ANTI-INFECTIVE THERAPY/ 7 4. Take into Account Previous Antibiotic Treatment tic. The use of rifampin combined with oxacillin is The remarkable adaptability of bacteria makes it antagonistic in some strains of S. aureus for exam- highly likely that a new pathogen will be resistant to ple. Many combination regimens have not been previously administered antibiotics. If the onset of the completely studied, and the natural assumption that new infection was preceded by a significant interval nore antibiotics lead to more killing power often does not apply when antibiotics were not given, the resident fora may b. Use of multiple antibiotics increases the risk of re-establishment of normal fora can take weeks, and adverse reactions. Drug allergies are common patients in hospital are likely to recolonize with highly When a patient re than one antibiotic devel resistant hospital ps an allergic reaction, all antibiotics become itial offenders, and these 5. Take into Consideration Important Host Factors be used. In some instances, combination therapy a. Penetration into the site of infection. For example, can increase the risk of toxicity. The combination of patients with bacterial meningitis should not be gentamicin and vancomycin increases the risk of treated with antibiotics that fail to cross the nephrotoxicity, for example blood-brain barrier(examples include 1st-generation Use of multiple antibiotics often increases costs cep losporins, gentamicin, and clindamycin) and the risk of administration errors. Administra on of two or more intravenous antibiotics requires b. Peripheral WBC count. Patients with neutropenia have a high mortality rate from sepsis. Immediate multiple intravenous reservoirs, lines, and pumps Nurses and pharmacists must dispense each antibi broad-spectrum, high-dose intravenous antibiotic otic dose, increasing labor costs. The more drugs a treatment is recommended py for patient receives, the higher the probability of an these patients administration error. Use of two or more drugs usu- c. Age and underlying diseases(hepatic and renal ally increases the acquisition costs dysfunction). Elderly patients tend to metabolize d. Use of multiple antibiotics the risk of and excrete antibiotics more slowly; longer dosing intervals are therefore often required. Agents with infection with highly resistant organisms. Pro- significant toxicity (such as aminoglycosides longed use of broad-spectrum antibiotic coverage increases the risk of infection with MRSA, vre should generally be avoided in elderly patients because they exhibit greater toxicity. Antibiotics multiresistant gram-negative bacilli, and fungi When multiple antibiotics are used, the spectrum metabolized primarily by the liver should generally of bacteria killed increases. Killing most of the be avoided or reduced in patients with significant rrhosis. In renal dy normal fora in the pharynx and gastrointestinal function, antibiotic doses need to be modified ract is harmful to the host. The normal flora ompete for nutrients, occupy binding sites that d. Duration of hospitalization Patients who have could otherwise be used by pathe bacteria and produce agents that inhibit the growth of community-acquired pat patients who have ompetitors. Loss of the normal fora allows resis- been in the hospital for prolonged periods and have tant pathogens to overgrow received several courses of antibiotics tend to be col- onized with highly resistant bacteria and with fungi. 7. Switch to Narrower-Spectrum Antibiotic Coverage e. Severity of the patient's illness. The severely ill Within 3 Days patient who is toxic and hypotensive requires broad-(Table 1. 1, Figure 1.5 ). Within 3 days following the new fever without other serious can usually be observed off antibiotic nic complaints mouth flora reveal that the numbers and types of bac- teria begin to change significantly. The normal Aora 6. Use the Fewest Drugs Possible die, and resistant gram-negative rods, gram-positive cocci,and fungi begin to predominate. The more Multiple drugs may lead to antagonism rather quickly the selective pressures of broad-spectrum than synergy. Some regi ens, such as overage can be discontinued, the lower the and an aminoglycoside for Enterococcus, have been risk of selecting for highly resistant pathogens.Broad shown to result in synergy-that is, the combined coverage is reasonable as initial empiric therapy until effects are greater than simple addition of the MBCs cultures are available. By the 3rd day, the microbiology of the two agents would suggest. In other instances, laboratory can generally identify the pathogen or certain C have proved to be antagonis- pathogens, and a narrower-spectrum, specific antibiotic4. Take into Account Previous Antibiotic Treatment The remarkable adaptability of bacteria makes it highly likely that a new pathogen will be resistant to previously administered antibiotics. If the onset of the new infection was preceded by a significant interval when antibiotics were not given, the resident flora may have recolonized with less resistant flora. However, the re-establishment of normal flora can take weeks, and patients in hospital are likely to recolonize with highly resistant hospital flora. 