All Microbiology Is Local

“ALL MICROBIOLOGY IS LOCAL.”

Paraphrase of a famous quotation by Thomas P. (Tip) O’Neill,

United States representative from Massachusetts from 1953 to 1987

and Speaker of the House of Representatives from 1977 to 1987

ANTIBIOTIC ALGORITHMS FOR ADULT PATIENTS

AND ANTIBIOGRAMS AT MONTEFIORE AND EINSTEIN

6th edition

TABLE OF CONTENTS

Click on a subject to go to its page.

Why use this booklet?...... 2

Why not just use broad-spectrum antibiotics?...... 3

List of restricted antibiotics...... 4

Non-formulary antibiotics...... 5

Automatic antibioticsubstitutions...... 5

General principles of treating infectious diseases....6

Prior to selecting antibiotics...... 7-9

C.M.S. standardsfor pneumonia...... 10

Predictionofmortality in community-acquired pneumonia (the “Fine score”)11-12

Algorithms for empiric antibiotics in adults

Community-acquired pneumonia...... 13-14

Nosocomial pneumonia...... 15-16

Skin and soft tissue infections...... 17-18

Bacterial meningitis...... 19-20

Intra-abdominal infections...... 21-22

Sepsiswithout an obvious source...... 23-24

Antibiotic prophylaxis in adults with cancer.25-27

Febrile neutropenia in cancer patients...... 28-29

Estimation (calculation) of creatinine clearance....30

Vancomycin dosing guidelines...... 30

Aminoglycoside dosing guidelines...... 31

Using serum antibiotic levels...... 32

Antibiotics for perioperative prophylaxis

Principles...... 33

“Clean” surgery...... 34

“Clean-contaminated” surgery...... 35

Antibiograms

Bacterial susceptibility and resistance data

at Montefiore...... 36-40

at Einstein...... 41-43

Fungal susceptibility and resistance data...... 44

Important information aboutthe antibiograms45

Microbiology Laboratory FAQs...... 46-50

Quinolone guide – ciprofloxacin vs. moxifloxacin..51

References...... 52-56

Documentation of sepsis...... 57

Afterthought...... 58

WHY USE THIS BOOKLET WHEN THERE ALREADY SEEM TO BE

NATIONAL GUIDELINES FOR EVERYTHING?

Formulas, critical pathways, algorithms, and recommendations published by national groups for the empiric treatment of various types of infectious diseases are helpful starting points in the selection of antibiotic therapy. However, by their nature, they cannot apply to every situation. Broad-based formulas often must be modified to account for a number of factors — most importantly the antibiotic susceptibility patterns of common local bacteria and the frequency with which those organisms are encountered. Many published consensus guidelines for empiric antibiotic therapy contain statements that remind physicians to be familiar with their local data and adjust their patients’ treatments accordingly, but this critically important detail is often in the background and overlooked. The guidelines in this booklet are local — based on the most recent antibiograms fromthe Montefiore Microbiology Laboratory and the antibiotics available in the Montefiore/Einstein Pharmacy. They were developed by the Department of Pharmacy and the Division of Infectious Diseases of the Department of Medicine, and took into consideration recommendations by national professional societies.

No set of formulas, no matter how comprehensive or how carefully constructed, apply to every patient or replace sound clinical decision making. It should also be noted that some antibiotic recommendations contained in this booklet are different from the indications in their package inserts. Finally, physicians should obtain consultations from appropriate subspecialists whenever patients’ diagnoses are unclear, unusually complex cases are encountered, hazardous treatment is planned, unexpected complications occur, or the response to treatment seems unusually delayed.

WHY NOT JUST USE BROAD-SPECTRUM ANTIBIOTICS ALL THE TIME?

Although it’s reasonable to start very broad-spectrum antibiotics for infected patients who are very ill (i.e., when all possible organisms have to be “covered”), there are many reasons to not use the broadest possible coverage all the time. First, there’s the resistance issue. Bacteria eventually become resistant to whatever is used, and once they do, they often stay that way, turning broad-spectrum antibiotics into narrow spectrum antibiotics, and making many older antibiotics much less useful than previously. (Eventually can be a short time or a long time, and like the rest of the future, it can’t be predicted well).

There’s also the money issue – it’s much easier for a pharmaceutical company to make a profit on a medication used to treat diabetes or high cholesterol because a person might be taking it for years, or for cancer because the price of a single course of chemotherapy is thousands of dollars. Whatever you think of pharmaceutical companies (i.e., whether they make money to return it to their officers, stockholders, and investors, or use it to finance education and research), they must make a profit to be successful.

