Cephalosporins 3-lactamase susceptibility

In uncomplicated exacerbations, recommended therapy includes a mac-rolide (azithromycin, clarithromycin), second- or third-generation cephalosporin, or doxycycline. Trimethoprim-sulfamethoxazole should not be used because of increasing pneumococcal resistance. Amoxicillin and first-generation cephalosporins are not recommended because of /1-lactamase susceptibility. Erythromycin is not recommended because of insufficient activity against H. influenzae. 

E. Third-generation cephalosporins are susceptible to p-lactamase activity. 

RECEPTOR ANTAGONIST reported to have little sedative action, tazifylline hydrochloride tazifyUine. tazobactam (inn] (tazobactam sodium [usan]) is an ENZYME INHIBITOR active against the P-lactamase ( penicillinase ) enzymes produced by Gram-positive and -negative bacteria. Clinically, it can be used co-administered with -lactamase susceptible penicillins and cephalosporins, enhancing their antibacterial actions, tazobactam sodium tazobactam. 

Structural differences from penicillins render cephalosporins less susceptible to penicillinases produced by staphylococci, but many bacteria are resistant through the production of other beta-lactamases that can inactivate cephalosporins. Resistance can also result from decreases in membrane permeability to cephalosporins and from changes in PBPs. Methicillin-resistant staphylococci are also resistant to most cephalosporins. 

The antibacterial spectmm of moxalactam (Table 9) is similar in breadth and potency to that of cefotaxime (36). Hence, moxalactam (48) is classified with the third-generation cephalosporins. In general 1-oxacephalosporins are considerably more susceptible to P-lactamases than their sulfur counterparts... 

Approximately 30% to 40% of H. influenzae are ampicillin resistant. For this reason, many clinicians use a third-generation cephalosporin (cefotaxime or ceftriaxone) for initial antimicrobial therapy. Once bacterial susceptibilities are available, ampicillin may be used if the isolate proves ampicillin sensitive. Cefepime and fluoroquinolones are suitable alternatives regardless of /1-lactamase activity. 

First-generation cephalosporins, introduced into human medicine in the 1960 s and 1970 s, are basically similar in antibacterial activity and differ mainly in their pharmacokinetic properties. These include all of the currently available orally active cephalosporins, and are relatively susceptible to beta-lactamase, active against most Gram-positive bacteria and have a limited spectrum of activity against the Gram-negative organisms. 

It is broad spectrum cephalosporin with anti-pseudomonal activity. It is more susceptible to (3-lactamases and is primarily excreted in bile. Used in severe susceptible infections of respiratory, urinary, GIT, skin and soft tissues, meningitis, septicaemia, gonorrhoea, bacteremia and peritonitis. 

Core structures of four B-lactam antibiotic families. The ring marked in each structure is the -lactam ring. The penicillins are susceptible to bacterial metabolism and inactivation by amidases and lactamases at the points shown. Note that the carbapenems have a different stereochemical configuration in the lactam ring that apparently imparts resistance to lactamases. Substituents for the penicillin and cephalosporin families are shown in Figures 43-2 and 43-6, respectively. 

Both the cephalosporins and the penicillins owe their antibacterial action to their ability to block bacterial cell-wall biosynthesis. Cephalosporin C is less active than the penicillins, but is less susceptible to enzymatic destruction by /3-lactamases, which are enzymes that cleave the lactam ring. In fact, the so-called resistance of staph bacteria to penicillins is attributed to the propagation of strains that produce /3-lactamase. Numerous semisynthetic penicillins and cephalosporins have been made in the hope of finding new broad-spectrum antibiotics with high activity but with greater /3-lactam stability. Several of these are in clinical use. 

Conversion of the carboxyl groups in penicillins confers partial resistance to /3-lactamase (85-87). In cephalosporins, replacement of the acetyl group in position 3 of the dihydrothiazine ring [R in Fig. 1, (III)] by pyridine causes increased susceptibility to hydrolysis by /3-lactamases of Pseudomonas pyocyanea (31, 88), Enterobacter cloacae (45), E. coli (42, 88), and both the extracellular and cell-bound enzymes of B. cereus (38). 

Cephalosporins have been classified as first, second or third generation, largely on the basis of bacterial susceptibility patterns and resistance to p-lactamases (Figure 30.8). [Note They are ineffective against methicillin-resistant Staphylococcus aureus (MRSA), Listeria monocytogenes. Clostridium diffidle and the enterococci.]... 

The /3-lactam antibiotics may be susceptible to attack by three bacterial enzymes acylases, esterases and /3-lactamases. However, only the /8-lactamases play a significant role in the resistance of bacteria to penicillins and cephalosporins. 

Enzyme inhibitors such as cloxacillin and methicillin have been shown to potentiate the action of certain penicillins and cephalosporins against Ps. aeruginosa Figure 7.7). Thus, the presence of cloxacillin, which is a strong inhibitor of the inducible enzyme, potentiates the effect of cephaloridine which alone is susceptible to hydrolysis by the pseudomonas lactamase. Cloxacillin shows no antibacterial activity against... 

In cephalosporins susceptible to P-lactamases, opening of the [3-lactam ring occurs with concomitant loss of the substituent at R2 (except in cephalexin, where R2 represents H see Fig. 10.4). This is followed by fragmentation of the molecule. Provided that they are not inactivated by 3-lactamases, the cephalosporins generally have a broad spectrum of activity, although there may be a wide variation. Haemophilus influenzae, for example, is particularly susceptible to cefuroxime see also Table 10.2. 

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