Principles of antimicrobial treatment
Antimicrobials may be used to prevent (Prophylaxis above) or treat established wound infection. The use of antibiotics for established infection in wounds ideally requires the isolation of the bacterium and a determination of its sensitivity; this is the overriding first requirement, for after antibiotics are administered, the clinical picture may be confused, the patient no better, and the opportunity to make a precise diagnosis has been lost. However, it is unusual to have to treat wound infections with antibiotics. Only spreading infection or signs of systemic sepsis really justify them. Appropriate treatment must include drainage of pus and débridement if necessary.Presented with pus, or other material draining from a wound, the microbiologist can isolate the causative organisms and this may guide therapy. There are two approaches to treatment:
• the use of a narrow-spectrum antibiotic to treat a known sensitive infection, e.g. an MRSA sensitive to flucloxacibbin (or if not, vancomycin), isolated from pus;
• the use of broad-spectrum antibiotic combinations where the organism is not known or where it is suspected that there may be one, two or more, usually gut-derived bacteria responsible for the infection acting in synergy. Thus, during and following emergency surgery within the abdomen, or requiring the opening of bowel where any of the gut organisms may be responsible for subsequent peritoneal or bacteraemic infection, a combination of broad-spectrum penicillin, such as ampicillin or mezbociblin with an aminoglycoside, e.g. gentamicin, and metronidazole may be used postoperatively to support the patient’s own body defences.
Alternatives are a cephalosporin, e.g. cefuroxime, with metronidazole (increasingly popular as gentamicin toxicity and monitoring of bevels are avoided), or monotherapy using a carbapenem or quinolone.
In surgical units with multiple resistant Pseudomonas or other Gram-negative species (such as Klebsiella) which have become ‘resident opportunists’, there may become a need for a rotation of antipseudornonal and anti-Gram-negative chemotherapy between the broad-spectrum penicibbins, e.g. azbocilbin 2 g i.v. 8-hourly and cephabosporins, e.g. ceftazidime 50—100 mg/kg per day, or cefotaxime 2 g 8-hourly.
The use of these routines, the monitoring of subsequent wound infection and the alternation of combinations of chemotherapy should be monitored by the infection control team. It should not be forgotten, in treating postoperative pyrexial infection, that a failure to respond to a very broad spectrum of these combined antibiotics requires a critical bedside review to exclude collections of pus and other causes of a raised temperature.
New antibiotics should be used with caution and, wherever possible, sensitivities should have been obtained. There are certain general rules from which the choice of antibiotics may be based originally; thus it is unusual for Pseudomonas aeruginosa to be found as a primary infecting organism unless the patient has had surgical or hospital treatment. Local antibiotic sensitivity patterns vary from centre to centre and from country to country, and the sensitivity patterns of common pathogens will be known to the hospital microbiologist.
Antibiotics used in treatment and prophylaxis of wound infection
Antimicrobials may be produced by living organisms (antibiotics) or by synthetic methods. Some are bactericidal, e.g. penicillins and aminoglycosides, and others bacteriostatic, e.g. tetracycline and erythromycin. In general, penicillins act upon the cell wall and are most effective against bacteria that are multiplying and synthesising new cell wall materials. The aminoglycosides act at ribosomal bevel, preventing or distorting the production of proteins required to maintain the integrity of the enzymes in the bacterial cell.
Penicillin. Florey and Chain produced the first therapeutic preparation in 1941, benzylpenicillin, which has proved most effective against Gram-positive pathogens including most streptococci, the cbostridia and some of the staphylococci which do not produce j3-lactamase. It is still effective against actinomycosis, which rarely is a cause of wound infection, and may be used to treat spreading streptococcab infections specifically, even if other antibiotics are required as part of therapy of a mixed infection. All serious infections, e.g. gas gangrene, require high-dose intravenous benzylpenicilbin, e.g. 1.2 g 4-hourly.
