upper Genital Tract Infections ................................................... 44-45
Bite Wound Infections............................................................................. 46-47
Infectious Diarrhea & C. difficile.............................................................. 48-52
Principles of Surgical Prophylaxis........................................................... 53-55
Prevention of Bacterial Endocarditis....................................................... 56-58
Therapy for Selected Sexually Transmitted Diseases ............................ 59-60
2
• Post-Exposure Prophylaxis..................................................................... 61
3
Oral Antimicrobial Therapy.......................................................................... 62-69
•
•
•
•
•
•
•
•
•
•
Introduction ............................................................................................. 63
Selected Oral Agents.............................................................................. 64-66
-Amoxicillin/clavulanate .................................................................. 64
-Azithromycin .................................................................................. 64
-Cefpodoxime ................................................................................. 65
-Ciprofloxacin.................................................................................. 65
-Levofloxacin................................................................................... 66
-TMP/SMX ...................................................................................... 66
IV to PO Switch Table............................................................................. 67
Costs to Patients..................................................................................... 68-69
Antibiotic Prescribing .............................................................................................. 70-75
• Renal Dosing Table ................................................................................ 71
• Important Antimicrobial Drug Interactions............................................... 72-73
• Antimicrobials in pregnancy.................................................................... 74-75
DISCLAIMER
This handbook is provided solely as a general guide. The information contained in this handbook
is presented in summary form and does not constitute medical advice. As medical advice must be
tailored to the specific circumstances of each individual patient, and because medical knowledge
changes rapidly, nothing provided in this handbook should be used as a substitute for medical advice
or the judgement of the responsible clinician. Readers are encouraged to consult numerous sources
in determining the appropriate patient treatment.
The authors have used sources believed to be reliable in compiling the information contained in this
handbook. However, neither the authors, Fletcher Allen Health Care, Inc. nor the University of Vermont
make any claims, promises or guarantees about the accuracy, completeness or adequacy of this
information. They are also not responsible for any errors or omissions or for the results obtained from
the use of this information.
4
INTRODUCTION
The purpose of this handbook is to provide guidance to the clinician in the management of
infectious diseases in adult patients. Since all patient care needs to be individualized, this
handbook is not all inclusive nor is the content meant to represent a rigid approach to care. It
has been written by the Infectious Disease Practice Committee, a subcommittee of the
Pharmacy and Therapeutics Committee. It has been tailored specifically for Fletcher Allen
Health Care. This is the fourth edition of the booklet and future editions will be expanded and
updated. Please feel free to contact any member of the committee
with feedback and suggestions for future editions.
Through the use of this guide, it is hoped that antimicrobial agents will be used judiciously.
The modern era of antibiotic therapy has seen great advances in the management of
infectious diseases. However, these advances have brought two major detrimental trends:
1. INCREASING RESISTANCE TO ANTIBIOTICS: Since the development of resistance
by Staphylococci to penicillin early after its introduction in the 1940’s, the overuse of
antimicrobial agents has been associated with the development of resistant pathogens.
The emergence of multiply resistant gram-negative and gram-positive bacteria has
become a medical emergency that threatens our ability to treat and cure our patients.
The overuse of any antibiotic will lead to resistance to that agent. This is especially
true for the newer broad spectrum agents such as the second and third generation
cephalosporins (cefotetan, ceftriaxone, ceftazidime) carbapenems (imipenem and
meropenem), beta-lactamase inhibitor combinations (amoxicillin-clavulanate, ampicillinsulbactam, piperacillin-tazobactam), fluoroquinolones (ciprofloxacin, norfloxacin,
levofloxacin and trovafloxacin), and glycopeptide (vancomycin) antibiotics. Multiply
resistant E.coli, Klebsiella, Pseudomonas, Acinetobacter, Staphylococci and
Enterococci (to name but a few) are increasing at FAHC due in large part to the
overusage of antibiotics.
The use of any antibiotic must be looked upon as a double edged sword. In
addition to killing the bacteria infecting your patient the drug you prescribe will select for
resistant bacteria. These resistant bacteria may not only infect your patient but may also
be spread to other patients in the hospital, clinics, and community (esp. nursing homes).
2. INCREASING COSTS: There will continue to be intense pressure on us to control the
costs of health care while maintaining the quality of care for our patients. In this age of
managed care and capitated costs we must be cognizant of the expense of the
antibiotics we prescribe. There are many therapeutic options available to us when
treating our patients (that is, there are many ways to skin a bacterium). Efforts to use
less costly though equally effective agents must be made. The newer more expensive
heavily marketed agents are not necessarily better.
5
BALANCE THE RISK
We are please to provide you the latest edition of the FAHC “Green Book”. This pocket
book is meant to help you prescribe antibiotics judiciously and safely. With delivery of
this book comes a concern and a plea.
There has been an alarming increase in infections with methicillin resistant
Staphylococcus aureus, (MRSA) and Clostridium difficile colitis. Both of these
infections are related to the overuse of antibiotics. The relationship between
increasing drug use and increasing infection is clear. These nosocomial infections
result in significant patient morbidity, mortality, length of stay and costs. Our
current bed availability problems are exacerbated by these infections.
Antibiotic use has been shown to increase nosocomial colonization with MRSA (relative
risk as high as 11.3) and C. difficile (relative risk as high as 28.6) [Safdar N and Maki DG,
Ann Int Med 2002;136:834-844]
It is important to BALANCE THE RISK (toxicities, superinfections, and costs) of using
antibiotics against the benefit you hope to achieve. Traditionally we have leaned in the
direction of more antibiotics, not less, in treating our patients. Often though, the antibiotics
we depend on to cure infections are causing infections themselves. With each antibiotic
prescription you write, a balance must be struck between the desired benefits of the
antibiotic and the risks those antibiotics may cause.
6
In order to reduce the incidence of these infections we need to decrease our
antibiotic use, especially broad-spectrum agents. The following questions
should be reviewed before prescribing antibiotics:
Does the patient really need the antibiotic?
Does the risk of using the antibiotic out-weight the risk to your patient of
contracting MRSA or C.difficile colitis?
Can you narrow the spectrum of the antibiotic from the initial empiricism or
once culture data is available?
Can you switch to oral agents once your patient has stabilized?
We encourage the use of Infectious Diseases consultation to assist you with
making these important decisions.
Remember to
Balance the Risk
7
COMMON SENSE GUIDELINES TO
INFECTIOUS DISEASE MANAGEMENT
1)
Before judging the importance of a culture, consider the clinical diagnosis. Not
all positivecultures need treatment and a negative culture does not exclude
infection.
2)
A good history and physical is far more important than “pan-culturing”.
3)
Not all fevers are due to infection. Not all patients with infection have fevers.
4)
Always get appropriate cultures prior to starting therapy. Culturing the patient
while on antibiotics has a low yield.
5)
Review the gram stain of a specimen such as sputum when attempting to
determine the need to treat a positive culture. Many positive cultures represent
contamination or colonization and may not need to be treated.
6)
Use the most narrow spectrum agent available in treating your patient’s
infection.
7)
Whenever you select an antibiotic know how much it will cost. Attempt to select
the less expensive though equally effective antibiotic.
8)
When your patient stabilizes, consider switching to oral therapy if appropriate.
9)
If the patient is failing empirical antibiotic therapy, a re-evaluation of the cause
of the failure is more important than broadening or changing the empirical
antibiotic regimen.
10) The antibiotic you give to your patient goes not only to the site of infection but
to all the tissues of your patient. It will alter the normal (protective) skin,
bowel, and oral flora of your patient. Resistant pathogens can replace the
normal flora and may then cause infections.
8
ANTIMICROBIAL MANAGEMENT PROGRAM
1. Formulary System:
The formulary is the group of antimicrobials available for use by FAHC staff. The formulary
antimicrobials are divided into three main classes which determines how they may be
prescribed:
a. Open
Antibiotics that are intended for routine use and have no restrictions.
b. Criteria based
Antibiotics that may be utilized only for the criteria as outlined on pages 19-22.
Use of these agents will be monitored. Utilization of these antibiotics for
situations not listed in the criteria requires approval by Infectious Disease.
c. Controlled
Antibiotics that require approval by Infectious Disease before they can be
prescribed. These agents will not be released by the Pharmacy until they are
notified by Infectious Disease to do so. Exceptions to this rule are noted on the
formulary list on page 9. Please note that controlled antibiotics can be
prescribed between the hours of 10 PM and 8 AM without infectious disease
approval. However, infectious disease must be called in the morning for
approval to continue the antibiotic.
2. Monitoring and Evaluation:
Pharmacy and Infectious Disease will review use of all criteria-based and
controlled antibiotics within 48-72 hours after the initial dose. Housestaff will be
contacted with suggestions for change by the infectious disease pharmacist.
The results of current antibiotic reviews suggest the need for improvement in
the following two areas:
a. Narrowing the spectrum of antibiotic therapy once culture and sensitivity
results are available.
b. Utilizing the oral route of administration for antibiotics that have reliable oral
absorption. See page 63.
3. Emergency Department , intensive care units, and cystic fibrosis patients
Controlled antibiotics may be prescribed without infectious disease approval for
use in the Emergency Department, for use in the Medical and Surgical Intensive
Care Units, and for the treatment of cystic fibrosis patients.
9
ANTIMICROBIAL AGENTS ON THE FAHC FORMULARY FOR ADULTS
OPEN
CRITERIA-BASED
CONTROLLED
Parenteral
Ampicllin
Cefazolin
Cefuroxime
Clindamycin
Co-trimoxazole
Doxycycline
Erythromycin
Gentamicin
Metronidazole
Nafcillin
Penicillin G
Piperacillin
Parenteral
Ampicillin / sulbactam
Azithromycin
Cefotetan
Ceftriaxone
Levofloxacin
Tobramcyin
Vancomycin
Parenteral
Acyclovir *4
Amikacin
Amphotericin B deoxycholate
Amphotericin B liposome
Aztreonam
Caspofungin
Ceftazidime *1
Cefepime *1
Ciprofloxacin*5
Fluconazole *4
Ganciclovir *3
Itraconazole
Linezolid
Meropenem *1
Pentamidine
Piperacillin / tazobactam
Quinupristin / dalfopristin
Voriconazole
Oral
Acyclovir
Amoxicillin
Amoxicillin / clavulanate
Cephalexin
Cefpodoxime proxetil
Clindamycin
Co-trimoxazole
Dicloxacillin
Doxycycline
Erythromycin
Isoniazid
Ketoconazole
Metronidazole
Neomycin
Nitrofurantoin
Nystatin
Penicillin VK
Rifampin
Oral
Azithromycin
Clarithromycin
Famciclovir
Levofloxacin
Norfloxacin
Vancomycin
Valacyclovir
Oral
Ciprofloxacin *5
Dapsone
Fluconazole *2, *4
Fosfomycin
Ganciclovir *3
Itraconazole
Linezolid
Ofloxacin
Voriconazole
Topical
Mupirocin
* These drugs can be used without ID approval for the specific indications listed below:
1
2
3
4
5
Febrile neutropenic patients (ANC <500)
One dose (150 mg) treatment of vaginal candidiasis
Renal transplant patients with suspected or documented CMV infection
Stem cell patients
For prevention of bacterial infections in cirrhotic patients with GI bleeding
10
ANTIMICROBIAL SUSCEPTIBILITY RESULTS
FLETCHER ALLEN HEALTH CARE
July 1, 2004 through June 30, 2005
Max strains tested
Escherichia
Enterobacter
Klebsiella
Proteus
Proteus
Serratia
Acinetobacter
Citrobacter
Pseudomonas
Staphylococcus
Coag
Coag
pos
neg
Enterococcus***
species
species
species
Mirabilis
species
species
species
Freundii
Aeruginosa
3088
269
721
218
60
97
34
73
1095
1928
516
805
Streptococcus
Pneumoniae
% Susceptibile
Ampicillin
72
5
1
93
8
14
18*
10
2
**
**
95
--
Ampicillin/Sulbactam
70
20
78
100
58*
10
--
--
2
--
--
--
--
Amikacin
99
97
100
--
--
--
--
--
71
--
--
--
--
Aztreonam
99
83
99
99
95
99
13*
76
81
--
--
--
--
Ceftazidime
99
85
99
100
86
99
73*
73
85
--
--
--
--
Ceftriaxone
99
85
100
100
100
94
38*
74
31
--
--
--
--
Clindamycin
--
--
--
--
--
--
--
--
--
#
#
--
--
Ciprofloxacin
95
97
98
91
92
94
97*
92
71
66
54
70
--
Cefotetan
86
79
97*
--
--
--
--
--
7
--
--
--
--
Cefazolin
97
9
97
98
14
1
0*
6
1
65
35
--
--
Cefepime
99
99
100
97
100
100
--
100
83
--
--
--
Cephalothin*****
86
--
--
--
--
--
--
--
--
--
--
--
--
Co-trimoxazole
86
94
95
87
88
94
88*
88
15
--
--
--
--
Erythromycin
--
--
--
--
--
--
--
--
--
49
40
--
--
Gentamicin
97
100
100
96
98
100
79*
96
75
--
--
--
--
Imipenem
99
99
100
99
100
99
100*
100
84
--
--
--
--
Meropenem
99
100
100
--
--
--
--
--
89
--
--
--
--
Oxacillin/Nafcillin
--
--
--
--
--
--
--
--
--
65
--
--
--
Oxacillin/Nafcillin
--
--
--
--
--
--
--
--
--
--
35
--
--
Piperacillin
57
82
100
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
91
--
--
--
--
84
98
99
100
94
94*
83
--
--
--
--
--
Piperacillin
Piperacillin/Tazobact
99
Piperacillin/Tazobact
--
--
--
--
--
--
--
--
93
--
--
--
--
Tobramycin
98
100
99
96
100
91
82*
99
88
--
--
--
--
Vancomycin
--
--
--
--
--
--
--
--
--
100
100
99
--
Penicillin
69 (15% Int)
Ceftriaxone (CSF)
67
Ceftriaxone (serum)
*===<50 strains tested
**== At FAHC >90% of Staphylococcus sp. are resistant to penicillin and ampicillin
***== For serious enterococcal infections combination therapy with a beta lactam and an aminoglycoside antibiotic should be used.
