Antibiotic Selection Guide

Sunday, April 20th 2014. | Other

Antimicrobial Regimen Selection

A generally accepted systematic approach to the selection and evaluation of an antimicrobial regimen. An antimicrobial regimen is begun before the offending organism is identified, while a “definitive” regimen is instituted when the causative organism is known.
Fever is defined as a controlled elevation of body temperature above the normal range of 36.7 to 37.0°C. Fever is a manifestation of many disease states other than infection.
Many drugs have been identified as causes of fever. Drug-induced fever is defined as persistent fever in the absence of infection or other underlying condition. The fever must coincide temporally with the administration of the offending agent and disappear promptly upon its withdrawal, after which it remains normal.
Sign and Symptoms
>> White Blood Cell Count
  • Most infections result in elevated white blood cell (WBC) counts (leukocytosis) because of the mobilization of granulocytes and/or lymphocytes to destroy invading microbes. The generally accepted range of normal values for WBC counts is between 4000 and 10,000/mm3.
  • Bacterial infections are associated with elevated granulocyte counts (neutrophils, basophils), often with increased numbers of immature forms (band neutrophils) seen in peripheral blood smears (left-shift). With infection, peripheral leukocyte counts may be very high, but are rarely higher than 30,000 to 40,000/mm3. Low neutrophil counts (neutropenia) after the onset of infection indicate an abnormal response and are generally associated with a poor prognosis for bacterial infection.
  • Relative lymphocytosis, even with normal or slightly elevated total WBC counts, is generally associated with viral or fungal infections. Lymphocytopenia occurs with AIDS.
  • Many types of infections, however, may be accompanied by a completely normal WBC count and differential.
>> Pain and Inflammation
  • Pain and inflammation may accompany infection and are sometimes manifested by swelling, erythema, tenderness, and purulent drainage. Unfortunately, these signs may be apparent only if the infection is superficial or in a bone or joint.
  • The manifestations of inflammation with deep-seated infections such as meningitis, pneumonia, endocarditis, and urinary tract infection must be ascertained by examining tissues or fluids. For example, the presence of polymorphonuclear leukocytes (neutrophils) in spinal fluid, lung secretions (sputum), and urine is highly suggestive of bacterial infection.
Identification of Pathogen
  • Infected body materials must be sampled, if at all possible or practical, before the institution of antimicrobial therapy, for two reasons. First, Gram stain of the material may rapidly reveal bacteria or acid-fast stain may detect mycobacteria or actinomycetes. Second, a delay in obtaining infected fluids or tissues until after therapy is started may result in false-negative culture results or alterations in the cellular and chemical composition of infected fluids.
  • Blood cultures should be performed in the acutely ill, febrile patient. Less accessible fluids or tissues must be obtained based on localized signs or symptoms (e.g., spinal fluid in meningitis, joint fluid in arthritis). Abscesses and cellulitic areas should also be aspirated.
  • Caution must be used in the evaluation of positive culture results from normally sterile sites (e.g., blood, cerebrospinal fluid, joint fluid). The recovery of bacteria normally found on the skin in large quantities (e.g., coagulase-negative staphylococci, diphtheroids) from one of these sites may be a result of contamination of the specimen rather than a true infection.
Selection of Presumptive Therapy
  • To select rational antimicrobial therapy for a given infection, a variety of factors must be considered. These include the severity and acuity of the disease, host factors, factors related to the drugs used, and the necessity for use of multiple agents.
  • There are generally accepted drugs of choice for the treatment of most pathogens. The drugs of choice are compiled from a variety of sources and are intended as guidelines rather than specific rules for antimicrobial use.
  • When selecting antimicrobial regimens, local susceptibility data should be considered whenever possible rather than information published by other institutions or national compilations.
  • Empiric therapy is directed at organisms that are known to cause the infection in question.