Flucloxacillin and methicillin. These are beta-lactamaseresistant penicibbins and are therefore of use in treating staphybococcal 3-bactamase-producing organisms. This is the only reason for using them; and flucloxacillin has poor activity against other pathogens.
Ampicillin and amoxyciblin. These 3-bactam penicibbins are absorbed orally or may be given parenterabby. Pharmacodynamically, amoxycilbin is superior. Both are effective against enterobacteriaceae, against E. faecalis and the majority of group D streptococci, but not species of Klebsiella or Pseudomonas.
Mezlocillin and azlociblin. These are ureidopenicibbins with good activity against species of Enterobacter and Klebsiella. Azlocibbin is particularly effective against Pseudomonas. Each has some activity against Bacteroidesand enterococci, but
each is susceptible to 13-lactamase. Combined with an aminoglycoside, mezlocibbin is a valuable treatment for severe mixed infections, particularly Gram-negative organisms in the immunocompromised patient. Klebsiella strains are best treated with mezlocillin, Pseudomonas strains with azlocillin.
Clavulanic acid is available combined with amoxycibbin for oral treatment. This anti beta lactamase protects the amoxyciblin from inactivation by beta-bactamase-producing bacteria. It is of considerable value for treating Klebsiellastrains and beta-lactamase-producing E. coli infections, but of no value against Pseudomonas strains. Sometimes it is used for locabised cebbubitis or superficial staphylococcal infection and should be used for infected human and animal bites. It is available for oral or intravenous therapy.
Cephalosporins. There are many beta-lactamase-susceptible (not further considered here) and beta lactamase-stabbe cephalosporins available. There are three that find a place in surgical practice: cefuroxime, cefotaxime and ceftazidime. The first two are most effective in intra-abdominab skin and soft tissue infections, being active against S. aureus, and most enterobacteria. As a group, the enterococci (S. faecalis) are not sensitive to any of the cephalosporins. Ceftazidime, although being active against the Gram-negative organisms and, to a lesser extent, S. aureus, is most effective against P aeruginosa. These cephalosporins may be combined with an aminoglycoside, such as gentamicin, or an imidazole, such as metronidazole, if guaranteed anaerobic cover is needed.
Aminoglycosides. Gentamicin and tobramycin have similar activity and are particularly effective against the Gram-negative enterobacteriaceae. Gentamicin is effective against many strains of Pseudomonas, although resistance develops rapidly, but all aminogbycosides are inactive against anaerobes and streptococci. Serum levels immediately before and 1 hour after intramuscular injection must be taken 48 hours after the start of therapy, and dosage should be modified such that the trough level remains at or below 2.5 mg/litre and the peak level should not rise above 10 mg/litre. Ototoxicity and nephrotoxicity may follow sustained high toxic levels. They have a marked postantibiotic effect and single large doses are effective and may be safer.
Vancomycin is most active against Gram-positive bacteria. It is ototoxic and nephrotoxic. Serum bevels should be monitored but this antibiotic has proved most effective against mubtiresistant staphybococcal infection and, when given oralby, it is effective against C. difficile in cases of pseudomembranous colitis.
Metronidazole is the most widely used member of the imidazobe group and is active against all anaerobic bacteria. It is particularly safe and may be administered orally (up to 600 mg 8-hourly), rectally (up to 1 g suppository 8-hourly) or intravenously (500 mg 8-hourly). Infections with anaerobic cocci and strains of Bacteroidesand Clostridia are effectively treated — or prevented — by its use. Metronidazole is responsible for the reduction of anaerobic infections after abdominal, coborectab and pelvic surgery.
Mention has been made of meropenem which, together with imipenem, is a member of the carbopenems, which are stable to beta-lactamase. They have useful broad-spectrum anaerobic as webb as Gram-positive activity but are expensive.
The quinolones are potent microbicidab agents with action against Pseudomonas spp., e.g. ciprofloxacin. Their clinical robe in managing wound infection has not been defined.
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