For more than a decade, very few pharmaceutical companies have been developing antibiotics, and therefore, few are still sold only by their brand name. Some well-known older brands (e.g., Kefzol) are no longer even available because they are made generically (generic cefazolin is still made). Some older antibiotics (e.g., Timentin) are sold only under their brand name because even though their patents have expired, they are relatively low-profit and not manufactured by generic drug makers. (A manufacturer cannot stop production of a medication without giving six months notice to the F.D.A. and either stating that it is no longer needed or that an alternative source exists, so the original brand manufacturer can be forced to continue to make it.)

When old antibiotics lose their antimicrobial activity and new antibiotics don’t make as much money as other categories of medications, that’s a big problem. That is the current situation, and why we have to preserve the antibiotics we have even more so than previously.

Other reasons to use antibiotics smartly, and not rely on broad-spectrum antibiotics in every single patient, include unanticipated problems like broad-spectrum quinolones being linked to the development of a substantially higher incidence of Clostridium difficile colitis. Some C. difficile seen nowadays is not only resistant to quinolones, but often causes more severe colitis. Remember, the bacteria always win. There are many other reasons to use antibiotics wisely, but there’s not enough space in this booklet to review all of them.

RESTRICTED ANTIBIOTICS

Except as noted, the following require approval by a member of the Division of Infectious Diseases for inpatient use.

Callers for restricted antibiotics should know the reason for the request and the patient’s medical record number, age and weight. For approval of more than one dose, the patient’s age renal function must also be known.

acyclovir...... intravenous

also approvable by Dermatology;

no approval is needed for capsules

albendazole...... tablets

amikacin...... intramuscular and intravenous

amphotericin B deoxycholate...... intravenous

no approval is needed for bladder irrigation

amphotericin B lipid complex and liposomal ...... intravenous

azithromycin...... intravenous and tablets

no approval is needed for use on Pediatrics,

1200 mg weekly doses for MAI prophylaxis,

and one-time 1000 mg doses for Chlamydia trachomatis

aztreonam...... intravenous

cefepime...... intravenous

no approval is needed for use in I.C.U.s and Oncology

cefotaxime...... intramuscular and intravenous

only for use on Pediatrics (for adults, use ceftriaxone)

ceftriaxone...intramuscular and intravenous more than 1000 mg/d

no approval is needed for 1000 mg/d and less

chloramphenicol...... intravenous

no approval is needed for tablets

cidofovir...... intravenous

ciprofloxacin...... intravenous

no approval is needed for tablets

clarithromycin...... tablets

no approval is needed to treat M. avium-intracellulare or H. pylori

daptomycin...... intravenous

fluconazole...... tablets, oral suspension, and intravenous

no approval is needed for 400 mg/d or less in AIDS patients

flucytosine...... capsules

foscarnet...... intravenous

ganciclovir...... intravenous

oral is non-formulary

(use oral valganciclovir, which also needs approval)

imipenem...... intramuscular and intravenous

itraconazole...... capsules and oral solution

also approvable by Dermatology; intravenous is non-formulary

linezolid...... tablets and intravenous

meropenem...... intravenous

should be used only on Pediatrics and for “imipenem-R meropenem-S” organisms in adults (otherwise, even for patients with seizures, use imipenem, which also needs approval)

micafungin...... intravenous

moxifloxacin...... intravenous

no approval is needed for tablets

pentamidine...... intramuscular, intravenous, and inhaled

piperacillin-tazobactam...... intravenous

restricted only in the E.R. and on Vascular Surgery

polymyxin B...... intravenous

rifabutin...... tablets

tigecycline...... intravenous

valganciclovir...... capsules

also approvable by Renal and by Transplant Surgery

vancomycin...... capsules, oral solution, and intravenous

approval is needed for more than 72 hours of intravenous administration, and requires a documented infection;

approval is needed at all times for oral administration

voriconazole...... tablets, oral suspension, and intravenous

NON-FORMULARY ANTIBIOTICS

Non-formulary antibiotics are not routinely available because there is nearly always another antibiotic already on the formulary with an equal or better efficacy and toxicity profile. For example, piperacillin-tazobactam can be used instead of ticarcillin-clavulanic acid, cefepime instead of ceftazidime, and a variety of cephalosporins instead of cefuroxime. For the rare instances that non-formulary items are necessary (e.g., infections caused by bacteria that are resistant to all antibiotics on the formulary), consultations by Infectious Diseases should be obtained. If they agree that the non-formulary item is necessary, it will be obtained by the Pharmacy on an expedited basis.