****== 66 pneumococcal strains tested against ceftriaxone; only strains NOT susceptible to penicillin in a screening procedure tested against ceftriaxone
*****== Cephalothin should be used as the class drug for determining susceptibility to oral first generation cephalos1porins
# == Staphylococci and streptococci not tested against erythromycin resistant strains routinely
91
11
AMINOGLYCOSIDE ANTIBIOTICS
1. General principles:
a. All aminoglycosides are equally effective against susceptible gram-negative bacteria and
cause a similar incidence of toxicity. Gentamicin is the least expensive and is therefore the
aminoglycoside of choice for most gram-negative infections.
b. For maximum bactericidal effect, doses to achieve high peak serum levels but very low trough
levels are employed. This is commonly referred to as once daily aminoglycoside therapy.
c. With traditional or high dose aminoglycoside therapy, the incidence of renal or ototoxicity is
very low (<5%). In patients who are at high risk for toxicity (see section 4 below), alternative
antimicrobials should be considered.
d. For serious gram-negative infections the use of aminoglycosides with beta-lactam antibiotics
for synergistic effect is encouraged and often necessary to ensure clinical cure.
e. Aminoglycoside dosing is based on actual body weight unless the patient is obese then a
dosing weight needs to be calculated (see section 3 on page 12).
2. Aminoglycosides on formulary:
a. Gentamicin - aminoglycoside of choice for susceptible organisms
b. Tobramycin - for gentamicin resistant infections only
c. Amikacin - requires ID approval
3. Indications and recommendations for appropriate use:
a. Infections due to susceptible gram-negative bacteria
b. Use with beta-lactam antibiotic for synergistic effect is recommended for the
treatment of the following serious infections:
1. Serious gram-negative infections (Pseudomonas, Enterobacter, Serratia, etc)
2. Serious enterococcal infections
3. Febrile neutropenic patient
4. Patients at increased risk for development of nephrotoxicity and ototoxicity:
a.
b.
c.
d.
e.
f.
g.
Elderly (decreased renal tubule cell regenerative capacity)
Duration of therapy > 1 week (accumulation effect)
Prior aminoglycoside therapy within one month
Concurrent nephrotoxic drugs (amphotericin B, cyclosporine, etc)
Prolonged elevated trough concentrations (accumulation effect)
Episodes of excessive diuresis, hypovolemia, or shock (poor renal perfusion)
Pre-existing renal or liver disease
5. Relative contraindications to use:
a. History of hypersensitivity reactions to aminoglycosides
b. History of hearing loss or vestibular dysfunction, particularly in patients with impaired vision and
peripheral neuropathy
c. Diabetes
d. Pre-existing renal or liver disease
12
ONCE-DAILY AMINOGLYCOSIDE THERAPY
FOR GENTAMICIN AND TOBRAMYCIN
1. Preferred method for most adult patients (see exclusion criteria under #5 below)
2. Initial dose (see section 2 on page 14 for information on how to calculate creatinine
clearance)
Creatinine Clearance
Dose and Interval
>60 ml/minute
7 mg/kg every 24 hours
40 to 60 ml/minute
7 mg/kg every 36 hours
3. Dose based on actual body weight (ABW) unless patient obese (20% over ideal body
weight [IBW]).
IBW (males) = 50kg + 2.3kg/inch over 5 ft
IBW (females) = 45.5kg + 2.3 kg/inch over 5 ft
Obese dosing weight = IBW + 0.4(ABW - IBW)
4. Monitoring and dose adjustment:
a. Pharmacy will order a single random serum level after the first dose between 6 and
14 hours after the start of the infusion.
b. Using nomogram (on following page), serum level will be evaluated by Pharmacy
and, if necessary, dose adjustment recommended.
c. If treatment continues for more than 5 days, a second random level will be ordered
by Pharmacy.
d. For patients receiving prolonged therapy or in the intensive care units, serial serum
levels will be ordered and evaluated by Pharmacy in order to more accurately
individualize the dose.
5. Patients excluded from 7 mg/kg once-daily dosing:
a.
b.
c.
d.
e.
f.
Pediatric patients
Pregnant patients
Patients with estimated CrCl < 40 ml/min
Patients with ascites, endocarditis, or severe burn injury
Cystic fibrosis patients
Patients with dosing intervals > 48 hours per nomogram
13
14
TRADITIONAL AMINOGLYCOSIDE DOSING METHOD
For adult patients excluded from once-daily dosing (see section 5 on page 12)
1. Loading dose:
Gentamicin
2 mg/kg
Tobramycin
2 mg/kg
Amikacin
7.5 mg/kg
The loading dose should be based on actual body weight (ABW).
2. Maintenance dose:
a. Calculate creatinine clearance (standardized to 72 kg):
Males = 140 - age
Scr
Females = 0.85 x Males
For patients with a reported serum creatinine of < 1 mg/dl, consider rounding the serum
creatinine to 1 mg/dl. This issue may be clinically important in patients > 60 years of
age, or in patients with reduced muscle mass resulting from cachexia, malnutrition, or
spinal cord injuries
b. Find the estimated creatinine clearance on the left hand column of the nomogram which
is located on the next page.
c. Move to the right along the nomogram to find the desired dosing interval (q8, q12, q24).
The maintenance dose will be a percentage of the loading dose.
Example:
55 kg 80 year old female with a Scr of 1.3 mg/dl. The loading dose should
be 110 mg. The creatinine clearance is 39 ml/min. The maintenance dose
should be 100 mg q24.
3. Monitoring and dose adjustment:
a. Pharmacy will order peak and trough serum levels within 48 hours of initial dose unless
therapy is less than 3 days.
b. Based on a pharmacokinetic evaluation of serum levels, pharmacy will recommend a
dosing adjustment if necessary.
c. Subsequent peak and trough serum levels will be ordered and evaluated by pharmacy
at 5 to 7 day intervals.
d. It is suggested that a serum creatinine be obtained at least qod while the patient is
receiving aminoglycoside therapy.
15
NOMOGRAM FOR CALCULATING AMINOGLYCOSIDE
MAINTENANCE DOSE USING TRADITIONAL METHOD
PERCENTAGE OF LOADING DOSE REQUIRED
FOR DOSE INTERVAL SELECTED
CRCl (ml/min.) Half life (hours)
8 hours
12 hours
24 hours
> 100
2.5
100%
--90
3.1
84
--80
3.4
80
91%
-70
3.9
88
-60
4.5
84
-50
5.3
79
-40
6.5
92%
30
8.4
86
25
9.9
81
20
11.9
75
17
13.6
70
< 15
15.1
CONSULT WITH PHARMACIST
IF AGE > 60, DO NOT USE 8 HOUR INTERVAL
16
VANCOMYCIN
Vancomycin is a glycopeptide antibiotic with activity against gram-positive pathogens (except
vancomycin resistant enterococcus). The oral formulation is not appreciably absorbed and
should only be used to treat C. difficile colitis if metronidazole cannot be utilized. The
parenteral formulation is not excreted into the bowel and therefore cannot be used to
treat C. difficile colitis.
A. Criteria for vancomycin use:
1. For treatment of serious infections due to beta-lactam resistant gram-positive
microorganisms. Clinicians should be aware that vancomycin may be less rapidly
bactericidal than beta-lactam agents for beta-lactam susceptible staphylococci.
2. For treatment of infections due to gram-positive microorganisms in patients with serious
allergy (ie. anaphylaxis) to beta-lactam antimicrobials.
3. When antibiotic-associated colitis (AAC) fails to respond to metronidazole therapy or if
AAC is severe and potentially life-threatening, the use of oral vancomycin is acceptable.
The standard dose is 125 mg QID.
4. Prophylaxis, as recommended by the American Heart Association, for endocarditis
following certain procedures in patients at high risk for endocarditis.
5. Empiric treatment of presumed nosocomial infection due to gram-positive cocci (such
as patients with indwelling catheters) until results of cultures are known.
B. Situations in which the use of vancomycin is discouraged:
1. Routine prophylaxis for surgical patients, very low birth-weight infants, and patients on
continuous ambulatory peritoneal dialysis. Patients with a history of nonlifethreatening allergic reactions to penicillins can be safely prescribed
cephalosporin antibiotics as an alternative.
2. Empiric antimicrobial therapy for a febrile neutropenic patient, unless there is strong
evidence at the outset that the patient has an infection due to gram-positive
microorganisms (e.g., inflamed exit site of Hickman catheter).
3. Treatment in response to a single blood culture positive for coagulase-negative
staphylococcus, if other blood cultures drawn in the same time frame are negative, i.e.,
if contamination of the blood culture is likely.
4. Continued empiric use for presumed infections in patients whose cultures are negative
for beta-lactam-resistant gram-positive microorganisms.
5. Eradication of methicillin-resistant Staphylococcus aureus (MRSA) colonization.
6. Primary treatment of AAC.
17
VANCOMYCIN DOSING AND MONITORING GUIDELINES
1. Dosing for adults
The recommended dose of vancomycin is 15 mg/kg (based on actual body weight).
The dose should be rounded to the nearest 250 mg increment The dosing interval is
dependent upon the estimated creatinine clearance (Clcr)-see below. See section 2 on
page 14 for information on how to calculate creatinine clearance.
Clcr (ml/min)
> 90
70-89
46-69
30-45
20-29
< 20
Hemodialysis
Dose
15 mg/kg q12 hrs
15 mg/kg q18 hrs
15 mg/kg q24 hrs
15 mg/kg q36 hrs
15 mg/kg q48 hrs
q 3-7 days depending on levels
See section 2B
2. Monitoring
A. Vancomycin peak and trough levels have not been correlated with either efficacy or toxicity.
Therefore, peak and trough levels are generally not indicated. However, consideration
may be given to obtaining a vancomycin trough level if the following conditions are present:
1.
2.
3.
4.
Patients receiving vancomycin plus an aminoglycoside
Patients with rapidly changing renal function
Patients with central nervous system infections (meningitis)
Patients with endocarditis
Vancomycin trough levels can be obtained before the 4th dose in patients with normal renal
function. A serum creatinine should be obtained at least twice weekly for patients on
vancomycin therapy.
B. Hemodialysis
Consultation with nephrology or pharmacy is recommended.
1. High Flux Dialyzers
Administer 20 mg/kg as a single loading dose followed by 8 mg/kg after each
hemodialysis session
2. Conventional Dialyzers
Administer 20 mg/kg as a single loading dose. Further doses of vancomycin will
depend upon serum levels.
C. Peritoneal Dialysis
1. Vancomycin may be administered intraperitoneally (IP). Consultation with
nephrology is recommended.
18
GUIDELINES FOR CRITERIA BASED ANTIBIOTICS
•
•
•
•
•
•
Azithromycin
Cefotetan
Ceftriaxone
Levofloxacin
Norfloxacin
19
19
20
20
21
22
22
AMPICILLIN / SULBACTAM
Ampicillin / sulbactam is ampicillin combined with sulbactam which is an inhibitor of
microbial beta-lactamase. This spectrum of activity includes beta-lactamase producing
strains of E. coli, Klebsiella species, and Bacteroides species. Ampicillin-sulbactam is
not active against
P. aeruginosa. The standard dose is 3 grams q6h.
A. Criteria for ampicillin / sulbactam use:
1. Empiric therapy of community-acquired intra-abdominal infection of moderate
severity
2. Type II diabetic foot infections
3. Inpatient treatment of pelvic inflammatory disease with doxycycline
4. Postoperative pelvic cellulitis
5. Mild postpartum endometritis
6. Pre-operative prophylaxis for bowel, biliary, or gynecologic surgery (single
dose)
B. Situations in which ampicillin / sulbactam use is discouraged:
1. Nosocomial or severe community-acquired intra-abdominal infections
2. Infections not involving the gastrointestinal tract or pelvis such as pneumonia,
cellulitis, and urinary tract infections
3. Preoperative prophylaxis for abdominal hysterectomy or cesarean section
4. Postoperative prophylaxis
20
AZITHROMYCIN
Azithromycin is a macrolide (azalide) antibiotic with activity against Haemophilus influenzae,
Moraxella catarrahlis, and atypical pathogens such as Chlamydia pneumoniae, Chlamydia
trachomatis, Mycoplasma pneumoniae, and Legionella pneumophila. Azithromycin is active against
erythromycin susceptible Streptococcus pneumoniae and Staphylococcus aureus but erythromycin is
more active against these gram-positive cocci.