Drugs of Choice, First Choice, Alternative(s)
Enterococcus faecalis (generally not as resistant to antibiotics as E. faecium)


  • Serious infection (endocarditis, meningitis, pyelonephritis with bacteremia)
  • Ampicillin (or penicillin G) + (gentamicin or streptomycin)
  • Vancomycin + (gentamicin or streptomycin), linezolid
  • Urinary tract infection (UTI)
  • Ampicillin, amoxicillin
  • Doxycyclinea fosfomycin, or nitrofurantoin

E. faecium (generally more resistant to antibiotics than E. faecalis)

  • Recommend consultation with infectious disease specialist.
  • Linezolid, quinupristin/dalfopristin

Staphylococcus aureus/Staphylococcus epidermidis

  • Methicillin (oxacillin)-sensitive
  • PRPc
  • FGC,d,e trimethoprim-sulfamethoxazole, clindamycin,f ampicillin-sulbactam, amoxicillin-clavulante, or fluoroquinolone
  • Methicillin (oxacillin)-resistant
  • Vancomycin + (gentamicin or rifampin)
  • Linezolid, quinupristin-dalfopristin, daptomycin
  • Per sensitivities: Trimethoprim-sulfamethoxazole, doxycycline,a or clindamycin

Streptococcus (groups A, B, C, G, and S. bovis)

  • Penicillin Gh or Vi or ampicillin
  • FGC,d,e erythromycin, azithromycin, clarithromycin,j S. pneumoniae
  • Penicillin-sensitive (MIC < 0.1 mcg/mL)
  • Penicillin G or V or ampicillin
  • Erythromycin, FGC,d,e azithromycin, or clarithromycinj
  • Penicillin intermediate (MIC 0.1-1.0 mcg/mL)
  • High-dose penicillin (12 million units/day for adults) or ceftriaxonee or cefotaximee
  • Gatifloxacinb, levofloxacinb, moxifloxacinb, or vancomycin
  • Penicillin-resistant (MIC ≥ 1.0 mcg/mL)
  • Recommend consultation with infectious disease specialist.
  • Vancomycin ± rifampin
  • Per sensitivities: TGC,e,k levofloxacin,b gatifloxacin,b or moxifloxacinb

Streptococcus, viridans group

  •  Penicillin G ± gentamicinl
  •  TGC,d,e erythromycin, azithromycin, clarithromycin,j or vancomycin ± gentamicin
Moraxella (Branhamella) catarrhalis

  • Amoxicillin-clavulanate, ampicillin-sulbactam
  • Trimethoprim-sulfamethoxazole, erythromycin, azithromycin, clarithromycin,j doxycycline,a SGC,e,m TGC,e,k or TGCpoe,n

Neisseria gonorrhoeae (also give concomitant treatment for Chlamydia trachomatis)

  • Disseminated gonococcal infection
  • Ceftriaxonee or cefotaximee
  • Oral follow-up: Cefixime,e cefpodoxime,e ciprofloxacin,b or ofloxacinb
  • Uncomplicated infection
  • Ceftriaxonee or cefotaxime,e cefixime,e or cefpodoximee
  • Ciprofloxacinb or ofloxacinb

N. meningitides

  • Penicillin G
  • TGCe,k

Clostridium perfringens

  • Penicillin G ± clindamycin
  • Metronidazole, clindamycin, doxycycline,a cefazolin,e imipenem,o meropenem,o or ertapenemo

C. difficile

  • Oral metronidazole
  • Oral vancomycin
Acinetobacter spp.

  • Imipenem or meropenem either ± aminoglycosidep (amikacin usually most effective)
  • Ciprofloxacin,b trimethoprim-sulfamethoxazole, or ampicillin-sulbactam

Bacteroides fragilis (and others)

  • Metronidazole
  • BLIC,g clindamycin, cephamycin,e,q or carbapenemo

Enterobacter spp.