ANTIBIOTIC SUBSTITUTIONS

Unless a member of the Division of Infectious Diseases makes an exception, the Pharmacy automatically makes these substitutions:

As “therapeutically equivalent alternatives”

liposomal amphotericin B is changed to...amphotericin B lipid complex

caspofungin is changed to...... micafungin

cefotaxime is changed to...... ceftriaxone (except on Pediatrics)

cefoxitin is changed to...... cefotetan (except on Pediatrics)

intravenous cefuroxime is changed to..ceftriaxone (except on Pediatrics)

oral cefuroxime is changed to...... cefpodoxime (except on Pediatrics)

cephradine is changed to...... cephalexin

oxacillin is changed to...... nafcillin

meropenem is changed to...... imipenem (except on Pediatrics)

For bioequivalence

Except for patients who are unable to swallow or have NPO orders, administration of the following may be changed from intravenous to oral:

ciprofloxacindoxycycline

fluconazole linezolid

metronidazolemoxifloxacin

trimethoprim-sulfamethoxazole

voriconazole

GENERAL PRINCIPLES OF TREATMENT

1.*First, obtain cultures (see pages 7 to 9 for details)*

a)*Order routine cultures.*

b)*If necessary, perform procedures (e.g., spinal tap, pleuracentesis, arthrocentesis) necessary to obtain adequate specimens for additional cultures, and make sure that the cultures and laboratory tests on body fluids are properly ordered. The only additional tests on body fluids that are routinely helpful are cell counts, protein, glucose, Gram stain, and bacterial culture.

c)*If an invasive procedure is necessary to obtain fluid or pus for a culture, request a consultation from the appropriate subpecialist.*

2.*Then, order antibiotics (see algorithms on pages 12 to 29)*

a)*Consider the risk for resistant bacteria — use narrow spectrum therapy when possible, very broad spectrum antibiotics when necessary.*

b)Order the proper dose and frequency of antibiotics — use the patient’s age, weight, and creatinine to calculate the creatinine clearance, and consider the type, location, cause, and severity of the infection.*

For patients with community-acquired pneumonia or sepsis syndrome, this step should be completed within 4 hours of the initial contact or the onset of symptoms, and in even less time for patients with meningitis or febrile neutropenia

3.*Simultaneous with step 2, consider non-antibiotic issues and non-infectious diagnoses*

a)*Fluid resuscitation.*

b)*Drainage of abscesses and other “closed-space” infections, debridement of necrotic tissue.*

c)*Think about alternative diagnoses (e.g., ARDS vs. diffuse pneumonia, cardiogenic shock vs. septic shock).*

4.*Re-assess the patient daily*

a)*Stop antibiotics if cultures do not grow pathogens and an alternative diagnosis has been made.

b)*Either change to a narrow spectrum antibiotic when culture and susceptibility results show that one can be used (except for neutropenic oncology patients), or change to broader spectrum antibiotics if results unexpectedly show that they are necessary, or continue the initial empiric antibiotics if they are appropriate.*

PRIOR TO SELECTING ANTIBIOTICS

The following principles apply to all antibiotic algorithms – and are as important as selecting the correct empiric antibiotic(s):

Prior to the first dose of antibiotics, two blood cultures (16 to 20 mL for each culture, or 8 to 10 mL in each bottle) should be drawn, and cultures from the following sites should also be taken:

a)expectorated sputum from non-intubated patients with pneumonia

b)an endotracheal aspirate from intubated patients with pneumonia

c)debrided tissue from patients with decubitus ulcers that are infected, diabetic foot infections, or possible necrotizing fasciitis

d)cerebrospinal fluid from patients with meningismus (also send for cell count, glucose, and protein)

e)pus from aspiration or drainage of abscesses

f)at least three blood cultures from patients with suspected native valve endocarditis or infected long-term vascular access devices

g)at least four blood cultures from patients with suspected prosthetic valve endocarditis

h)pleural fluid from patients with significant pleural effusions (also send for cell count, glucose, and protein)

i)peritoneal fluid from patients with ascites (also send for cell count, glucose, and protein)

Actual tissue, pus, exudates, and other body fluids should be cultured by collection in a sterile container — swab cultures are usually either inadequate for diagnosis or provide misleading information. Even when swabs are taken from surfaces that appear infected, Gram stains cannot be done and cultures almost always grow several species of colonizing bacteria. Swabs are only for when specific bacteria are sought (e.g., group A strep in pharyngitis).
Cultures of tissues, pus, exudates, and other body fluids should be sent in anaerobic transport media when anaerobes are reasonable clinical possibilities.
Specific antibiotic dosages in this booklet are for adult patients with normal renal function. Adjustments in dosages of some antibiotics are necessary for patients with renal insufficiency. It’s always a good idea to calculate creatinine clearance prior to ordering antibiotics — can you guess the creatinine clearance of an 85 year old woman who weighs 90 lbs. and has a serum creatinine of 0.9 mg/dL? (See page 30 for the answer.)