5. Take into Consideration Important Host Factors a. Penetration into the site of infection. For example, patients with bacterial meningitis should not be treated with antibiotics that fail to cross the blood–brain barrier (examples include 1st-generation cephalosporins, gentamicin, and clindamycin). b. Peripheral WBC count. Patients with neutropenia have a high mortality rate from sepsis. Immediate broad-spectrum, high-dose intravenous antibiotic treatment is recommended as empiric therapy for these patients. c. Age and underlying diseases (hepatic and renal dysfunction). Elderly patients tend to metabolize and excrete antibiotics more slowly; longer dosing intervals are therefore often required. Agents with significant toxicity (such as aminoglycosides) should generally be avoided in elderly patients because they exhibit greater toxicity. Antibiotics metabolized primarily by the liver should generally be avoided or reduced in patients with significant cirrhosis. In patients with significant renal dys￾function, antibiotic doses need to be modified. d. Duration of hospitalization. Patients who have just arrived in the hospital tend to be colonized with community-acquired pathogens; patients who have been in the hospital for prolonged periods and have received several courses of antibiotics tend to be col￾onized with highly resistant bacteria and with fungi. e. Severity of the patient’s illness. The severely ill patient who is toxic and hypotensive requires broad￾spectrum antibiotics; the patient who simply has a new fever without other serious systemic complaints can usually be observed off antibiotics. 6. Use the Fewest Drugs Possible a. Multiple drugs may lead to antagonism rather than synergy. Some regimens, such as penicillin and an aminoglycoside for Enterococcus, have been shown to result in synergy—that is, the combined effects are greater than simple addition of the MBCs of the two agents would suggest. In other instances, certain combinations have proved to be antagonis￾tic. The use of rifampin combined with oxacillin is antagonistic in some strains of S. aureus, for exam￾ple. Many combination regimens have not been completely studied, and the natural assumption that more antibiotics lead to more killing power often does not apply. b. Use of multiple antibiotics increases the risk of adverse reactions. Drug allergies are common. When a patient on more than one antibiotic devel￾ops an allergic reaction, all antibiotics become potential offenders, and these agents can no longer be used. In some instances, combination therapy can increase the risk of toxicity. The combination of gentamicin and vancomycin increases the risk of nephrotoxicity, for example. c. Use of multiple antibiotics often increases costs and the risk of administration errors. Administra￾tion of two or more intravenous antibiotics requires multiple intravenous reservoirs, lines, and pumps. Nurses and pharmacists must dispense each antibi￾otic dose, increasing labor costs. The more drugs a patient receives, the higher the probability of an administration error. Use of two or more drugs usu￾ally increases the acquisition costs. d. Use of multiple antibiotics increases the risk of infection with highly resistant organisms. Pro￾longed use of broad-spectrum antibiotic coverage increases the risk of infection with MRSA, VRE, multiresistant gram-negative bacilli, and fungi. When multiple antibiotics are used, the spectrum of bacteria killed increases. Killing most of the normal flora in the pharynx and gastrointestinal tract is harmful to the host. The normal flora compete for nutrients, occupy binding sites that could otherwise be used by pathogenic bacteria, and produce agents that inhibit the growth of competitors. Loss of the normal flora allows resis￾tant pathogens to overgrow. 7. Switch to Narrower-Spectrum Antibiotic Coverage Within 3 Days (Table 1.1, Figure 1.5). Within 3 days following the administration of antibiotics, sequential cultures of mouth flora reveal that the numbers and types of bac￾teria begin to change significantly. The normal flora die, and resistant gram-negative rods, gram-positive cocci, and fungi begin to predominate. The more quickly the selective pressures of broad-spectrum antibiotic coverage can be discontinued, the lower the risk of selecting for highly resistant pathogens. Broad coverage is reasonable as initial empiric therapy until cultures are available. By the 3rd day, the microbiology laboratory can generally identify the pathogen or pathogens, and a narrower-spectrum, specific antibiotic ANTI-INFECTIVE THERAPY / 7