A. Criteria for oral azithromycin:
1. For the management of pulmonary infections caused by atypical pathogens. The standard
dose is 500 mg on day 1 followed by 250mg q24h on days 2-5.
2. For single dose therapy of Chlamydia trachomatis; one gram of azithromycin.
B. Criteria for intravenous azithromycin :
1. For the management of pulmonary infections caused by atypical pathogens in
patients who cannot take oral azithromycin. The standard dose is 500 mg q24h
intravenously followed by 500 mg q24h orally to complete a 7-10 day treatment course.
The timing of the switch to oral therapy should be done in accordance with clinical
response (see section 3 on page 63).
CEFOTETAN
Cefotetan is a 2nd generation cephalosporin (cephamycin) available only in intravenous form.
Concerns have arisen about hemolytic anemia and increasing resistance within anaerobic bacteria.
Therefore, caution should be used when considering cefotetan to treat community acquired intraabdominal infections, diabetic foot infections, pelvic inflammatory disease, postoperative pelvic
cellulitis, mild postpartum endometritis, and preoperative prophylaxis for bowel, biliary, or
gynecologic surgery.
The use of cefotetan is discouraged for nosocomial or severe community acquired intra-abdominal
infections, infections not involving the gastrointestinal tract or pelvis, preoperative prophylaxis for
abdominal hysterectomy or cesarean section, and postoperative prophylaxis.
21
CEFTRIAXONE
Ceftriaxone is a 3rd generation cephalosporin available only in parenteral form (IV or IM). It is
very active against most gram-negative bacilli excluding Pseudomonas aeruginosa. It is not
active against enterococci or anaerobes. The standard dose is 1 gram q24h.
A. Criteria for ceftriaxone use:
1. Documented infections due to susceptible:
a. gram-negative bacteria resistant to cefazolin, cefotetan, co-trimoxazole, or
ampicillin.
b. penicillin-resistant pneumococcus (life-threatening)
2. Empiric therapy for the following suspected infections until culture results are
available:
a. community acquired pneumonia (1 gm every 24 hours)
b. nosocomial pneumonia in patients who are non-hypotensive and not in intensive
care setting
(1gm every 24 hrs)
c. serious community-acquired and nosocomial infections when aminoglycoside or
co-trimoxazole therapy is inappropriate (1gm every 24hrs)
d. community-acquired meningitis (2gm every 12 hrs)
e. suspected sepsis in newly admitted pediatric patients > 3 months old and
suspected occult bacteremia in outpatients 3 to 36 months old
f. uncomplicated gonococcal infection or ambulatory management of PID
(250 mg IM x 1)
g. primary peritonitis (1gm every 24 hrs)
B. Situations in which ceftriaxone use is discouraged
1.
2.
.
4.
Suspected or documented gram-positive infections
Infections due to Enterobacter sp.
Endocarditis
Continued empiric use:
a. when infectious etiology is not felt to be the cause of fever or
b. when cultures are positive for organisms sensitive to more narrow spectrum
antibiotics or
c. when patient is able to take an oral antibiotic
5. Empiric use for patients in septic shock or located in intensive care units.
6. Empiric use for febrile neutropenic patients
22
LEVOFLOXACIN
Levofloxacin is a quinolone antibiotic with enhanced activity against gram-positive
microorganisms. It is more active than ciprofloxacin against S. pneumoniae.
Levofloxacin is active against atypical pathogens such as M. pneumoniae, C.
pneumoniae, and L. pneumophila. Levofloxacin is also active against gram-negative
bacilli including P. aeruginosa.
I. Potential indications for levofloxacin use
A. Community acquired pneumonia
B. Nosocomial pneumonia
II. Dosing Guidelines
A. Usual dosing for patients with a creatinine clearance > 50 ml/min. For
patients with a lower calculated creatinine clearance please refer to page 71.
Indication
Dose
1. Community acquired pneumonia
2. Nosocomial pneumonia
500 mg IV / PO q24h
750 mg IV / PO q24h
NORFLOXACIN
A. Criteria for norfloxacin use:
Norfloxacin is a quinolone antibiotic with activity against gram-negative pathogens
which includes P. aeruginosa. Norfloxacin is indicated for the treatment of infections
confined to the urinary tract. Norfloxacin does not produce blood levels high enough to
treat bacteremic patients.
1. For treatment of complicated cystitis and prostatitis in patients unable to take
co-trimoxazole. The dose is 400 mg po bid.
23
GUIDELINES FOR CONTROLLED ANTIBIOTICS
•
•
•
•
Ceftazidime
Ciprofloxacin
Meropenem
24
24
25
26
27
CEFTAZIDIME
Ceftazidime is a third generation cephalosporin. It is the most active cephalosporin against
P. aeruginosa. The activity of ceftazidime against gram-positive cocci and anaerobes is poor.
For the treatment of P. aeruginosa infections, it is generally recommended that ceftazidime
be combined with an aminoglycoside. The decision to add an aminoglycoside for synergy
should be based on a risk versus benefit decision. The potential advantage of the
combination (synergistic killing coupled with the potential for decreased bacterial resistance)
must be weighed against the potential nephrotoxicity and ototoxicity of the aminoglycoside.
I. Potential indications for ceftazidime use
A. Therapy for documented Pseudomonas aeruginosa infections
B. Empiric therapy for hospital / nursing home acquired infections such as:
•
•
•
•
Nosocomial bacteremia
ICU acquired pneumonia or other infection
Septic shock
Cystic fibrosis
C. Empiric therapy in febrile neutropenic patients who do not have a serious allergy
(anaphylaxis) to penicillin. If the allergy to penicillin is a rash, ceftazidime may be
safely used.
II. Situations in which ceftazidime use is discouraged
A. Treatment of non-pseudomonal gram-negative or gram-positive infections
B. Empiric treatment of community acquired infections
III. Dosing guidelines
A. Usual dosing for patients with creatinine clearance > 50 ml/min. For patients with a
lower calculated creatinine clearance please refer to page 71.
Indication
Dose
1. Life threatening infections such as pneumonia, ....................2 g q8h
bacteremia, neutropenia
2. Urinary tract infections...........................................................500 mg 12h
3. Other systemic infections ......................................................1-2 gm q8h
25
CIPROFLOXACIN
Ciprofloxacin is a second generation quinolone with excellent activity against aerobic gramnegative rods including Pseudomonas aeruginosa. Activity against staphylococci and
streptococci is less than levofloxacin and trovafloxacin. Ciprofloxacin has no activity against
anaerobes. The oral absorption of ciprofloxacin is excellent. As a result, blood levels with the
intravenous and oral formulations are similar.
FAHC IS EXPERIENCING INCREASING CIPROFLOXACIN RESISTANCE IN
PSEUDOMONAS. THIS IS ESPECIALLY TRUE IN THE ICUs. CAUTION IS SUGGESTED.
I. Potential indications for ciprofloxacin use:
A. Therapy for documented Pseudomonas aeruginosa infections
B. Empiric therapy for hospital / nursing home acquired infections such as:
•
•
•
•
Nosocomial bacteremia
ICU acquired pneumonia or other infection
Septic shock
Intraabdominal infections in combination with an anti-anaerobe and
anti-enterococcal agent
C. Aerobic gram-negative rod bone infections
D. Documented infections due to Enterobacter species. TMP-SMX may be used as an
alternative to ciprofloxacin for infections due to Enterobacter species.
E. Type II and III diabetic foot infections in combination with an anti-anaerobe
II. Situations in which ciprofloxacin use is discouraged
A. Treatment of non-pseudomonal gram-negative (except Enterobacter species), grampositive, or anaerobic infections
B. Empiric treatment of community acquired infections except for type II and III diabetic
foot infections
A. Usual dosing for patients with creatinine clearance > 30 ml/min. For patients with a
lower calculated creatinine clearance please refer to page 71.
Indication
1.
2.
3.
4.
5.
Nosocomial pneumonia
Bone and joint
Intraabdominal
Skin and skin structure
Urinary tract
Intravenous Dose
400 mg q8h
400 mg q8-12h
400 mg q12h
400 mg q8-12h
200-400 mg q12h
26
Oral Equivalent
750 mg q12h
500-750 mg q12
500 mg q12h
500-750 mg q12
250-500 mg q12
PIPERACILLIN / TAZOBACTAM
Piperacillin / tazobactam is piperacillin combined with tazobactam which is an inhibitor
of microbial beta-lactamase. This spectrum of activity includes beta-lactamase
producing strains of E. coli, Klebsiella species, and Bacteroides species. The addition
of tazobactam does not enhance the activity of piperacillin against Pseudomonas
aeruginosa.
I. Potential indications for piperacillin / tazobactam use
A. Nosocomial intraabdominal or pelvic infections in patients who are critically ill
or in the intensive care unit.
B. Type II and III diabetic foot infections
C. Nosocomial pneumonia
II. Situations in which piperacillin / tazobactam use is discouraged
A. Empiric treatment of community acquired infections
B. Type I diabetic foot infections
III. Dosing Guidelines
A. Usual dosing for patients with creatinine clearance > 50 ml/min. For patients
with a lower calculated creatinine clearance please refer to page 71.
Indication
Dose
1. Intraabdominal infections
and diabetic foot infections
3.375 gm q6h
2. Nosocomial pneumonia
4.5 gm q6h
27
MEROPENEM
Meropenem is a carbapenem antibiotic with broad activity against aerobic gram
negative rods including Pseudomonas, anaerobes, and gram positive bacteria
including streptococci, staphylococci and enterococci.
I. Potential indications for meropenem use
A. Nosocomial polymicrobial infections
Intra-abdominal sepsis
Complex gynecological infections (page 45)
B. Treatment of Pseudomonas
C. Infections in patients with cystic fibrosis
D. Type III diabetic foot infections
E. Necrotizing fasciitis
II. Situations in which meropenem use is discouraged
A. Community acquired infections
B. Infections caused by a single type of bacteria
Pneumonia
Cellulitis
UTI
A. Usual dosing for patients with creatinine clearance > 50 ml/min. For patients
with a lower calculated creatinine clearance please refer to page 71.
Indication
1.
2.
3.
Dose
Most indications
Pseudomonas infections
Meningitis
1g q8h
2g q8h
2g q8h
28
TREATMENT GUIDELINES AND ALGORITHMS FOR SPECIFIC INFECTIONS
Community and nosocomial / nursing home acquired pneumonia .... 29-32
Intra-abdominal infections .................................................................. 33-37
Urinary tract infections ....................................................................... 38-39
Diabetic foot infections ....................................................................... 40-41
Fever and neutropenia ....................................................................... 42-43
Female genital tract infections ........................................................... 44-45
Bite wound infections ......................................................................... 46-47
Infectious Diarrhea & C. difficile ......................................................... 48-52
Principles of surgical prophylaxis ....................................................... 53-55
Prevention of bacterial endocarditis ................................................... 56-58
Therapy for selected sexually transmitted diseases .......................... 59-60
Post-exposure prophylaxis................................................................. 61
29
COMMUNITY-ACQUIRED AND NOSOCOMIAL / NURSING HOME PNEUMONIA
1.
A sputum gram stain & culture should be obtained in all patients with suspected pneumonia.
2.
Most cases of community acquired pneumonia (CAP) are due to S. pneumoniae, Haemophilus
influenzae, Moraxella Catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae, and
Legionella species. Gram negative bacilli are uncommon pathogens except in nursing home
patients. See Figures 1 and 2.
3.
For community-acquired pneumonia, a legionella urinary antigen should be obtained.
4.
Aspiration pneumonia occurring in the community is generally due to oral anaerobes and can be
treated with clindamycin monotherapy. In contrast, aspiration pneumonia occurring in the
hospitalized patient is generally due to gram-negative organisms.
5.
Most cases of nosocomial pneumonia ( > 48 hours in hospital) are due to gram-negative
organisms. Approximately 20-25 % of nosocomial pneumonias are due to Staphylococcus and
Streptococcus. Pneumonia acquired in skilled nursing facilities should be considered
nosocomial. Pneumonia acquired in the ICU should be considered due to Pseudomonas
aeruginosa until proven otherwise. See Figure 3.
6.
Regarding hospital acquired pneumonia and ventilator associated pneumonia:

Narrow the initial broad spectrum antibiotics to a single agent based on culture and
sensitivity.

There is no data supporting the use of two antibiotics to treat pneumonia due to
Pseudomonas. Using two antibiotics has not been shown to improve outcomes or prevent
resistance.

Negative sputum cultures (if obtained while the patient has not had a change in antibiotics
for the past 72 hours) can be used to discontinue antibiotics.

Limit the duration of therapy to 7 days unless Pseudomonas is isolated. If Pseudomonas is
isolated, treat for 14 days.
30
COMMUNITY-ACQUIRED PNEUMONIA
OUTPATIENT THERAPY
Figure 1
SYMPTOMS (+)
CHEST X-RAY(+)
Sputum Gram stain
& culture
Not Available
Alternatives
Preferred
Cefpodoxime 1
or
Amoxicillin /
clavulanate 1
Macrolide 2
or
Doxycycline
or
Levofloxacin
1
No activity against atypical pathogens
2
Erythromycin, azithromycin, clarithromycin
31
COMMUNITY-ACQUIRED PNEUMONIA REQUIRING
HOSPITALIZATION
Figure 2
SYMPTOMS (+)
CHEST X-RAY (+)
SPUTUM GRAM STAIN
SPUTUM & BLOOD CULTURES
(-) If not diagnostic
Levofloxacin
or
Ceftriaxone
+
Azithromycin
Adjust antibiotics based
on culture & sensitivity
Transition to oral
antibiotics
If cultures not available
Levofloxacin
or
Cefpodoxime
+
Azithromycin
32
NOSOCOMIAL PNEUMONIA
Figure 3
SYMPTOMS (+)
CHEST X-RAY (+)
Risk Factors for Multi-Drug Resistant Pathogens?