PRIOR TO SELECTING ANTIBIOTICS

(continued)

Except for profoundly neutropenic cancer patients, empiric antibiotics should be changed to the narrowest spectrum and least expensive available agent based on final culture results — even if a patient has responded well to the empiric antibiotics.
Empiric treatment of Pseudomonas aeruginosa for community-acquired infections is generally not needed except for patients receiving high-dose steroids or recent broad-spectrum antibiotics, with a white blood cell count <1000 per mm3, or (for pneumonia) bronchiectasis or cystic fibrosis. It is not needed in patients admitted from nursing homes unless they have one of these conditions or have been on broad-spectrum antibiotics prior to admission.

Blood Cultures

Separate blood cultures means obtaining them at separate times. It is usually better to draw two blood cultures at different times for a better chance of detecting bacteremia, rather than drawing them at times that are too close to each other. The purpose of obtaining two blood cultures is to double the chance of detecting pathogens (compared to a single blood culture), as well as to distinguish pathogens from contaminants. Although some consensus guidelines state that the time interval between blood cultures should be at least 10 minutes, this is not based on data.
When native valve endocarditis is a possible diagnosis, at least three blood cultures should be obtained (over a period of several hours) because if one blood culture does not grow bacteria, two of three blood cultures with bacteria makes endocarditis much more likely than one of two blood cultures.
At least three blood cultures should be obtained from patients with permanent indwelling devices (e.g., a Hickman or Hemocath).
Whenever prosthetic valve endocarditis is a possible diagnosis, four or five blood cultures should be obtained because the likely pathogens are also likely contaminants. A patient with a prosthetic valve and coagulase-negative staphylococci growing in one of two blood cultures must be treated for endocarditis; a patient with the same bacteria in one of four blood cultures does not.
Blood cultures should not be drawn through an intravenous line except to document that catheter as the source of bacteremia. Bacteria on the catheter hub frequently contaminate these when they are drawn.

PRIOR TO SELECTING ANTIBIOTICS

(continued)

An ample volume of blood (16-20 mL per blood culture, or 8-10 mL per bottle) should be obtained because the degree of bacteremia in many patients is less than 1 bacterium per mL.
If only a small volume of blood can be obtained for culture, and anaerobes are not suspected, it is better to send only an aerobic bottle.
Coagulase-negative staphylococci (including Staphylococcus epidermidis), Corynebacterium spp., Bacillus spp., or Proprionibacterium spp. growing in only one of several blood cultures is due to contamination, not infection. Therefore, if these bacteria grow from only one blood culture, standard procedure at any laboratory is to not fully identify them unless there is a specific request based on a clear clinical need.
If an unusual species of bacteria is suspected, then it should be specified in the comments section of the laboratory order, or an infectious diseases consultation should be obtained so that the proper culture media are used in the laboratory.

Sputum cultures

Only purulent sputum should be sent for culture. Sputum that is mixed with saliva grows mixed oral flora that overgrows pathogens.

Other Cultures

Blood culture bottles are only for blood; all other body fluids should be sent in sterile containers.
Swabs are useful only when seeking a specific organism, e.g., group A strep from a throat culture. Swab specimens of wounds, decubitus ulcers, and other surfaces should not be sent for culture because bacteria always colonize these sites; instead, the tissue should be surface-sterilized, debrided, and sent for culture.
In addition to cultures, send cell counts, glucose, and protein on specimens of cerebrospinal, joint, pleural, and ascitic fluids.

CENTERS FOR MEDICARE AND MEDICAID STANDARDS

FOR THE EVALUATION AND TREATMENT OF PATIENTS ADMITTED TO THE HOSPITAL WITH COMMUNITY-ACQUIRED PNEUMONIA

THE FOLLOWING ARE REQUIRED COMPONENTS OF CAREAND ALSO MUST BE DOCUMENTED:

Blood cultures must be drawn prior to starting antibiotics.

Antibiotics must be started within four hours of the patient’s arrival at the hospital.

a)The time of arrival is the first set of vital signs (e.g., triage in the Emergency Room).