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May be used for staphylococcal infections but generally have been replaced by the newer cephalosporins.

All very similar. Effective against the common respiratory pathogens Streptococcus pneumoniae and Moraxelta catarrhalis but {excepting cefaclor) have poor activity against Hemophilus influenzae. Also active against Escherichia coli which, increasingly, is demonstrating resistance to amoxicillin and trimethoprim. May be used for uncomplicated upper and lower" respiratory tract, urinary tract and soft tissue infections, and also as follow-on treatment once parenteral drugs have brought an infection under control.

More resistant to [^-lactamases than the first-generation drugs and active against Staphylococcus aureus. Streptococcus pyogenes. Streptococcus pneumoniae. Neisseria spp.. Haemophilus influenzae and many Enterobaaeriaceae. Cefoxitin also kills Bactemrdes fragilii and is effective in abdominal and pelvic infections.

Cefuroxime may be given for community-acquired pneumonia,commonly due to Sircp pneumoniae (not when causal organism is Mycoplasma pneumoniae, Legionella or Ch/umydio).The oral form, cofuroximc oxetil, is also used for the range of infections listed for the first-generation oral cephalosporins (above)

More effective than the second-generation drugs against Gram-negative organisms whilst retaining useful activity against Gram-postivc bacteria. Cefotaxime, ceftizoxime and ceftriaxone are used for serious infections such as septicaemia, pneumonia, and for meningitis. Ceftriaxone also used for gonorrhoea and Lyme disease.

Active against a range of Gram-positive and Gram-negative organisms including Staphylococcus aureus (excepting ceiixime). Streptococcus pyogenes. Streptococcus pneumoniae, Neisseria spp.. Haemophilus influenzae and (excepting cefpodoxime) many Enterobaaeriaceae Used to treat urinary, upper" and lower respiratory tract infections.

bactericidal against most Gram-positive and Gramnegative aerobic and anaerobic pathogenic bacteria. They are resistant to hydrolysis by most p-lactamases. Only occasional pseudomonas relatives are naturally resistant, and acquired resistance is uncommon in all species.

Imipenem

Imipenem (tV21 h) is inactivated by metabolism in the kidney to products that are potentially toxic to renal tubules; combining imipenem with cilastatin (as Primaxin), a specific inhibitor of dihydropeptidase—the enzyme responsible for its renal metabolism—prevents both inactivation and toxicity.

Imipenem is used to treat septicaemia, particularly of renal origin, intra-abdominal infection and nosocomial pneumonia. In terms of imipenem, 1-2 g/d is given by i.v. infusion in 3-4 doses; reduced doses are recommended when renal function is impaired.

Adverse effects. It may cause gastrointestinal upset including nausea, blood disorders, allergic reactions, confusion and convulsions.

Meropenem (t'/2 1 h) is similar to imipenem but is stable to renal dihydropeptidase and can therefore be given without cilastatin. It penetrates into the CSF and is not associated with nausea or convulsions.

Vancomycin

Vancomycin (t'/2 8 h), a 'glycopeptide' or 'pepto-lide', acts on multiplying organisms by inhibiting cell wall formation at a site different from the (}-lactam antibacterials. It is bactericidal against most strains of Clostridia (including Clostridium difficile), almost all strains of Staphylococcus aureus (including those that produce ^-lactamase and methicillin-resistant strains), coagulase-negative staphylococci, viridans group streptococci and enterococci, i.e. several organisms that cause endocarditis.

Vancomycin is poorly absorbed from the gut and is given i.v. for systemic infections, as there is no satisfactory i.m. preparation. It distributes effectively into body tissues and is eliminated by the kidney.

Uses. Vancomycin is effective in cases of antibiotic-associated pseudomembranous colitis (caused by Clostridium difficile or, less commonly, staphylococci) in a dose of 125 mg 6-hourly by mouth (although oral metronidazole is preferred, being as effective and less costly). Combined with an aminoglycoside, it may be given i.v. for streptococcal endocarditis in patients who are allergic to benzyl-penicillin. It may also be used for serious infection with multiply-resistant staphylococci. Dosing is guided by plasma concentration monitoring.

Adverse effects. The main disadvantage to vancomycin is auditory damage. Tinnitus and deafness may improve if the drug is stopped. Nephrotoxicity and allergic reactions also occur. Rapid i.v. infusion may cause a maculopapular rash possibly due to histamine release (the 'red person' syndrome).

Teicoplanin is structurally related to vancomycin and is active against Gram-positive bacteria. The t'/2 of 50 h allows once daily i.v. or i.m. administration. It is used for serious infection with Grampositive bacteria including endocarditis, and for peritonitis in patients undergoing chronic ambulatory peritoneal dialysis. It is less likely to cause oto- or nephrotoxicity than vancomycin, but serum monitoring is required for severely ill patients and those with changing renal function to assure adequate serum concentrations are being achieved.

A rising prevalence of clinically-significant resistance and decrease in susceptibility to vancomycin and teicoplanin has become a serious worry recently with the emergence of vancomycin-resistant enterococci (VRE) or glycopeptide-resistant enterococci (GRE) and vancomycin-intermediate resistant Staphylococcus aureus (VISA or GISA). Only one naturally occurring strain of vancomycin resistant Staphylococcus aureus has been reported, but these will no doubt emerge in time and the appearance of antibiotics active against multiply resistant Grampositive bacteria, e.g. quinupristin-dalfopristin and linezolid (see p. 229), is welcome.

Cycloserine is used for drug-resistant tuberculosis (see p. 253).

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