Antibiotic therapy within preceding 90 days
Hospitalization > 5 days
Hospitalization within previous 90 days
Residence in nursing home
Chronic dialysis
Home wound care
Immunosuppressed
Yes
No
Ceftriaxone
or
Levofloxacin
Ceftazidime or Cefepime or Meropenem or Pip-tazobactam
+
Ciprofloxacin or Levofloxacin
+/Vancomycin
(If gram-positive cocci are present on sputum gram-stain)
Narrow spectrum to a single agent
based on culture and sensitivity
Negative sputum cultures (if obtained while
the patient has not had a change in antibiotics
in the past 72 hours) can be used to
discontinue antibiotics.
Treat for 7 days. If
Pseudomonas, treat for 14 days.
Reference: American Thoracic Society. Guidelines for the
Management of Adults with Hospital-acquired, Ventilatorassociated, and Healtcare-associated Pneumonia. Am J Respir
Crit Care Med vol 171. pp 388-416, 2005.
33
ABDOMINAL INFECTIONS
1.
Intra-abdominal infections (IAI) include localized peritonitis (see figure 1) such as
cholecystitis/cholangitis, diverticulitis, appendicitis, and/or diffuse peritonitis
2.
Diffuse Peritonitis can be defined as:
• Primary (spontaneous bacterial peritonitis or SBP)-See figure 2
-associated with ascites secondary to cirrhosis
-peritoneal fluid with > 250 neutrophils/ml
-usually monobacterial
• Secondary
(See figure 3)
- result of perforation of gastrointestinal tract
- polymicrobial in nature
- need to treat for both aerobic and anaerobic gram-negative bacteria
- need surgery consult
• Tertiary
-persistent infection in seriously ill patients with secondary peritonitis
3.
Community-acquired IAI is usually caused by both aerobic gram-negative bacteria (most
commonly E. coli but also Proteus and Klebsiella species) and anaerobic gram-negative
bacteria (most commonly Bacteroides species). It is not necessary to treat communityacquired IAI with antibiotics with activity against Pseudomonas, Enterobacter, or
Enterococcus species.
4.
Nosocomial IAI may be caused by more drug resistant gram-negative bacteria such as
Pseudomonas, Enterobacter, and Enterococcus due to changes in bacterial flora that
occur in an institutional setting. More broad spectrum agents and synergistic
combinations may be necessary to treat these infections effectively.
5.
Cultures are not needed routinely for community-acquired secondary peritonitis. If
cultures are obtained, the microbiology laboratory will perform a limited evaluation unless
consulted by the clinician. Fluid or tissue specimens in an anaerobic transport vial should
be collected for complicated or tertiary peritonitis and for localized abscesses.
6.
See table on page 37 for activities of antimicrobial agents used to treat intra-abdominal
infections
34
LOCALIZED PERITONITIS
Figure 1
Suspect Localized Infection
- Diverticulitis
-Female genital tract (pg 44-45)
-Appendicitis
- Cholangitis / cholecystitis
Mild Diverticulitis
Admit To Hospital
Treat as Out-Patient
Surgery Consult
ORAL ANTIBIOTICS
Co- Trimoxazole +
Anti-anaerobe*
or
Cefpodoxime +
Anti-anaerobe
or
Amoxicillin/
clavulanic Acid
or
Ciprofloxacin +
Anti-anaerobe
Moderate
(Non-ICU floor)
or
Severe
(ICU)
Ceftriaxone +
Metronidazole +
Ampicillin
or
Ceftriaxone + Metronidazole
or
Treat Until
Symptoms
Resolved
Ciprofloxacin +
Metronidazole +
Ampicillin
Ciprofloxacin + Metronidazole
or
or
Meropenem
35
PRIMARY PERITONITIS
Figure 2
SUSPECT
SBP
-Abdominal Pain, Fever
-Mental Status Changes
-Leukocytosis
PARACENTESIS
-Cell Count, Differential
-Send Peritoneal Fluid for Gram Stain
-Inject Peritoneal Fluid Into Both Blood
Bottles
PMN > 250/mm
CEFTRIAXONE
1gm QD
ADJUST ANTIBIOTICS
BASED ON CULTURE
RESULTS
36
Figure 3
SECONDARY PERITONITIS
COMMUNITY-ACQUIRED
NOSOCOMIAL
ADMIT TO HOSPITAL
Blood Cultures
SURGERY CONSULT
Submit Fluid in
Sterile Container
For Culture
SURGERY CONSULT
Peritoneal Culture
Not Routinely
Required
MODERATE
(NON-ICU FLOOR)
SEVERE
(ICU)
NON-ICU
FLOOR
Ampicillin-sulbactam
or
Ceftriaxone + metronidazole
or
Ceftriaxone + metronidazole + ampcillin
or
Ciprofloxacin + metronidazole + ampicillin
or
Ciprofloxacin + metronidazole
or
Meropenem
37
ICU
RELATIVE ACTIVITIES OF ANTIMICROBIAL AGENTS
USED TO TREAT INTRA-ABDOMINAL INFECTIONS
Aminoglycoside
Ampicillin
Ceftazidime
Cefotetan
Ceftriaxone
Ciprofloxacin
Clindamycin
Co-trimoxazole
Meropenem
Metronidazole
Non-Pseudomonas
Gram-Negative
Aerobes
+++
+
++
+++
++
++
+++
++
+++
-
Piperacilin
Piperacillin /
tazobactam
Vancomycin
Amoxicillin /
clavulanate
Cefpodoxime
+
++
+++
Gram-Negative
Anaerobes
Psudomonas
aeruginosa
++
++
+++
+++
+++
+++
Enterococcus
++
++
+++
+++
-
-
+++
+++
+++
++
++ (use
w/aminoglycoside)
++ (use
w/aminoglycoside)
-
++
++
---
+++
++
---
---
---
No activity
Limited activity
Moderate activity
High activity
38
++
++
+
++
++
++
URINARY TRACT INFECTIONS
1.
Urine culture can be ordered by three methods:
• For most cases, order culture only if urinalysis is abnormal.
• Order culture and urinalysis together for symptomatic patients who may not have
pyuria (ie. neutropenic patients).
• Order culture alone for post-treatment ‘test of cure’, routine pregnancy screening, or
prior to urologic procedure.
2.
A urinary tract infection is generally defined by the presence of pyuria. Pyuria is defined as
greater than 5 WBC’s on microscope or (+) leukocyte esterase.
3.
Bacteriuria without signs or symptoms of UTI should not be treated except for:
• Pregnant women
• Prior to a urologic procedure
• Renal transplant patients
4.
Elderly patients (>65 years) without signs or symptoms of UTI should not be cultured or treated.
Asymptomatic bacteriuria or pyuria is not an indication for treatment.
5.
Patients with an indwelling catheter without signs or symptoms of UTI should not be cultured or
treated. Asymptomatic bacteriuria or pyuria is not an indication for treatment.
6.
Candiduria in catheterized patients does not need to be treated in most cases. Candiduria
usually represents colonization, not infection, in these patients. The best approach to eliminate
candiduria is to remove the catheter.
7.
Recommended empiric antibiotic regimens in order of appropriateness:
a. Uncomplicated cystitis in females
Cost
1. Co-trimoxazole DS po bid x 3 days..................................... $2.30
2. Nitrofurantoin 100mg po qid x 7 days ............................... $19.00
3. Fosfomycin 3 grams x1 dose ............................................ $26.00
4. Cephalexin 250mg po qid x 3 days ..................................... $8.00
b. Complicated cystitis
1. Co-trimoxazole DS po bid x 7 days
2. Norfloxacin 400mg po bid x 7 days
3. Cefpodoxime 100mg po bid x 7 days
c. Pyelonephritis
Outpatient
1. Co-trimoxazole DS po bid x 14 days
2. Cefpodoxime 200mg po bid x 14 days
3. Ciprofloxacin 500mg po bid x 14 days
Inpatient**
** Transition to oral antibiotics when stable for 24-48 hrs
1. Co-trimoxazole 160mg iv q12 hrs x 14 days
2. Gentamicin +/- ampicillin 1gm iv q6 hrs x 14 days
3. Ciprofloxacin 200mg-400mg iv q12 hrs +/- ampicillin 1gm iv q6 hrs x 14 days
39
MANAGEMENT OF URINARY TRACT INFECTIONS
NO
SYMPTOMATIC ?
NO Culture
NO Treatment
Except:
- pregnancy
- prior to urologic
procedure
- renal transplant
YES
URINALYSIS
microscopic or
dipstick
POSITIVE FOR
PYURIA ?
NO
YES
Does NOT have UTI
NO Culture
NO Treatment
Consider urethritis or
vaginitis
DETERMINE SEVERITY
UNCOMPLICATED
CYSTITIS IN FEMALES
COMPLICATED
CYSTITIS
young, healthy, sexually active,
without complications
symptoms > 7 days
abnormal anatomy
history of urologic surgery
history of renal stones
immunocompromised
diabetes mellitus
pregnancy
male patient
presence of catheter
NO culture
Antibiotics see 7a
NO followup culture
NO urologic evaluation
PYELONEPHRITIS
additional systemic
symptoms such as
fever and flank pain
Culture urine & blood
Antibiotics x 14 days
afebrile
24-48 hrs
Culture
Antibiotics see 7b
Followup culture
40
Transition to oral
antibiotics
Followup culture
DIABETIC FOOT INFECTIONS
(Special thanks to Dr. Ricci and Vascular Surgery)
1. Soft tissue and bone infection of the lower extremity is the most common cause for hospital
admission
2. Usually occur on pressure points of the foot (first metatarsal head)
3. Most diabetic foot infections are polymicrobial (gram-negative rods, anaerobes, and enterococci).
This is especially true in type II and III infections-see below.
4. Culture purulent drainage, abscess, or tissue from deep debridement. Do not culture superficial
ulcers.
5. Severity of infection is based on clinical exam:
• Type I (mild)
- Superficial ulceration
- Mild erythema of skin
- No osteomyelitis
- No systemic toxicity
- Generally caused by staphylococci and streptococci
- Can be treated with oral antimicrobials
• Type II (moderate or limb threatening)
- Ulceration to deep tissues
- Cellulitis around chronic ulcer
- Osteomyelitis may be present
- May be draining purulent material
- Generally polymicrobial
- Generally need surgical debridement and intravenous antibiotics
• Type III (Severe or limb and life threatening)
- Ulceration to deep tissues
- Cellulitis
- Osteomyelitis usually present
- Systemic toxicity
- Necrosis/gangrene
- Polymicrobial
- Need urgent surgical debridement, drainage, or amputation
- Intravenous antibiotics
6. Signs of peripheral vascular obstruction
Consult vascular surgery if present:
- Claudication
- Absent pulses
- Chronic foot pain
- Dependent rubor
If the above clinical signs are present, consider work-up with the following:
Pulse volume recording (PVR)
Ankle-brachial Index (ABI)
41
MANAGEMENT OF DIABETIC FOOT INFECTIONS
Clinical Assessment of Infection
-Degree of erythema/ purulence
-Depth of ulcer
-Exposed bone
-Extent of necrosis / gangrene
)
-Toxicity of patient (fever, leukocytosis)
Peripheral Vascular Obstruction
X-ray to assess for osteomyelitis especially
ftype II and III
i f i
-PVR
-ABI (< 0.7)
Angiogra
-
Type I (Mild)
Oral Antibiotics
-Dicloxacillin 500 mg q6
or
-Cephalexin 500 mg q6h
Type II (Moderate)
-ID / Surgery
-ID / Surgery
Consultation
-Debridement
Consultation
-Debridement
Admit for IV Antibiotics
-Ampicillin / sulbactam
or
-Ceftriaxone + clindamycin
+/- ampicillin
or
-Clindamycin 300 mg q6h
Type III (Severe)
Admit for IV Antibiotics
-Ceftazidime + clindamycin
+ Ampicillin
or
-Ciprofloxacin + clindamycin
+ Ampicillin
or
-Ciprofloxacin
+ clindamycin
+/- ampicillin
or
-Piperacillin / tazobactam
or
or
-Piperacillin / tazobactam
42
-Meropenem
FEVER AND NEUTROPENIA *
1.
Neutropenia is defined as an absolute neutrophil count (ANC) less than 500/mm3
(some authorities use 1000/mm3 as breakpoint). ANC can be calculated as: ANC
= WBC x (% PMNs + % Bands). Fever in a neutropenic patient is defined as
temperature > 38.0°C on two occasions or over 38.3°C at any time.
2.
Initial empiric antibiotic therapy assumes there is an infection due to aerobic gramnegative bacteria, which is associated with significant mortality in the neutropenic
patient. It is not necessary to treat initially for a gram-positive bacterial infection
unless there is evidence of a central line infection or cellulitis.
3.
