Antibiotic Selection Guide
- 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 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.
- 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.
- 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.
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
- 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 â‰¥ 1.0 mcg/mL)
- Recommend consultation with infectious disease specialist.
- Vancomycin Â± rifampin
- Per sensitivities: TGC,e,k levofloxacin,b gatifloxacin,b or moxifloxacinb
Streptococcus, viridans group
- Penicillin G Â± gentamicinl
- TGC,d,e erythromycin, azithromycin, clarithromycin,j or vancomycin Â± 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
- Penicillin G
- Penicillin G Â± clindamycin
- Metronidazole, clindamycin, doxycycline,a cefazolin,e imipenem,o meropenem,o or ertapenemo
- Oral metronidazole
- Oral vancomycin
- Imipenem or meropenem either Â± aminoglycosidep (amikacin usually most effective)
- Ciprofloxacin,b trimethoprim-sulfamethoxazole, or ampicillin-sulbactam
Bacteroides fragilis (and others)
- BLIC,g clindamycin, cephamycin,e,q or carbapenemo
- Imipenem, meropenem, ertapenem, or cefepime Â± aminoglycosidep
- Ciprofloxacin,b levofloxacin,b piperacillin-tazobactam, ticarcillin-clavulanate, or trimethoprim-sulfamethoxazole
- TGCe,k or meropenem
- Systemic infection
- 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
- Cefotaximee or ceftriaxonee
- Meropenemo or chloramphenicolr
- Other infections
- BLIC,g or if Î²-lactamase-negative, ampicillin or amoxicillin
- Trimethoprim-sulfamethoxazole, cefuroxime,e erythromycin, azithromycin, clarithromycin,j or fluoroquinoloneb,o,r
- TGCe,k (if UTI only: Aminoglycosidep)
- Trimethoprim-sulfamethoxazole, cefuroxime,e fluoroquinolone,b,r BLIC,g imipenem,o or meropenemo
- Legionella spp.
- Erythromycin Â± rifampin or fluoroquinoloneb,r
- Trimethoprim-sulfamethoxazole, clarithromycin,j azithromycin, or doxycyclinea
- Penicillin G, ampicillin, amoxicillin
- Doxycycline,a BLIC,g trimethoprim-sulfamethoxazole or ceftriaxonee,k
- 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
- TGCe,k or fluoroquinoloneb,r
- Trimethoprim-sulfamethoxazole, aztreonam,t imipenem,o or meropenemo
- 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
- Ciprofloxacin,b levofloxacin,b ceftriaxone,e or cefotaximee
- Piperacillin-tazobactam, ticarcillin-clavulanate, or TGC,e,kÂ± gentamicin
- Trimethoprim-sulfamethoxazole, ciprofloxacin,b levofloxacin,b aztreonam,t imipenem,g meropenem,a or ertapenem
Stenotrophomonas (Xanthomonas) maltophilia
- Generally very resistant to all antimicrobials; check sensitivities to ceftazidime,e ticarcillin-clavulanate, doxycycline,a and minocyclinea
- Erythromycin, azithromycin, clarithromycin,j or fluoroquinoloneb,r
- Doxycyclinea or azithromycin
- Levofloxacinb or ofloxacinb
- Erythromycin, azithromycin, clarithromycinj
- Doxycyclinea or fluoroquinoloneb,r
- Penicillin G
- 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
- Allergy or history of adverse drug reactions
- Age of patient
- Metabolic abnormalities
- Renal and hepatic function
- Concomitant drug therapy
- Concomitant disease states
- 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., Î²-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 Î²-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.
- 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 Î²-lactamase production in bacteria may antagonize the effects of enzyme-labile drugs such as penicillins.