In patients with renal failure, penicillin in high doses can cause seizures. Nafcillin is associated with neutropenia and interstitial nephritis; oxacillin can cause hepatitis; and methicillin commonly caused interstitial nephritis (and is no longer used for this reason). Large doses of penicillins given orally may lead to gastrointestinal upset, particularly nausea, vomiting, and diarrhea. Ampicillin has been associated with pseudomembranous colitis. Secondary infections such as vaginal candidiasis may occur. Ampicillin and amoxicillin can be associated with skin rashes when prescribed in the setting of viral illnesses, particularly noted during acute Epstein-Barr virus infection, but the incidence of rash may be lower than originally reported. Piperacillin-tazobactam, when combined with vancomycin, has been associated with greater incidence of acute kidney injury compared to alternate β-lactam agents.
Cephalosporins are similar to penicillins but are more stable to many bacterial β-lactamases and, therefore, have a broader NN spectrum of activity. However, strains of E coli and Klebsiella sp Cefazolin most cephalosporins are a growing clinical concern. Cephalo-Cephalexin CH CH3 sporins are not active against L monocytogenes, and of the avail-NH2 able cephalosporins, only ceftaroline has some activity against Cefadroxil HO
CH CH3 enterococci. NH2
The nucleus of the cephalosporins, 7-aminocephalosporanic acid (Figure 43–6), bears a close resemblance to 6-aminopenicillanic NH2 acid (Figure 43–1). The intrinsic antimicrobial activity of HO
CH CH CH3 and R2 groups has yielded hundreds of potent compounds, many O CNH2 with low toxicity. Cephalosporins have traditionally been classi-
O natural cephalosporins is low, but the attachment of various R1 fied into four major groups or generations, depending mainly groups. Their unique characteristics and spectra of activity are outlined below.
on the spectrum of antimicrobial activity. Several cephalosporins developed more recently do not fit the traditional classification HOOC
First-generation cephalosporins include cefazolin, cefadroxil, cephalexin, cephalothin, cephapirin, and cephradine; cefazolin H2N N and cephalexin are the only two available in the USA. These drugs are very active against Gram-positive cocci, such as streptococci and staphylococci. Traditional cephalosporins are not active against methicillin-resistant strains of staphylococci; however, methicillin-resistant strains (see below). E coli, K pneumoniae, and
Proteus mirabilis are often sensitive to first-generation cephalo-H2N S N sporins, but activity against P aeruginosa, indole-positive Proteus CH3 species, Enterobacter sp, S marcescens, Citrobacter sp, and Acineto- bacter sp is poor. Anaerobic cocci (eg, peptococci, peptostrepto cocci) are usually sensitive, but Bacteroides fragilis is not.
A. Oral