GENERAL ANTIBIOTIC PRESCRIBING PITFALLS

Despite the ability of antimicrobial therapy to prevent and control infection, prescribing errors are common, including treatment of colonization, suboptimal empiric therapy, inappropriate combination therapy, dosing and duration errors, and mismanagement of apparent antibiotic failure. Inadequate consideration of antibiotic resistance potential, tissue penetration, drug interactions, side effects, and cost may limit the effectiveness of antimicrobial therapy.

PITFALL: CHOOSING ANTIBIOTIC THERAPY BASED SOLELY ON SPECTRUM

Antibiotic spectrum is the first consideration in selecting antimicrobial therapy, but is only one of several factors and does not assure clinical effectiveness. Antibiotics that are effective against a microorganism in-vitro but unable to reach the site of infection are of no benefit to the host, emphasizing the importance of antibiotic tissue penetration. For example, even though most urinary tract infections are caused by the same pathogens, drugs for catheter-associated bacteriuria and cystitis differ from those used for pyelonephritis, prostatitis, or epididymitis due to differing abilities to penetrate target tissues. Antibiotic tissue penetration depends on properties of the antibiotic (e.g., lipid solubility, molecular size) and tissue (e.g, adequacy of blood supply, presence of inflammation). Antibiotic tissue penetration is rarely problematic early in acute infections due to increased microvascular permeability from local release of chemical inflammatory mediators. However, antibiotic therapy of chronic infections (e.g., chronic pyelonephritis, chronic prostatitis, chronic osteomyelitis) and infections caused by intracellular pathogens often rely on chemical properties of an antibiotic (e.g., high lipid solubility, small molecular size) for adequate tissue penetration. Antibiotics cannot be expected to eradicate organisms from areas that are difficult to penetrate or have impaired blood supply, such as abscesses, which usually require surgical drainage for cure. In addition, implanted foreign materials associated with infection usually need to be removed for cure, since microbes causing infections associated with prosthetic joints, shunts, and intravenous lines produce a slime/glycocalyx on plastic/metal surfaces that permits organisms to survive despite antimicrobial therapy. Remember, after antimicrobial spectrum, "tissue is the issue!"

PITFALL: PROLONGED USE OF IV ANTIBIOTICS IN HOSPITALIZED PATIENTS

Most hospitalized patients on IV therapy able to take PO medications should be switched to PO equivalent therapy soon after clinical improvement (usually < 72 hours). Advantages of early IV-to-PO switch programs include early hospital discharge, less need for home IV therapy, and virtual elimination of IV line infections. In addition, switching early from IV to PO antibiotics is the single most important cost saving strategy in hospitalized patients, as the institutional cost of IV administration (~ $10/dose) may exceed the cost of the antibiotic itself. (Antibiotic costs can also be minimized by using antibiotics with long half-lives, and by choosing monotherapy over combination therapy.) Drugs well-suited for IV-to-PO switch or for treatment entirely by the oral route include doxycycline, minocycline, clindamycin, metronidazole, chloramphenicol, amoxicillin, trimethoprim-sulfamethoxazole, levofloxacin, gatifloxacin, moxifloxacin, and linezolid. Only some penicillins and cephalosporins are useful for IV-to-PO switch programs, due to limited bioavailability.

Most infectious diseases should be treated orally, unless the patient is critically ill, cannot take antibiotics by mouth, or there is no equivalent oral antibiotic. If the patient is able to take/absorb oral antibiotics, there is no difference in clinical outcome using equivalent IV or PO antibiotics. It is more important to think in terms of antibiotic spectrum, bioavailability and tissue penetration, rather than route of administration. Nearly all non-critically ill patients should be treated in part or entirely with oral antibiotics. When switching from IV to PO therapy, the oral antibiotic chosen ideally should achieve the same blood and tissue levels as the equivalent IV antibiotic.

PITFALL: OVERRELIANCE ON MICROBIOLOGY SUSCEPTIBILITY TESTING

In-vitro susceptibility testing provides information about microbial sensitivities to various antibiotics, and is useful in guiding therapy. Proper application of microbiology and susceptibility data requires careful assessment of the in-vitro results to determine if they are consistent with the clinical context; if not, the clinical impression should take precedence. Limitations of microbiology susceptibility testing include:

1.  In-vitro data do not differentiate between colonizers and pathogens. Before treating a culture report from the microbiology laboratory, it is important to determine whether the organism is a pathogen or a colonizer in the clinical context. As a rule, colonization should not be treated. Before treating a culture report from the microbiology laboratory, it is important to determine whether the organism is a pathogen or a colonizer in the clinical context. As a rule, colonization should not be treated. Before treating a culture report from the microbiology laboratory, it is important to determine whether the organism is a pathogen or a colonizer in the clinical context. As a rule, colonization should not be treated.