  • Imipenem, meropenem, ertapenem, or cefepime ± aminoglycosidep
  • Ciprofloxacin,b levofloxacin,b piperacillin-tazobactam, ticarcillin-clavulanate, or trimethoprim-sulfamethoxazole

Escherichia coli

  • Meningitis
  • TGCe,k or meropenem
  • Systemic infection
  • TGCe,k
  • Ampicillin-sulbactam, FGC,d,e BL/BLI,g trimethoprim-sulfamethoxazole, SGC,e,m fluoroquinolone,b,o,r imipenem,o meropenemo
  • Urinary tract infection
  • Most oral agents: Check sensitivities.
  • Ampicillin, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, or cephalexine
  • Aminoglycoside, FGCd,e nitrofurantoin, fluoroquinoloneb,o,r

Gardnerella vaginalis

  • Metronidazole
  • Clindamycin

Hemophilus influenzae

  • Meningitis
  • Cefotaximee or ceftriaxonee
  • Meropenemo or chloramphenicolr
  • Other infections
  • BLIC,g or if β-lactamase-negative, ampicillin or amoxicillin
  • Trimethoprim-sulfamethoxazole, cefuroxime,e erythromycin, azithromycin, clarithromycin,j or fluoroquinoloneb,o,r

Klebsiella pneumoniae

  • TGCe,k (if UTI only: Aminoglycosidep)
  • Trimethoprim-sulfamethoxazole, cefuroxime,e fluoroquinolone,b,r BLIC,g imipenem,o or meropenemo
  • Legionella spp.
  • Erythromycin ± rifampin or fluoroquinoloneb,r
  • Trimethoprim-sulfamethoxazole, clarithromycin,j azithromycin, or doxycyclinea

Pasteurella multocida

  • Penicillin G, ampicillin, amoxicillin
  • Doxycycline,a BLIC,g trimethoprim-sulfamethoxazole or ceftriaxonee,k

Proteus mirabilis

  • Ampicillin
  • Trimethoprim-sulfamethoxazole, most antibiotics except PRPc

Proteus (indole-positive) (including Providencia rettgeri, Morganella morganii, and Proteus vulgaris)

  • TGCe,k or fluoroquinoloneb,r
  • Trimethoprim-sulfamethoxazole, BLIC,g aztreonam,t imipenem,o or TGCpoe,n

Providencia stuartii

  • TGCe,k or fluoroquinoloneb,r
  • Trimethoprim-sulfamethoxazole, aztreonam,t imipenem,o or meropenemo

Pseudomonas aeruginosa

  • Cefepime, ceftazidime, piperacillin-tazobactam, or ticarcillin-clavulanate plus aminoglycosidep
  • Ciprofloxacin,b levofloxacin,b aztreonam,t imipenem,o or meropenemo
  • UTI only: Aminoglycosidep
  • Ciprofloxacin,b levofloxacin,b or gatifloxacinb

Salmonella typhi

  • Ciprofloxacin,b levofloxacin,b ceftriaxone,e or cefotaximee
  • Trimethoprim-sulfamethoxazole

Serratia marcescens

  • Piperacillin-tazobactam, ticarcillin-clavulanate, or TGC,e,k± gentamicin
  • Trimethoprim-sulfamethoxazole, ciprofloxacin,b levofloxacin,b aztreonam,t imipenem,g meropenem,a or ertapenem

Stenotrophomonas (Xanthomonas) maltophilia

  •  Trimethoprim-sulfamethoxazole
  • Generally very resistant to all antimicrobials; check sensitivities to ceftazidime,e ticarcillin-clavulanate, doxycycline,a and minocyclinea
Chlamydia pneumoniae

  •    Doxycyclinea
  •    Erythromycin, azithromycin, clarithromycin,j or fluoroquinoloneb,r

C. trachomatis

  •    Doxycyclinea or azithromycin
  •    Levofloxacinb or ofloxacinb

Mycoplasma pneumoniae

  •    Erythromycin, azithromycin, clarithromycinj
  •    Doxycyclinea or fluoroquinoloneb,r
Treponema pallidum