Monotherapy with ceftazidime or cefepime has been shown to be as efficacious as
ceftazidime + aminoglycoside or cefepime + aminoglycoside. If the patient has a
cephalosporin allergy, infectious disease consultation is suggested.
4.
Risk of infection can vary in patients with fever and neutropenia and depends on
depth and duration of neutropenia, type of malignancy (ie. Leukemia vs solid
tumor), and other co-morbid conditions.
5.
Patients with neutropenia have an impaired inflammatory response, therefore they
may not have typical signs or symptoms of infection.
6.
Patients with intravenous catheters should have blood cultures obtained from each
port and from a peripheral site prior to initiation of antimicrobial therapy.
7.
Use of prophylactic antibacterials, anti-fungals or anti-viral agents is not
recommended.
An Infectious Disease consultation is recommended for all patients with
neutropenic fever especially those with the following conditions:
•
•
•
•
•
Pulmonary infiltrate
Central catheter infection
Intra-abdominal infection
Suspected fungal infection
Fever greater than 3 days
2002 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with
Cancer. Infectious Diseases Society of America. Clinical Infectious Diseases
2002;34:730-51.
43
MANAGEMENT OF FEVER AND NEUTROPENIA
Blood Cultures x 2
Chest X-Ray
Order Urinalysis and
Urine Culture Together
PROMPTLY START
EMPIRIC ANTIBIOTICS
Ceftazidime or Cefepime or Meropenem
Add Vancomycin for:
♦
♦
♦
♦
♦
1 – 3 days
After 3 days
AFEBRILE
FEBRILE
CONTINUE
ANTIBIOTICS
NO EVIDENCE
OF
INFECTION +
ANC > 500
Consider switch
to oral
ciprofloxacin
“STABLE”
NO EVIDENCE
OF INFECTION +
ANC > 500
catheter infection
cellulitis
if on ciprofloxacin prophylaxis
(+) blood cultures with gram positive bacteria
if hypotensive
DIFFERENTIAL DIAGNOSIS
♦
♦
♦
♦
♦
♦
♦
INFECTION
IDENTIFIED
D/C
ANTIBIOTICS
IF AFEBRILE
5-7 DAYS
Resistant gram-negative bacteria
Gram-positive infection
Infected catheter
Anaerobic infection
Drug allergy
Viral illness
Non-infectious ethiology
“UNSTABLE”
ANC < 500
INFECTIOUS
DISEASE
CONSULTATION
STRONGLY
ENCOURAGED
D/C
ANTIBIOTICS
after 7 DAYS
44
FEMALE UPPER GENITAL TRACT INFECTIONS
1.
Female upper genital tract infections (UGTI) covered by these guidelines include
postpartum endometritis, postoperative pelvic cellulitis, acute salpingitis, and pelvic
abscess.
2.
The usual pathogens isolated from patients with UGTI are sexually transmitted
pathogens and endogenous organisms that originate from the normal vaginal flora (see
below).
3.
UGTIs are usually polymicrobial. Anaerobic bacteria predominate numerically and are
virtually always present in pelvic abscesses. Multiresistant gram-negative aerobic
bacteria are usually not present unless the patient has recently received antibiotics or has
undergone prolonged hospitalization. Enterococci are generally not primary pathogens,
but may become secondary invaders, accounting for some failures of initial therapy.
4.
Gynecologic consultation for all patients admitted with UGTI is recommended.
5.
Unless otherwise stated, antimicrobial therapy should be continued until the patient’s
temperature has been below 37.5C for 24 hours, she is pain free, and the white blood cell
count is normal.
For patients with suspected pelvic abscess, potent antianaerobic antibiotic coverage
must be included. Drainage (via laparoscopy, laparotomy, or percutaneous catheter) may
be necessary. In general, the larger the abscess the less likely it will respond to
antimicrobial therapy alone. Abscesses less than 4-5 cm usually respond without
drainage, while those larger than 8-10 cm usually require concomitant drainage.
USUAL PATHOGENS RECOVERED FROM UGTI
Exogenous:
Neisseria gonorrhoeae, Chlamydia trachomatis, Streptococcus group A
(rare), Mycobacterium tuberculosis (rare)
Endogenous:
Anaerobic: Peptostreptococcus, Bacteroides fragilis group, Prevotella sp, Clostridium
sp, Fusobacteria, Actinomyces (IUD infections), Eubacterium (IUD
infections)
Aerobic:
Streptococcus (groups B, D, and others), Escherichia coli, Klebsiella sp,
Gardnerella vaginalis, Mycoplasma hominis
45
FEMALE UPPER GENITAL TRACT INFECTION
SUSPECT POSTOPERATIVE
PELVIC CELLULITIS OR
POSTPARTUM ENDOMETRITIS
SUSPECT
ACUTE PID
Endocervical
Culture or Probe
for Gonorrhea and
Chlamydia
MILD
BEGIN EMPIRIC
THERAPY
OUTPATIENT*
INPATIENT*
or
Gentamicin
+
Clindamycin
Ceftriaxone
250mg IM x1
+
Doxycycline
100mg BID x 14 days
Cefotetan
2gm IV q12 hrs
until improved
+
Doxycycline
100mg bid x 14 days
or
or
Meropenem
or
Gentamicin
+
Clindamycin
or
Ampicillin / Sulbactam 3g q6h
+
Doxycycline 100mg BID
*Reference:
Gentamicin
+
Anti-anaerobe**
+
Ampicillin
Ceftriaxone
+
Anti-anaerobe**
+
Ampicillin
or
Ofloxacin
400mg BID x 14 days
+
Metronidazole
500mg BID x 14 days
SEVERE
2002 Sexually Transmitted Diseases Treatment
Guidelines MMWRVol. 51, No. RR 06, May 10, 2002.
** Anti-anaerobe : Metronidazole or Clindamycin
46
BITE WOUND INFECTIONS
Each years several million Americans are bitten by animals resulting in approximately 300,000 visits to
emergency departments, 10,000 hospitalizations, and 20 deaths. Ninety percent of these bites are from cats
and dogs of which 3 to 18 percent of dog bites and 28 to 80 percent of cat bites eventually become infected.
1. Animal and human bite wounds are polymicrobial:
Animal: Pasteurella, Staphylococci and streptococci, and anaerobes
Human: Staphylococci, streptococci, and anaerobes
2. Bite wounds have the potential to inoculate deep tissue spaces and joints.
3. The following types of wounds are associated with a HIGH RISK of complications:
• Bites from cats and humans
• Bites to the hand, below the knee, or over a joint
• Bite wounds greater than 6-12 hours old
• Bite wounds occurring in the elderly, diabetics, or in individuals with prosthetic heart valves
or who are immunocompromised
Bite wound management:
• Aggressive local wound care (clean, debride, irrigate)
• See flow diagram for antibiotics
• The following wounds are generally not sutured:
- Wounds which are not disfiguring
- Punctures
- Human or cat bites
- Bites to the extremities
- Wounds which are greater than 6-12 hours old
5. Consider the risk of tetanus
• Give tetanus booster if original three dose series has been given, but none
in the past 5 years. Give a primary series and tetanus immunoglobulin if patient
was never immunized.
6. Consider the risk of rabies
a. Investigate the circumstances surrounding the bite and make a decision for the need for rabies
vaccination in conjunction with the CDC Rabies Hotline (1-800-Rabies).
b. Notify the Vermont Department of Health (Tele # 863-7323)
c. Attempt to find, investigate and quarantine all domesticated unvaccinated animals for ten days.
Treat patient if animal becomes ill.
d. Bites from untraceable domesticated animals require initiation of rabies vaccination
e. Bites from untraceable wild carnivores or bats require initiation of rabies vaccination
f. Significant exposure to the saliva of a potentially rabid animal even without a bite may require
vaccination. Call the Vermont Department of Health with questions (Tele # 863-7323).
g. BATS are assumed to be rabid. Bites from rabbits, mice, rats, squirrels, hamsters and guinea pigs
almost never call for antirabies prophylaxis.
h. If vaccination is required, one dose of the human rabies immunoglobulin (HRIG) and a total of five
doses of the human diploid cell rabies vaccine (HDCV) are given as follows:
Dose
HRIG
20 IU/kg
HDCV
1 ml
Route
If anatomically feasible, the full dose should be
infiltrated around the wound(s) and any
remaining volume should be administered IM at
an anatomic site distant from vaccine
administration.
IM injection in deltoid area only
47
Time
Day 0
Days 0, 3, 7, 14, 28
MANAGEMENT OF BITE WOUND INFECTIONS
Identify Circumstances
-Human vs Animal
-High risk patients (see #3)
-Rabies risk
Clean, Irrigate, Debride
-Neurovascular function
-Culture if purulent
-Suture (see #4)
Consider for all patients
requiring hospital
admission
Consider
Vaccination
Consultation
1. Tetanus (see #5)
1. Surgery
Antibiotics
2. Rabies (see #6)
-Orthopedics for hand/joint
High risk
non-infected wounds
2. Infectious Disease
Infected wounds
Therapy
Prophylaxis
(10-14 days)
(3-5 days)
Primary
Alternative
Parenteral
Parenteral
*
* If < 8 years, use TMP/SMX
** If < 18 years, use TMP/SMX
Ampicillin / sulbactam 1.5 g q6h
OR
Ceftriaxone 1g q24h
+
Clindamycin 600mg q8h
Oral
Amox/ calvulanate 500mg TID
48
Doxycycline 100 mg q12h
+
Clindamycin 600 mg q8h
OR
Ciprofloxacin** 400 mg q12h
+
Oral
Doxycycline*
100 mg q12h
+
Clincamycin 300mg q6h
OR
Ciprofloxacin**
500 mg q12h
+
INFECTIOUS DIARRHEA
Gastroenteritis, a term generally used to describe diarrhea with vomiting and abdominal pain,
often is due to non-inflammatory infections, but similar symptoms may be due to noninfectious causes. Food-borne disease frequently causes upper gastrointestinal symptoms
after a short incubation period, especially from ingestion of pre-formed bacterial toxins (e.g.
Staphylococcus aureus and Bacillus cereus). Dysentery is a constellation of symptoms due to
infection with an invasive colonic pathogen and includes small-volume stools containing blood
and mucus, usually in association with fever and severe abdominal cramping.
Most infectious diarrheas are acquired through fecal-oral transmission of pathogens from
water, contaminated food, or via person-to-person contact. These infections are:
• common and often self-limited illness.
• often more severe in the elderly.
• more often seen in those with international traveler, those exposed to day care
centers, immune compromised hosts, hospitalized patients and those engaging in
oral-anal sexual practices.
• often non-diagnosed (81% of cases of food-borne disease)
• commonly due to Norwalk and Norwalk-like viruses
• due to Campylobacter, Salmonella, Shigella and Clostridium perfringens (90% of
diagnosed cases of food borne diarrheal illnesses)
Table 1: Incubation period, Symptoms and Pathogens
Incubation
Common symptoms
1-6 hours
Nausea, vomiting
8-16 hours
Abdominal cramps,
diarrhea
Nausea, vomiting,
diarrhea, descending
paralysis
Fever, abdominal
cramps,
diarrhea
8-16 hours
16-48 hours
16-72 hours
Associated pathogens and
toxins
Pre-formed toxins of Bacillus
cereus and Staphylococcus
aureus
Preformed toxins of C.
perfringens, B. cereus
Clostridium botulinum toxin
Salmonella, Shigella,
Campylobacter,
Vibrio parahemolyticus, Yersinia
enterocolitica
ETEC , V. cholera and
parahemolyticus,
Campylobacter, Salmonella,
Shigella, Listeria
Norwalk and Norwalk-like viruses
Abdominal cramps,
watery diarrhea
24-48 hours
Gastroenteritis,
headache
72-120 hours
Bloody diarrhea
E.coli 0157:H7
ETEC = enterotoxigenic E.coli, E.coli 0157:H7 = enterohemorrhagic E.coli.
49
Table 2: History and Epidemiologic Clues
History and Epidemiology
History
• antacid or H2 blocker use
• recent antibiotic use/hospitalization
• chronic care facilities
• liver disease
Epidemiologic risks
• travel to a developing region
•
travel to mountainous areas
•
contact with children in diapers
•
•
male homosexual
diarrhea after social gathering
Pathogens
•
•
•
•
Increased risk for all enteric pathogens
C.difficile
C.difficile, Aeromonas, viral pathogens
Vibrio spp.
•
Enterotoxigenic E.coli, Shigella, Salmonella,
Campylobacter, Giardia, Cholera
Giardia, Cyclospora
Cryptosporidium, Giardia,Campylobacter,
Shigella, Rotavirus, Norwalk virus
HSV, N.gonorrhea, Campylobacter, Amebiasis
Salmonella, Campylobacter, Norwalk virus,
Bacillus cereus, Clostridium perfringens
Yersinia enterocolitica
Vibrio parahaemolyticus
•
•
•
•
•
contact with domestic and agricultural •
animals
• consumption of raw and undercooked
shellfish
HSV = herpes simplex virus, H2 = type 2 histamine
•
Table 3: Diarrhea Syndromes
Syndrome
Acute watery
diarrhea
Colitis, dysentery
Proctitis
Common symptoms
Location
Small intestine
• large volume
stools
• cramps
Colon
• frequent, small
stools
• tenesmus
• blood and mucus
• fever, cramps
Rectum
• same as colitis
Persistent
(>14days) and
Chronic
(> 4 weeks)
diarrhea
•
•
Small intestine
variable, usually
and/or colon
watery diarrhea.
may have signs of
weight loss
vitamin deficiency
Gastroenteritis
(food-borne)
•
•
vomiting, nausea
watery diarrhea
•
Stomach, small
bowel
Select microbial causes
Many non-inflammatory
enteric pathogens including
viruses, Giardia and ETEC
Shigella, Campylobacter,
Salmonella, E.coli 0157:H7,
EIEC, E. histolytica,
C. difficile
N. gonorrhea, herpes
viruses, Chlamydia
trachomatis, syphilis
Protozoa (Cryptosporidium,
Cyclospora, Isospora,
Microsporidum), EPEC.
