Antibacterial therapy: principles

40. Antibacterial therapy


principles




Antimicrobial chemotherapy exploits the differences between microorganisms and host cells. Agents that attack targets unique to microorganisms are thus relatively safe to the host—the concept of ‘selective toxicity’. Strictly speaking, the term ‘antibiotic’ refers to naturally occurring products that inhibit or kill microorganisms. It is, however, often used to describe chemically modified or synthetic agents that would be more correctly called antibacterial or antimicrobial agents.


Antibacterial drugs may be classified by their spectrum of antibacterial activity (Ch. 41) or their target site of action (Fig. 3.40.1 and Table 3.40.1).



Table 3.40.1 CLASSES OF ANTIBACTERIAL DRUG































































































Target site and class Examples Comments/adverse reactions
Cell wall (β-lactams)    
Penicillins (β-lactams) Benzylpenicillin, ampicillin Generally safe but allergic reactions
Cephalosporins (β-lactams) Cephalexin, cefuroxime, ceftazidime Broad-spectrum: overusage promotes resistance
Carbapenems (β-lactams) Imipenem, meropenem Reserved for resistant pathogens
Glycopeptides Vancomycin, teicoplanin Vancomycin may be nephro/oto-toxic, assay required
Protein synthesis    
Aminoglycosides Gentamicin, amikacin Potential nephro- and oto-toxicity; assay required
Tetracyclines Tetracycline, doxycycline Stain teeth and bone
Chloramphenicol Chloramphenicol Potential marrow toxicity
Macrolides Erythromycin Often used in penicillin-allergic patients
Lincosamides Clindamycin Associated with pseudomembranous colitis
Fusidic acidOxazolidinones Fusidic acidLinezolid May cause jaundiceMay cause myelosuppression
Nucleic acid synthesis    
Sulphonamides Sulfamethoxazole Rarely used because of toxic reactions
Trimethoprim Trimethoprim Mainly used in treatment of UTI
Quinolones Nalidixic acid, ciprofloxacin Early quinolones have limited Gram-positive activity
Rifamycins Rifampicin Stains tears/urine, may cause jaundice
NitroimidazolesNitrofurans MetronidazoleNitrofurantoin Antabuse effect with alcoholUrinary activity only
Cell membrane function    
Polymyxins Colistin Used for bowel decontamination or by inhalation
Cyclic lipopeptide Daptomycin May cause rhabdomyolysis
  Ethambutol Visual changes

UTI, urinary tract infection.


Agents that inhibit bacterial growth are termed bacteriostatic, whereas those that kill bacteria are termed bactericidal. For many agents, bactericidal activity is species dependent and generally not essential except in some immunosuppressed individuals and in endocarditis. However classification by pharmacodynamic properties, such as concentration- or time-dependent killing, is coming into use for dosage decisions (Ch. 41).



Antimicrobial resistance


A bacterium is considered resistant to a certain agent when bacterial growth cannot be inhibited by achievable serum concentrations of the agent. The minimal inhibitory concentration (MIC) is the antibiotic concentration required to suppress visible growth. In diagnostic microbiology laboratories, the disc diffusion method is used to determine resistance, whereby a certain diameter for the inhibition zone corresponds to the MIC (Fig. 3.40.2). Some bacteria show inherent or innate resistance to certain antibiotics (e.g. Pseudomonas aeruginosa is always resistant to benzylpenicillin). Other bacteria have acquired resistance as a result of genetic change. Resistance may result from chromosomal mutation or transformation (Fig. 3.40.3). Spontaneous mutation of the chromosome may change protein synthesis to create bacteria that have a selective advantage and will, therefore, outgrow the susceptible population. Certain species such as Streptococcus viridans, Neisseria and Haemophilus spp. can pick up genes from dead bacteria and transform their corresponding gene with the newly acquired DNA sequence, resulting, for example, in penicillin-resistant pneumococci.


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Jul 3, 2016 | Posted by in MUSCULOSKELETAL MEDICINE | Comments Off on Antibacterial therapy: principles

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