  •    Neurosyphilis
  •    Penicillin G
  •    Ceftriaxonee
  •    Primary or secondary
  •    Benzathine penicillin G
  •    Doxycyclinea or ceftriaxonee

Borrelia burgdorferi (choice depends on stage of disease)

  •    Ceftriaxonee or cefuroxime axetil,e doxycycline,a amoxicillin
  •    High-dose penicillin, cefotaxime,e azithromycin, or clarithromycinj


= In evaluating a patient for initial or empiric therapy, the following factors should be considered:
  • Allergy or history of adverse drug reactions
  • Age of patient
  • Pregnancy
  • Metabolic abnormalities
  • Renal and hepatic function
  • Concomitant drug therapy
  • Concomitant disease states
= Patients with diminished renal and/or hepatic function will accumulate certain drugs unless dosage is adjusted. Any concomitant therapy the patient is receiving may influence the selection of drug therapy, the dose, and monitoring.
  • Integration of both pharmacokinetic and pharmacodynamic properties of an agent is important when choosing antimicrobial therapy to ensure efficacy and prevent resistance.
  • The importance of tissue penetration varies with the site of infection. The central nervous system (CNS) is one body site where the importance of antimicrobial penetration is relatively well defined and correlations with clinical outcomes are established. Drugs that do not reach significant concentrations in cerebrospinal fluid (CSF) should be avoided in treating meningitis.
  • Apart from the bloodstream, other body fluids where drug concentration data are clinically relevant include urine, synovial fluid, and peritoneal fluid.
  • Certain pharmacokinetic parameters such as area under the concentration-time curve (AUC) and maximal plasma concentration (Cmax can be predictive of treatment outcome when specific ratios of AUC or Cmax to the minimum inhibitory concentration (MIC) are achieved. For some agents, the ratio of AUC to MIC, peak to MIC ratio, or the time that the drug concentration is above the MIC may predict efficacy.
  • Antimicrobials that affect cell wall synthesis (e.g., β-lactams and vancomycin) display time-dependent bactericidal effects. Therefore, the most important pharmacodynamic relationship for these antimicrobials is the duration that drug concentrations exceed the MIC (T greater than MIC).
  • The costs of drug therapy are increasing dramatically, especially as new products derived from biotechnology are introduced. The total cost of antimicrobial therapy includes much more than just the acquisition cost of the drugs.
  • The achievement of synergistic antimicrobial activity is advantageous for infections caused by gram-negative bacilli in immunosuppressed patients.
  • Traditionally, combinations of aminoglycosides and β-lactams have been used since these drugs together generally act synergistically against a wide variety of bacteria. However, the data supporting superior efficacy of synergistic over nonsynergistic combinations are weak.
  • Synergistic combinations may produce better results in infections caused by Pseudomonas aeruginosa, in certain infections caused by Enterococcus spp., and, perhaps, in patients with profound, persistent neutropenia.
The use of combinations to prevent the emergence of resistance is widely applied but not often realized. The only circumstance where this has been clearly effective is in the treatment of tuberculosis.
  • Although there are potentially beneficial effects from combining drugs, there are also potentially serious liabilities. Examples include additive nephrotoxicity from drugs such as aminoglycosides, amphotericin, and possibly vancomycin. Inactivation of aminoglycosides by penicillins may be clinically significant when excessive doses of penicillin are given to a patient in renal failure.
  • Some combinations of antimicrobials are potentially antagonistic. Such combinations should probably be avoided whenever possible, unless the clinical situation warrants the use of both drugs for different pathogens. Agents that are capable of inducing β-lactamase production in bacteria may antagonize the effects of enzyme-labile drugs such as penicillins.
A variety of factors may be responsible for apparent lack of response to therapy. Factors include those directly related to the host, those related to the pathogen, and, although unlikely, laboratory error in identification and/or susceptibility testing. Factors directly related to the antimicrobial agents being utilized are only a small proportion of the possibilities.
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