Preformed toxins of S.
aureus, B. cereus, and viral
pathogens.
ETEC = enterotoxigenic E. coli, E.coli 0157:H7 = enterohemorrhagic E.coli,
EPEC= enteropathogenic E.coli, EIEC =enteroinvasive E. coli
50
Gastroenteritis
incubation period (Table 1)
risk assessment:
•fever
•dehydration
•toxicity
•co-morbidities
epidemiologic and clinical clues (Table 2)
Acute (< 2 weeks) (Table 3)
Persistent (> 2 weeks)
Chronic (> 4 weeks)
(Table 3)
Watery diarrhea, not
systemically ill
nausea, vomiting
≥ diarrhea
•parasitic
•small bowel overgrowth
•Whipple’s disease
•tropical sprue
•tuberculosis
•non-infectious
Viral illness or
pre-formed toxin
•S. aureus
•C. perfringens
•B. cereus
oral rehydration
Systemically ill,
inflammatory diarrhea,
elderly,
immunocompromised
No stool
cultures2
oral rehydration
•Stool O&P X 3
•Acid Fast stain of stool
•ELISA for cryptosporidium and
giardia
fecal leukocytes 1
stool culture2
C.difficile toxin3
symptoms > 714 days
if negative, consider
Upper endoscopy and biospy
Empiric therapy
Most patients with acute diarrhea do not need laboratory work-up or antibiotic therapy. Patients with
systemic toxicity or inflammatory diarrhea should be rapidly evaluated with fecal leukocytes and
cultures. Empiric therapy may be begun, though caution is suggested since some pathogens (E. coli
0157:H7) should not be treated with antibiotics.
O&P = ova and parasite, ELISA = enzyme linked immunosorbent
1
fecal leukocytes can be identified by direct stain of the stool or by demonstrating lactoferrin
2
Ova and parasites should be added if risk for exposure to Giardia, homosexual sex or international
3
stool should be sent for C. difficile toxin assay for those who are currently on or recently received
antibiotics
51
adjust therapy
or discontinue
based on results
of culture.
Therapy for Gastroenteritis
Pathogen
Bacterial
• non-typhoid
Salmonella
Antimicrobial agent
Special circumstances
• not recommended
routinely
• ciprofloxacin 500 mg po bid for 5 days
• treat 14 days if immunocompromised.
• Campylobacter •
oxycycline 500mg po
species
bid x 5 days for severe
disease.
• Shigella species • cotrimoxazole DS po bid • treat immunocompromised patient x
x 3 days
7-10 days
(if sensitive)
• ciprofloxacin 500 mg bid
x 3 days, if resistant
• Escherichia coli
¾ ETEC
• ciprofloxacin 1gm po x 1
or
• 500 mg po bid x 3 days
¾ E.coli 0157:H7 • not recommended 1
• Yersinia
• antibiotics not required
• for serious infections or bacteremia:
species
ciprofloxacin iv or po
or
• doxycycline with aminoglycoside
• Vibrio cholerae • doxycyline 300 mg po x 1
or
• ciprofloxacin 1 gm po x 1
Parasitic
• Cryptosporidium • no therapy useful
• Immunocompromised hosts, try
parvum
paromomycin 500 mg po tid x 2-4 wks
• self limited illness in
immune competent hosts
• Giardia lamblia • metronidazole 250 mg po
tid x 5-10 days
• Cyclospora
• cotrimoxazole DS bid x 3
cayentanenis
days
• Isospora belli
• cotrimoxazole 2 DS po
bid x 2-4 wks
1
increased risk of hemolytic uremic syndrome
ETEC = enterotoxigenic E.coli, E. coli 0157:H7 = enterohemorrhagic E.coli
DS= double strength
52
TREATMENT OF CLOSTRIDIUM DIFFICILE –ASSOCIATED DIARRHEA
General Principles
1. Whenever possible, the offending antibiotic should be discontinued. This alone may lead to
resolution of symptoms in up to 20% of cases.
2. Whenever possible, specific therapy should be administered orally.
3. Almost all patients respond to therapy (98%), however relapses are common (5 – 20%).
Improvement occurs within 2 – 4 days and treatment should be given for 10 days.
4. Antiperistaltic agents should be avoided since they may precipitate toxic megacolon and reduce
fecal concentrations of metronidazole.
5. Routine stool toxin assays following therapy (test-of-cure) are not recommended.
Specific Therapy
1. Metronidazole 250 mg po qid or 500 mg po TID x 10 days is the regimen of choice.
2. Vancomycin 125 mg po qid x 10 days is an alternative regimen for patients who are intolerant of,
or fail, metronidazole.
3. Relapses can be treated with metronidazole. Patients with multiple relapses may require
alternative management strategies.
53
Principles of Surgical Prophylaxis
1. National Research Council Wound Classification
Clean
- Elective, not emergent, nontraumatic, primarily closed; no acute inflammation; no break in
technique; gastrointestinal, biliary and genitourinary tracts not entered. Examples of clean
procedures include the following:
• Cardiothoracic, vascular, and neurosurgery
• Inguinal hernia repair
• Insertion of prosthetic material (joint, heart valve, gortex, pacemaker)
- Likely pathogens: S. aureus and S. epidermidis
Clean-contaminated
- Urgent or emergency case that is otherwise clean; elective opening of respiratory,
gastrointestinal, biliary or genitourinary tract with minimal spillage not encountering infected
urine or bile; minor technique break.
Examples of clean-contaminated procedures include the following:
• Colorectal surgery, biliary tree surgery, appendectomy
• Head and neck surgery, gynecologic surgery
• Burns
• Gastric surgery in patients treated with H2 blockers, antacids,
or proton pump inhibitors
• Small bowel obstruction requiring open decompression
- Likely pathogens: For head and neck procedures, streptococci and anerobes.
For colorectal and biliary tract procedures, gram-negative rods,anaerobes,
streptococci, and enterococci.
Contaminated
Nonpurulent inflammation; gross spillage from gastrointestinal tract; entry into biliary or
genitourinary tract in the presence of infected bile or urine; major break in technique.
Examples of contaminated surgeries include the following:
• Penetrating trauma < 4 hours old
• Chronic open wounds to be grafted or covered
• Perforated appendix
- Likely pathogens: Gram-negative rods, anaerobes, enterococci, staphylococci, and
streptococci
Dirty
- Purulent inflammation (eg. Abscess); preoperative perforation of respiratory, gastrointestinal,
biliary or genitourinary tract. Examples of dirty surgeries include the following:
• Perforated viscus
• Penetrating trauma > 4 hours old
- Likely pathogens: Gram-negative rods, anaerobes, enterococci, staphylococci, and
streptococci
54
Principles of Surgical Prophylaxis
Prophylactic antibiotics
A. Dose
- The prophylactic dose should be equivalent to the standard therapeutic dose.
Agent
Recommended
Dose
Cefazolin
Vancomycin
Clindamycin
Gentamicin
Metronidazole
1 gram *
15 mg/kg
900 mg
1.5 mg/kg
500 mg
* Consider 2 grams for CABG and orthopedic procedures
B. Timing
- The prophylactic parenteral dose should be completely administered within 60 minutes
or less prior to the incision.
C. Duration
- Post-operative administration of antibiotics is not advised. If used, the duration of
post-operative antibiotics should be discontinued within 24 hours after surgery end
time. If established infection is found at the time of the operation, treatment should
be continued as clinically indicated.
D. Repeated doses during the surgical procedure
REDOSE THIS DRUG IF SURGERY LASTS LONGER THAN:
Cefazolin..............................................2-4 hours
Aminoglycosides..................................2-4 hours
Clindamycin .........................................3-6 hours
E. Luminal antibiotics for colorectal procedures (to be used in addition to the
parenteral antibiotics listed under the colorectal section of the algorithm)
- One gram of oral erythromycin base and one gram of oral neomycin are given at
1 p.m., 2 p.m., and 11 p.m. the day before surgery.
55
Surgical Prophylaxis
Clean
Cefazolin or
Vancomycin *
Head & Neck **
Gastric
Dirty / Contaminated
Clean - Contaminated
OB GYN
Cefazolin or
Clindamycin +/Gentamicin *
Colorectal
Biliary
(-) cholangitis
Cefazolin +/- Metronidazole
OR
Clindamycin *
* For patients allergic to
cephalosporins or with
anaphylaxis to
penicillin
** Some authorities
would add gentamicin
for major head and
neck procedures
56
(+) cholangitis
Cefazolin + Metronidazole
OR
Gentamicin + Clindamycin *
PREVENTION OF BACTERIAL ENDOCARDITIS
American Heart Association Committee Report. Prevention of bacterial endocarditis.
JAMA 1997;277:1794-801.
1. Endocarditis prophylaxis is recommended for the following cardiac conditions:
High risk category
• Prosthetic cardiac valves, including bioprosthetic and homograft valves
• Previous bacterial endocarditis
• Complex cyanotic congenital heart disease (eg, single ventricle states,
transposition of the great arteries, tetralogy of Fallot)
• Surgically constructed systemic pulmonary shunts or conduits
Moderate risk category
• Most other congenital cardiac malformations (other than above and below)
• Acquired valvar dysfunction (eg, rheumatic heart disease)
• Hypertrophic cardiomyopathy
• Mitral valve prolapse with valvar regurgitation and/or thickened leaflets
2. Endocarditis prophylaxis is recommended for the following dental procedures if the conditions
under #1 are present: For other procedures, endocarditis prophylaxis is not indicated.
• Dental extractions
• Periodontal procedures including surgery, scaling and root planing, probing,
and recall maintenance
• Dental implant placement and reimplantation of avulsed teeth
• Endodontic (root canal) instrumentation or surgery only beyond the apex
• Subgingival placement of antibiotic fibers or strips
• Initial placement of orthodontic bands but not brackets
• Intraligamentary local anesthetic injections
• Prophylactic cleaning of teeth or implants where bleeding is anticipated
3. Other procedures where endocarditis prophylaxis is recommended if the conditions under #1 are
present. For other gastrointestinal, genitourinary, and respiratory procedures, prophylaxis is not
indicated.
Respiratory tract
• Tonsillectomy and/or adenoidectomy
• Surgical operations that involve respiratory mucosa
• Bronchoscopy with a rigid bronchoscope
Gastrointestinal tract
• Sclerotherapy for esophageal varices
• Esophageal stricture dilation
• Endoscopic retrograde cholangiography with biliary obstruction
• Biliary tract surgery
• Surgical operations that involve intestinal mucosa
Genitourinary tract
• Prostatic surgery
• Cystoscopy
• Urethral dilation
57
PREVENTION OF BACTERIAL ENDOCARDITIS
Table 1. Recommended prophylactic regimens for dental, oral, respiratory tract, or
esophageal procedure
Situation
Agent
Regimen
Standard general prophylaxis Amoxicillin
2g PO 1 hr before the procedure
Unable to take oral
2g IV/IM within 30 min before the
Ampicillin
medications
Allergic to penicillin
procedure
Clindamycin
600mg PO 1 hr before the procedure
or
Cephalexin
2g PO 1 hr before the procedure
or
Azithromycin
500mg PO 1 hr before the procedure
Allergic to penicillin and
Clindamycin
600mg IV within 30 min before the
unable to take oral
or
procedure
medications
Cefazolin
1g IV/IM within 30 min before the
procedure
Table 2. Recommended regimens for genitourinary gastrointestinal (excluding esophageal)
procedures
Situation
High-risk Patients
Agents
Regimen
Ampicillin plus
Ampicillin 2g IV/IM plus gentamicin IV/IM
gentamicin
1.5mg/kg (not to exceed 120 mg) within 30
min of starting the procedure; 6 hr later,
ampicillin 1g IM/IV or amoxicillin 1g PO
High-risk patients allergic to
Vancomycin plus
Vancomycin 1g IV plus gentamicin IV/IM
ampicillin/amoxicillin
gentamicin
1.5mg/kg (not to exceed 120 mg).
Complete infusions within 30 min of starting
the procedure.
Moderate-risk patients
Amoxicillin or
Amoxicillin 2g PO 1 hr before the procedure,
ampicillin
or ampicillin 2g IV/IM within 30 min of
starting the procedure
Moderate-risk patients allergic
to ampicllin/amoxicillin
Vancomycin
Vancomycin 1g; complete infusion within 30
min of starting the procedure.
58
ENDOCARDITIS PROPHYLAXIS
Is patient at Risk ?
