infectious diseases
Overview of Antibacterial Drugs
Selection and Use of Antibiotics
Antibiotics should be used only if clinical or laboratory evidence suggests bacterial infection. Use for viral illness or undifferentiated fever is inappropriate in most cases; it exposes patients to drug complications without any benefit and contributes to bacterial resistance. Certain bacterial infections (eg, abscesses, infections with foreign bodies) require surgical intervention and do not respond to antibiotics alone. In general, clinicians should try to use antibiotics with the narrowest spectrum of activity and for the shortest duration. Cultures and antibiotic susceptibility testing are essential for selecting a drug for serious infections. However, treatment must often begin before culture results are available, necessitating selection according to the most likely pathogens (empiric antibiotic selection). Whether chosen according to culture results or not, drugs with the narrowest spectrum of activity that can control the infection should be used. For empiric treatment of serious infections that may involve any one of several pathogens (eg, fever in neutropenic patients) or that may be due to multiple pathogens (eg, polymicrobial anaerobic infection), a broad spectrum of activity is desirable. The most likely pathogens and their susceptibility to antibiotics vary according to geographic location (within cities or even within a hospital) and can change from month to month. Susceptibility data should be compiled into antibiograms and used to direct empiric treatment whenever possible. Antibiograms summarize regional facility–specific (or location–specific) antibiotic susceptibility patterns of common pathogens to commonly used antibiotics. is usually defined as a more rapid and complete bactericidal action from a combination of antibiotics than occurs with either antibiotic alone. A common example is a cell wall–active antibiotic (eg, a Beta-Lactams , In vivoantibiotic effectiveness is affected by many factors, including Overview of Pharmacokinetics : The time course of antibiotic levels, which are affected by factors such as Overview of Pharmacodynamics : The antimicrobial activity of local antibiotic concentrations on the target pathogen and that pathogen's response including resistance Presence of foreign materials Control of source of infection Drug Interactions or inhibiting substances Host Defense Mechanisms Against Infection None Bactericidaldrugs kill bacteria.Bacteriostaticdrugs slow or stop in vitro bacterial growth. These definitions are not absolute; bacteriostatic drugs may kill some susceptible bacterial species, and bactericidal drugs may only inhibit growth of some susceptible bacterial species. More precise quantitative methods identify the minimum in vitro concentration at which an antibiotic can inhibit growth (minimum inhibitory concentration [MIC]) or kill (minimum bactericidal concentration [MBC]). An antibiotic with bactericidal activity may improve bacterial killing when host defenses are impaired locally at the site of infection (eg, in meningitis or endocarditis) or systemically (eg, in patients who are neutropenic or immunocompromised in other ways). However, there are limited clinical data indicating that a bactericidal drug should be selected over a bacteriostatic drug simply on the basis of that classification. Drug selection for optimal efficacy should be based on how the drug concentration varies over time in relation to the MIC rather than whether the drug has bactericidal or bacteriostatic activity. Antibiotics can be grouped into 3 general categories ( Effectiveness reference ) based on the pharmacokinetics that optimizes antimicrobial activity (pharmacodynamics): Concentration-dependent: Themagnitudeby which the peak concentration exceeds the MIC (typically expressed as the peak-to-MIC ratio) best correlates with antimicrobial activity Time-dependent: Thedurationof the dosing interval in which the antibiotic concentration exceeds the MIC (typically expressed as the percentage of time above MIC) best correlates with antimicrobial activity Exposure-dependent: Theamount of druggiven relative to the MIC (the amount of drug is the 24-hour area under the concentration-time curve [AUC24]; the AUC24-to-MIC ratio best correlates with antimicrobial activity) Aminoglycosides , Beta-Lactams , Most antimicrobials have exposure-dependent antibacterial activity best characterized by the AUC-to-MIC ratio.Vancomycin, tetracyclines,andclindamycinare examples. There are 3 pharmacokinetic/pharmacodynamic parameters related to antimicrobial efficacy: Ratio of peak serum concentration to MIC Percent time above MIC Ratio of 24-hour AUC to MIC 1.A PK/PD Approach to Antibiotic Therapy. RxKinetics. Accessed 05/04/22. For many antibiotics, oral administration results in therapeutic blood levels nearly as rapidly as IV administration. However, IV administration of orally available drugs is preferred in the following circumstances: Oral antibiotics cannot be tolerated (eg, because of vomiting). Oral antibiotics are poorly absorbed (eg, because of malabsorption after intestinal surgery, impaired intestinal motility [eg, due to opioid use]). Patients are critically ill, possibly impairing gastrointestinal tract perfusion or making even the brief delay with oral administration detrimental. Doses and scheduling of antibiotics may need to be adjusted for the following: Antibiotics in Neonates None Overview of Drug Therapy in Older Adults None Patients with renal failure (see table Usual Dosages of Commonly Prescribed Antibiotics[a] ) Patients with hepatic insufficiency (most commonly for cefoperazone,chloramphenicol,metronidazole,rifabutin, andrifampin) Obese patients Patients with cystic fibrosis Pregnancy and breastfeedingaffect choice of antibiotic. Penicillins, cephalosporins, anderythromycinare among the safest antibiotics during pregnancy; tetracyclines are contraindicated. Most antibiotics reach sufficient concentrations in breast milk to affect a breastfed baby, sometimes contraindicating their use in women who are breastfeeding. Antibiotics should be continued until objective evidence of systemic infection (eg, fever, symptoms, abnormal laboratory findings) is absent for several days. For some infections (eg, Infective Endocarditis , Complications of antibiotic therapy include superinfection by nonsusceptible bacteria or fungi and cutaneous, renal, hematologic, neurologic, and gastrointestinal adverse effects. Adverse effects frequently require stopping the causative drug and substituting another antibiotic to which the bacteria are susceptible; sometimes, no alternatives exist. 