2.  In-vitro data do not necessarily translate into in-vivo efficacy. Reports which indicate an organism is "sensitive" or "resistant" to a given antibiotic in-vitro do not necessarily reflect in-vivo activity. The table below lists antibiotic-microorganism combinations for which susceptibility testing is usually unreliable. Reports which indicate an organism is "sensitive" or "resistant" to a given antibiotic in-vitro do not necessarily reflect in-vivo activity. The table below lists antibiotic-microorganism combinations for which susceptibility testing is usually unreliable. Reports which indicate an organism is "sensitive" or "resistant" to a given antibiotic in-vitro do not necessarily reflect in-vivo activity. The table below lists antibiotic-microorganism combinations for which susceptibility testing is usually unreliable.

3.  In-vitro susceptibility testing is dependent on the microbe, methodology, and antibiotic concentration. In-vitro susceptibility testing by the microbiology laboratory assumes the isolate was recovered from blood, and is being exposed to serum concentrations of an antibiotic given in the usual dose. Since some body sites (e.g., bladder, urine) contain higher antibiotic concentrations than found in serum, and other body sites (e.g., CSF) contain lower antibiotic concentrations than found in serum, in-vitro data may be misleading for non-bloodstream infections. For example, a Klebsiella pneumoniae isolate obtained from the CSF may be reported as "sensitive" to cefazolin even though cefazolin does not penetrate the CSF. Likewise, E. coli and Klebsiella urinary isolates are often reported as "resistant" to ampicillin/sulbactam despite in-vivo efficacy, due to high antibiotic concentrations in the urinary tract. Because microbial susceptibility is concentration-dependent, antibiotics should be prescribed at the usual recommended doses. Attempts to lower cost by reducing dosage may decrease antibiotic efficacy (e.g., cefoxitin 2 gm IV inhibits ~ 85% of B. fragilis isolates, whereas 1 gm IV inhibits only ~ 20% of strains).In-vitro susceptibility testing by the microbiology laboratory assumes the isolate was recovered from blood, and is being exposed to serum concentrations of an antibiotic given in the usual dose. Since some body sites (e.g., bladder, urine) contain higher antibiotic concentrations than found in serum, and other body sites (e.g., CSF) contain lower antibiotic concentrations than found in serum, in-vitro data may be misleading for non-bloodstream infections. For example, a Klebsiella pneumoniae isolate obtained from the CSF may be reported as "sensitive" to cefazolin even though cefazolin does not penetrate the CSF. Likewise, E. coli and Klebsiella urinary isolates are often reported as "resistant" to ampicillin/sulbactam despite in-vivo efficacy, due to high antibiotic concentrations in the urinary tract. Because microbial susceptibility is concentration-dependent, antibiotics should be prescribed at the usual recommended doses. Attempts to lower cost by reducing dosage may decrease antibiotic efficacy (e.g., cefoxitin 2 gm IV inhibits ~ 85% of B. fragilis isolates, whereas 1 gm IV inhibits only ~ 20% of strains).In-vitro susceptibility testing by the microbiology laboratory assumes the isolate was recovered from blood, and is being exposed to serum concentrations of an antibiotic given in the usual dose. Since some body sites (e.g., bladder, urine) contain higher antibiotic concentrations than found in serum, and other body sites (e.g., CSF) contain lower antibiotic concentrations than found in serum, in-vitro data may be misleading for non-bloodstream infections. For example, a Klebsiella pneumoniae isolate obtained from the CSF may be reported as "sensitive" to cefazolin even though cefazolin does not penetrate the CSF. Likewise, E. coli and Klebsiella urinary isolates are often reported as "resistant" to ampicillin/sulbactam despite in-vivo efficacy, due to high antibiotic concentrations in the urinary tract. Because microbial susceptibility is concentration-dependent, antibiotics should be prescribed at the usual recommended doses. Attempts to lower cost by reducing dosage may decrease antibiotic efficacy (e.g., cefoxitin 2 gm IV inhibits ~ 85% of B. fragilis isolates, whereas 1 gm IV inhibits only ~ 20% of strains).

 PITFALL: USE OF ANTIBIOTICS FOR PERSISTENT FEVERS