No Prophylaxis
NO
(see #1)
YES
(High vs Moderate Risk)
Type of Procedure
Genitourinary / Gastrointestinal
procedure requiring prophylaxis
Dental, Oral, Respiratory,
(See # 3)
or esophageal procedure
(See #2 and #3)
NO
No
Prophylaxis*
YES
NO
YES
Moderate
No
Prophylaxis*
High Risk
Select Antibiotics
Risk
(Table 1)
Select Antibiotics
Select Antibiotics
(Table 2)
(Table 2)
*Prophylaxis is optional for high risk patients undergoing:
Flexible bronchoscopy, transesophageal echocardiography,
endoscopy with or without gastrointestinal biopsy,
vaginal hysterectomy, and vaginal delivery
59
THERAPY FOR SELECTED SEXUALLY TRANSMITTED DISEASES
Reference: 2002 Sexually Transmitted Diseases Treatment Guidelines
MMWR Vol. 51, No. RR-06, May 10, 2002
1. Genital Herpes Simplex Virus
A) First Clinical Episode
• Acyclovir 400 mg PO TID or 200 mg 5x/d for 7-10 days.
• Famciclovir 250 mg PO TID for 7-10 days
• Valacyclovir 1 gram PO BID for 7-10 days
B) Recurrent Episodes
- Episodic Treatment
• Acyclovir 400 mg PO TID or 200 mg 5x/d for 5 days
• Acyclovir 800 mg PO BID x 5 days
• Famciclovir 125 mg PO BID for 5 days
• Valacyclovir 500 mg PO BID for 3-5 days
• Valacyclovir 1 gram PO QD x 5 days
- Suppressive Therapy
• Acyclovir 400 mg PO BID
• Famciclovir 250 mg PO BID
• Valacyclovir 500 mg QD or 1000 mg QD
2. Syphilis *
A) Primary, secondary and early latent
• Benzathine penicillin G 2.4 million units IM as a single dose
• Doxycycline 100 mg PO BID for 14 days
• Tetracycline 500 mg PO QID for 14 days
• Ceftriaxone 1 gram IM for 8-10 days (limited data to support this regimen)
• Erythromycin 500 mg PO QID for 14 days
B) Late latent, unknown duration, tertiary
• Benzathine penicillin G 2.4 million units IM weekly x 3
• Tetracycline 500 mg PO QID for 28 days
C) Neurosyphilis
• Penicillin G 3-4 million units IV q4h for 10-14 days
• Procaine penicillin 2.4 million units IM QD plus probenecid 500 mg QID for 10-14
days +/- benzathine penicillin 2.4 million units IM at the end of therapy
* Penicillin is the preferred drug for treatment of all stages of syphilis. Data to support the use of
alternatives to penicillin (in the presence of penicillin allergy) is limited.
60
THERAPY FOR SELECTED SEXUALLY TRANSMITTED DISEASES
3. Urethritis and Cervicits
A) Non-gonococcal urethritis, mucopurulent cervicitis
• Azithromycin 1 gram PO x 1 dose
• Erythromycin 500 mg PO QID for 7 days
• Ofloxacin 300 mg PO BID for 7 days
B) Gonococcal Infection
- Uncomplicated
• Cefixime 400 mg PO x 1 dose
• Ceftriaxone 125 mg IM x 1 dose
• Ciprofloxacin 500 mg PO x 1 dose
• Ofloxacin 400 mg x 1 dose
• Plus: Azithromycin 1 gram x 1 dose
or Doxycycline 100 mg PO BID for 7 days
Disseminated
• Ceftriaxone 1 gram IV/IM q24. Once clinically improved, switch to oral
cefpodoxime 200 mg q12 to complete a 7 day course.
• Ciprofloxacin 400 mg IV q12. Once clinically improved, switch to oral
ciprofloxacin 500 mg q12 to complete a 7 day course.
61
Management of Exposures to Bloodborne Pathogens in Healthcare
1. Promptly report an exposure to the FAHC Employee Health office. Please telephone Employee
Health (7-1300) and FAX the “Employee Report of Event” form (7-5105). Do not wait to call, or
report exposures by snail mail. After 4 p.m. and on weekends and holidays, promptly seek care in
the Emergency Department, leave a telephone message and FAX with Employee Health, and
follow-up with Employee Health the next business day.
2. “Bloodborne pathogens” include HIV, hepatitis B and hepatitis C.
3. An “exposure” is defined as a percutaneous injury or contact of mucosa or nonintact skin with
blood, tissue, or potentially contagious body fluids (blood, fluid with visible blood, semen, vaginal
secretions, CSF, synovial, pleural, peritoneal, pericardial and amniotic). Fluids not usually
considered infectious include feces, nasal, saliva, sputum, sweat, tears, urine, and vomit – unless
they are bloody. For human bites, both the biter and the bitten are considered exposed.
4. Estimated risk of infection following percutaneous exposure:
a. Hepatitis B: may exceed 30% (depends on e antigen status of host and assumes
b. healthcare worker not immune from vaccination or prior infection).
c. Hepatitis C: approximately 2%.
d. HIV: approximately 0.3%.
5. Prompt first aid, reporting, evaluation, counseling, treatment, and follow-up are all important
following an exposure.
6. Prevention is always the best strategy. All healthcare workers who may have contact with blood,
body fluids, or sharps should be vaccinated against hepatitis B and have serologic evidence of
response to the vaccine. Handwashing, the proper use and disposal of sharps, and the
appropriate use of personal protective equipment are the best ways to reduce exposures. Never
recap needles! The user of a sharp is responsible for it’s disposal.
7. Wounds and skin that have been exposed should be washed with soap and water. Mucous
membranes should be flushed with water.
8. The Employee Health office will coordinate obtaining consent and testing the source patient for all
3 pathogens as soon as possible. Please do not order source patient testing yourself. A
rapid HIV test will be performed whenever possible.
9. Post-exposure treatment will be coordinated by Employee Health, the Emergency Department, the
Infectious Diseases Unit, and Pharmacy.
10. Records of employee exposures, testing, and management are confidentially maintained in the
Employee Health office and do not become part of the employee’s medical record.
Confidentiality must be maintained for healthcare workers and source patients.
11. Exposures to HIV, and decisions about antiretroviral therapy, should be discussed with the
Infectious Diseases attending on call.
12. Summary of key points:
a. Practice prevention – hepatitis B vaccination, handwashing, proper use of sharps, proper
use of protective equipment (gloves, gowns, eye protection)
b. Understand what constitutes an exposure
c. Prompt reporting of exposures
d. Let Employee Health consent and test source patients and employees
e. Maintain confidentiality.
62
ORAL ANTIMICROBIAL THERAPY
Introduction .............................................62
Selected agents ......................................63-66
-Amoxicillin / clavulanate.................64
-Azithromycin ..................................64
-Cefpodoxime..................................65
-Ciprofloxacin ..................................65
-Levofloxacin...................................66
-TMP/SMX ......................................66
Intravenous to oral switch table ..............67
Costs to patients .....................................68-69
63
ORAL ANTIMICROBIAL THERAPY
1. The historical preference for the intravenous administration of antibiotics has been
reevaluated in light of the availability of oral agents with reliable oral absorption. These
antimicrobials produce adequate blood levels following oral administration. In addition, the
oral route of administration avoids intravenous therapy which is associated with potentially
serious complications. The literature is replete with evidence that an early switch or the
initial use of oral antibiotics can result in a decreased risk of line infection, decreased
hospitalization, and decreased length of stay if admission is required. Such outcomes as
these will undoubtedly benefit the entire health care system.
2. The following agents have reliable absorption (good bioavailability). Therefore, these
medications should be given orally whenever a patient can take oral medication and has a
functional GI tract.
•
•
•
•
•
•
•
•
•
Ciprofloxacin*
Levofloxacin*
Trovafloxacin*
Azithromycin*
Clindamycin
Metronidazole
TMP/SMX*
Doxycycline
Fluconazole
----------------• Amoxicillin /
clavulanate*
• Cefpodoxime*
Oral formulation only
3. Consideration should be given to an early switch to one of the above agents if the following
clinical conditions are present:
- The patient has a functional gastrointestinal tract and is able to take oral medication
- The patient is clinically stable or improving (decreasing temperature, WBC, etc.)
- There is an equivalent or appropriate oral agent available (see the above list of oral
antibiotics)
* These agents are reviewed alphabetically in the next section. Information that is provided
includes:
Antibiotic class
Spectrum of activity
Clinical uses
Dosage adjustment in renal dysfunction
Warnings
64
Selected Oral Agents
Amoxicillin / Clavulanate
Class
Beta-lactam / beta-lactamase inhibitor combination
Spectrum of Activity
Beta-lactamase producing staphylococci and enterococci
Streptococci including Streptococcus pneumoniae
H. influenzae and M. catarrhalis
Some aerobic gram-negatives including E. coli, Klebsiella, and Proteus species
Anaerobic gram-negatives including B. fragilis
Pasteurella species
Possible Uses
Animal bite wounds
Mixed infections involving aerobes and anaerobes such as diverticulitis and
diabetic foot infections
Usual Dose
500 mg TID or 875 mg BID
Dose adjustment required in renal insufficiency ?
YES
Warnings / Side Effects
Previous hypersensitivity to any penicillin /-GI upset especially diarrhea
Azithromycin
Class
Macrolide (Azalide)
Staphylococci* and streptococci* including Streptococcus pneumoniae
Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila
No activity against enteric gram-negatives and anaerobes
GI upset
* Not a drug of choice for staphylococci and streptococci
Possible Uses
Community acquired pneumonia and uncomplicated soft-tissue infections
Exacerbation of COPD
Otitis Media
Single dose therapy for nongonococcal urethritis (chlamydia). The dose is
1 gram.
Usual Dose
500 mg on day 1 followed by 250 mg q24 on days 2-5
NO
Previous hypersensitivity to azithromycin, erythromycin , or any other macrolide
antibiotic
65
Cefpodoxime
Class
Third generation cephalosporin
Staphylococci and streptococci including Streptococcus pneumoniae
Other aerobic gram-negatives including E. coli, Klebsiella, and Proteus mirabilis
No activity against anaerobes, P.aeruginosa. Enterobacter, Serratia, or
Enterococcus species
Possible Uses
Community acquired pneumonia, urinary tract infections, and uncomplicated soft
tissue infections
Exacerbation of COPD
Otitis Media
Single dose (200 mg) for gonococcal urethritis
Completion of antimicrobial therapy in patient who have been stabilized on
ceftriaxone
Usual Dose
200 mg BID for community acquired pneumonia
YES
Previous hypersensitivity to cefpodoxime, cephalosporins, or penicillins
GI upset
Ciprofloxacin
Class
Quinolone
Aerobic gram-negatives including P. aeruginosa
Poor activity against streptococci and anaerobes
Staphylococci and methicillin resistant Staphylococcus aureus (MRSA) are
frequently resistant
Possible Uses
Gram negative infections resistant to TMP/SMZ and cephalosporins
Gram negative infections of the bone and joint
Travelers' diarrhea
Usual Dose
500 to 750 mg BID
YES
Previous hypersensitivity to ciprofloxacin or other quinolones
Not recommended in children < 18 years of age
Not recommended in pregnant women or nursing mothers
GI upset
66
Levofloxacin
Class
Quinolone
Staphylococci and streptococci including Streptococcus pneumoniae
Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila
Aerobic gram-negatives including P. aeruginosa.
Possible Uses
Community acquired pneumonia
Nosocomial pneumonia
Usual Dose
500 mg q24 for community acquired pneumonia
750 mg q24 for nosocomial pneumonia
YES
Previous hypersensitivity to ciprofloxacin or other quinolones
Not recommended in children < 18 years of age
Not recommended in pregnant women or nursing mothers
Trimethoprim-Sulfamethoxazole (TMP / SMX or Co-trimoxazole)
Class
Folate antagonist
Limited activity against staphylococci, streptococci including Streptococcus
pneumoniae, and H. influenzae -M. catarrhalis
Some aerobic gram-negatives including E. coli, Klebsiella, Proteus, Enterobacter,
and Serratia species
Pneumocystis carinii, Listeria and Legionella species
Possible Uses
Non-ICU nosocomial pneumonia
Urinary tract infections
Usual Dose
One double strength (DS) tablet BID
YES
Previous hypersensitivity to sulfonamides or trimethoprim
Contraindicated in pregnant and lactating women
Rash and GI upset
Bone marrow suppression with high doses
67
INTRAVENOUS TO ORAL SWITCH TABLE
Intravenous Antimicrobial
Oral Equivalent 1
Oral Dose
Ampicillin
Amoxicillin
500mg q8h
Ampicillin / Sulbactam
875mg BID
Cefazolin
Cephalexin
500mg q6h
Cefotetan
or
Cefpodoxime+ Metrondiazole
875mg BID
or
200mg BID+ 500mg
TID
Ceftazidime
Ciprofloxacin
500 mg BID 2
Ceftriaxone
Cefopodoxime
200mg BID
Ciprofloxacin
Ciprofloxacin
500mg BID 2
Clindamycin
Clindamycin
300mg QID
Levofloxacin
Levofloxacin
500mg q24h 3
1
Antibiotic therapy should be based on sensitivity data if available.
2
For P. aeruginosa, 750mg BID is recommended.
3
For nosocomial pneumonia, 750mg q24h is recommended
68
ANTIMICROBIAL COSTS
ORAL ANTIMICROBIAL AGENTS: TYPICAL RETAIL COST TO PATIENTS
FOR 10-DAY PRESCRIPTION
Antibiotic
Dose
(mg)
Doses/
Day
Cost($)/
10 Days
Antibiotic
Beta-Lactams
Dose
(mg)
Doses/
Day
Cost($)/
10 Days
200
2
96.00
Beta-Lactams
Penicillin VK
250
500
4
4
6.30
9.20
Amoxicillin
250
500
3
3
8.00
11.00
Amoxicillin/clavulanate
(Augmentin)
250
500
3
3
69.50
113.00
Dicloxacillin
250
500
4
4
25.00
43.00
Erythromycin base
250
500
4
4
8.50
14.00
Cephalexin (Keflex)
250
500
4
4
21.00
30.00
Erythromycin base
333
3
10.00
Cefadroxil (Duricef)
500
1000
1
1
44.00
86.00
Erythromycin
ethylsuccinate (EES)
400
4
17.00
Cefaclor (Ceclor)
250
500
3
3
44.00
108.00
Clarithromycin
(Biaxin)
250
500
2
2
81.00
81.00
Cefuroxime (Ceftin)
250
500
2
2
89.00
163.00
Azithromycin **
(Zithromax)
250
1
Loracarbef (Lorabid)
200
200(2)
2
2
87.00
170.00
** 1st Dose is 500mg
250
500
2
2
74.00
142.00
Cefprozil (Cefzil)
Cefpodoxime (Vantin)
Macrolides
69
51.00/6
(5 days)
Antibiotic
Dose
(mg)
Doses/
Day
Cost($)/
10 Days
Antibiotic
Sulfonamides and Trimethoprim
Dose
(mg)
Doses/
Day
Cost($)/
10 Days
Urinary Tract Infections Only
SS
DS
2
2
8.00
8.50
Nitrofurantoin
(Macrodantin)
(Macrobid)
50
100
100
4
4
2
30.00
60.00
35.00
Sulfadiazine
(Microsulfon)
500
500(2)
4
4
25.00
50.00
Methenamine
(Mandelamine)
1000
4
35.00
Sulfisoxazole
(Gantrisin)
500
500(2)
4
4
10.00
17.00
Miscellaneous
Trimethoprim
100
2
9.10
Tetracycine
250
500
4
4
5.50
6.40
Doxycycline
(Vibramycin)
100
100
1
2
8.00
12.00
Co-Trimoxazole
(Bactrim,Septra)
Fluoroquinolones
Norfloxacin (Noroxin)
400
2
69.00
Minocycline
100
2
27.00
Ciprofloxacin
(Cipro)
250
500
750
2
2
2
84.00
90.00
124.00
Clindamycin
(Cleocin)
150
150(2)
4
4
24.00
4000.00
Ofloxacin (Floxin)
200
300
400
2
2
2
82.00
97.00
102.00
Metronidazole
(Flagyl)
250
4
13.00
Lomefloxacin
(Maxaquin)
400
1
91.00
Vancomycin
(Vancocin)
125
250
4
4
269.00
501.00
Enoxacin (Penetrex)
400
2
75.00
70
ANTIBIOTIC PRESCRIBING
Antibiotic dosing in renal insufficiency.................. 71
Antimicrobial drug interactions ............................. 72-73
Antimicrobials in pregnancy ................................. 74-75
71
RECOMMENDED ANTIMICROBIAL DOSAGE IN RENAL IMPAIRMENT
Antimicrobial Agent
Acyclovir
Dosing Range
5-10 mg/kg q8
Acyclovir PO
Amphotericin B
30-50
100% q12
Doses for Renal Failure: Crcl (ml/min)
10-30
100% q24
< 10
50% q24
200-800 mg 5x/day
100%
100% q8
100% q12
0.5-1 mg/kg q24
100%
100%
100%
Amoxicillin
250-500 mg q8
100 % q8
100 % q12
100 % q24
Amoxicillin / clavulanate
250-500 mg q8
100 % q8
100 % q12
100 % q24
Ampicillin
1-2 gm q4-6
100% q8
100% q8-12
100% q12-16
1.5 to 3 gm q6h
100% q6-8
100% q12
100% q24h
Azithromycin PO
500 mg on day 1 then
250 mg on days 2-5
100 %
100 %
100 %
Azithromycin IV
500 mg q24
100 %
100 %
100 %
Aztreonam
1-2 gm q8
100%
100% q12
100% q24
Cefazolin
1-2 gm q8
100% q12
50% q12
50% q24
Cefotetan
1-2 gm q12
100%
100% q24
100% q48
Cefpodoxime proxetil
200 mg q12
100%
100% q24
100% q24
Ceftazidime
1-2 gm q8
100% q12
100% q24
50% q24
Ceftriaxone a
1 gm q24 (see footnote)
100%
100%
100%
750 mg q8
100%
100% q12
100% q24
Cefuroxime
Cephalexin PO
250-500 mg q6
100%
100% q8-12
50% q12
Ciprofloxacin IV
200-400 mg q12
100%
100% q18
100% q24
Ciprofloxacin PO
500-750 mg q12
500 mg q12
500 mg q18
500 mg q24
Clindamycin
600-900 mg q8
100%
100%
100%
Clindamycin PO
150-450 mg q6
100%
100%
100%
Co-trimoxazole IV
(80mg TMP/5ml)
10-20 ml q12
(10 ml = 1 double strength
tablet)
100%
50% q12
50 % q24 b
Co-trimoxazole PO
1 double strength q12
100%
1 single strength q12
1 single strength q24 b
Doxycycline IV/PO c
100mg q12-24
100%
100%
100%
Fluconazole IV/PO c
200-400 mg q24
50% q24
50% q24
50% q48
Ganciclovir (induct)
5mg/kg q12
50% q24
25% q24
500 mg q24
Crcl 20-49 use 500 mg x1 then 250 mg q24h; Crcl 1019 use 500mg x1 then 250mg q48h.
500 mg x1 then 250 mg
q48
Crcl 20-49 use 750 mg q48; Crcl 10-19 use 750 mg
x1 then 500 mg q48
750 mg x1 then 500 mg
q48
Levofloxacin IV/PO
c
Levofloxacin IV/PO c
750 mg q24 d
Meropenem
Metronidazole IV/PO
1 gm q8
c
100 % q12
50 % q12
50 % q24
100% q8-12
500 mg q8
100%
100%
1-2 gm q4-6
100%
100%
100%
Penicillin G
1-2 million units q4-6 e
100% q6
100% q6-8
100% q8-12
Piperacillin
3-4 gm q6
100% q8
100% q8-12
100% q12
Nafcillin
3.375 gm q6
Crcl > 40 use 3.375 gm q6; Crcl 20-40 use 2.25 gm q6;
Crcl < 20 use 2.25 gm q8
4.5 gm q6h f
Crcl > 40 use 4.5 gm q6; Crcl 20-40 use 3.375 gm q6;
Crcl < 20 use 2.25 gm q6
a
For CNS infections, the dose of ceftriaxone is 2 grams q12h.
Not recommended for creatinine clearance of less than 15 ml/min
c
Intravenous and oral dosing regimens are identical
d
Recommended dose for nosocomial pneumonia
e
For CNS infections, the dose of penicillin G is 4 million units q4h
f
Recommended dose for nosocomial pneumonia
b
72
IMPORTANT DRUG INTERACTIONS WITH ANTIBIOTICS
Antibiotic
Interacting Drug
Effect
Management
Phenytoin
Warfarin
Increased plasma levels of
interacting drug due to
decreased clearance
Avoid interaction or monitor closely
for toxicity
Oral Sulfonylureas
Chlorpropamide
Glipizide
Glyburide, etc
Increased hypoglycemic
effect due to decreased
protein binding of interacting
drug
Avoid interaction or monitor for
hypoglycemia
Antacids
Decreased absorption of
doxycycline
Separate by at least 2 hrs
Warfarin
Potentiation of anti-coagulant
effect
Avoid or monitor INR closely
Fluconazole
Itraconazole
Voriconazole
Cyclosporine
Oral Sulfonylureas
Phenytoin
Warfarin
inhibition of Cytochrome P450
oxidase system
Avoid interaction or decrease dose of
interacting drug by 25 to 50%.
Monitor closely.
Fluoroquinolones
Ciprofloxacin
Levofloxacin
Norfloxacin
Levofloxacin
Al , Ca , Mg
products
(antacids, etc)
++
Multivites w/ Zn
Significant decrease in
absorption of antibiotic
Avoid or give interacting drug at least
6 hrs before or 2 hrs after FQ
Sucralfate
Significant decrease in
absorption of antibiotic
Avoid entirely
Theophylline
Caffeine
Increase in plasma levels of
theophylline and caffeine
Decrease dose of
interacting drug by 50% and monitor
Benzodiazepines
Midazolam
Triazolam
Carbamazepine
Cyclosporine
Theophylline
Warfarin
inhibition of CYP3A enzymes
of Cytochrome P450 oxidase
system
Avoid interaction or decrease dose of
interacting drug by 25 to 50%.
Co-trimoxazole
Doxycycline
Ciprofloxacin
Enoxacin
Norfloxacin
Macrolides
Erythromycin
Clarithromycin
++
++
++
73
Monitor closely.
Antibiotic
Macrolides
Erythromycin
Clarithromycin
Metronidazole
Rifampin
Rifabutin
Interacting Drug
Effect
Management
Cisapride
Nonsedating antihistamines:
Astemizole
Loratidine
Terfenadine
inhibition of CYP3A enzymes
of Cytochrome P450 oxidase
system
Absolute contraindication due to life threatening
arrhythmias
Digoxin
Increased digoxin levels
due to decreased gut
metabolism in 10% of
population
Monitor for digoxin toxicity
Alcohol
Inhibits alcohol
dehydrogenase causing
disulfiram-like effect
Avoid alcoholcontaining products
Warfarin
Potentiation of anti-coagulant
effect
Avoid or monitor INR closely
Beta-blockers
Corticisteroids
Cyclosporine
Digoxin
Estrogen
Fluconazole
Opioid analgesics
Quinidine
Sulfonylureas
Verapamil
Decreased plasma levels of
interacting drugs due to
induction of multiple enzymes
of
Cytochrome P450 oxidase
system
Avoid or monitor closely for
decreased clinical efficacy of
interacting drug
74
ANTIMICROBIAL USE IN PREGNANCY
Pregnancy Risk Category
X
D
C
B
A
Description *
Studies in animals or human beings have demonstrated
fetal abnormalities or there is evidence of fetal risk based
on human experience or both, and the risk of the use of
the drug in pregnant women clearly outweighs any
possible benefit. The drug is contraindicated in women
who are or may become pregnant.
There is positive evidence of human fetal risk, but the
benefits from use in pregnant women may be acceptable
despite the risk (e.g., if the drug is needed in a lifethreatening situation or for a serious disease for which
safer drugs cannot be used or are ineffective).
Either studies in animals have revealed adverse effects on
the fetus (teratogenic or embryocidal or other) and there
are no controlled studies in women or studies in women
and animals are not available. Drugs should be given only
if the potential benefit justifies the potential risk to the
fetus.
Either animal-reproduction studies have not demonstrated
a fetal risk but there are no controlled studies in pregnant
women or animal reproduction studies have shown an
adverse effect (other than a decrease in fertility) that was
not confirmed in controlled studies in women in the first
trimester (and there is no evidence of a risk in later
trimesters).
Controlled studies in women fail to demonstrate a risk to
the fetus in the first trimester (and there is no evidence of
a risk in later trimesters), and the possibility of fetal harm
appears remote.
* The descriptions for the risk categories are those used by the Food and Drug Administration.
Federal Register 1980;44:37434-67.
75
ANTIMICROBIAL USE IN PREGNANCY
Consultation with Obstetrics or Infectious Disease may be considered
Antimicrobials generally considered to be safe in pregnancy
Risk Category
Amphotericin B .................................................................... B
Azithromycin ........................................................................ B
Aztreonam ........................................................................... B
Cephalosporins.................................................................... B
Clindamycin ......................................................................... B
Erythromycin........................................................................ B
Famciclovir........................................................................... B
Metronidazole ...................................................................... B
Nitrofurantoin 1 ..................................................................... B
Penicillins............................................................................. B
Valacyclovir.......................................................................... B
Antimicrobials to be used with caution in pregnancy
Acyclovir .............................................................................. C
Aminoglycosides.................................................................. D
Clarithromycin...................................................................... C
Ganciclovir ........................................................................... C
Fluconazole ......................................................................... C
Imipenem-cilastatin.............................................................. C
Indinavir ............................................................................... C
Ketoconazole ....................................................................... C
Lamivudine .......................................................................... C
Nelfinavir.............................................................................. B
Nevirapine............................................................................ C
Nystatin................................................................................ C
Rifampin............................................................................... C
Ritonavir............................................................................... B
Sulfonamides 1,2 ................................................................... B
Stavudine............................................................................. C
Sulfamethoxazole / trimethroprim 1,2 .................................... B
Trimethoprim........................................................................ C
Zalcitabine ........................................................................... C
Vancomycin ......................................................................... C
Zidovudine ........................................................................... C
Antimicrobials which should be avoided in pregnancy
Efavirenz.............................................................................. C
Quinolones .......................................................................... C
Ribavirin............................................................................... X
Tetracyclines ....................................................................... D
1
Do not administer to pregnant patients with G-6-PD deficiency because of the risk of hemolysis to
the mother and fetus
2
Risk factor D if administered near term
76