Penicillinase-resistance

There are four groups of penicillins natural penicillins, penicillinase-resistant penicillins, aminopeni-cillins, and the extended-spectrum penicillins. See the... 

Because the natural penicillins have been used for many years, drug-resistant strains of microorganisms have developed, making the natural penicillins less effective than some of the newer antibiotics in treating a broad range of infections. Bacterial resistance has occurred within tire penicillins. Bacterial resistance is the ability of bacteria to produce substances that inactivate or destroy the penicillin. One example of bacterial resistance is tiie ability of certain bacteria to produce penicillinase, an enzyme that inactivates penicillin. The penicillinase-resistant penicillins were developed to combat this problem. 

It is important to determine (1) whether the isolate is methicillin-susceptible or methicillin-resistant and (2) whether the patient has a prosthetic valve. For patients with no prosthetic material, methicillin-susceptible staphylococci treatment should consist of a penicillinase-resistant penicillin (e.g., nafcillin or oxacillin) with or without gentamicin, and for methicillin-resistant strains, therapy should consist of vancomycin (see Table 71-4). Combination therapy with aminoglycosides, when used in these patients, typically is given only during the first 3 to 5 days of therapy. In the absence of prosthetic material, some treatment guidelines do not recommend combination therapy against MRSA. However, many clinicians may combine either gentamicin or rifampin with vancomycin if the patient is unresponsive to monotherapy. 

For staphylococcal PVE, treatment length increases significantly, typically requiring a minimum of 6 weeks (see Table 71-5). For MSSA, a penicillinase-resistant penicillin is still employed, as well as vancomycin for MRSA. However, with either regimen, the addition of both gentamicin for first 2 weeks and rifampin for the entire length of treatment is recommended. 

Spleen Aminoglycoside plus penicillinase-resistant penicillin Alternatives for penicillinase-resistant penicillin are first-generation cephalosporins or vancomycin... 

The answer is b. (Hardman, p 1077.) Unlike the other listed drugs, oxacillin is resistant to penicillinase. The other four agents are broad-spectrum penicillins, while oxacillin is generally specific for Gram-positive microorganisms Use of penicillinase-resistant penicillins should be resewed for infections caused by penicillinase-producing staphylococci... 

The answer is b. (Hardman, p 1077.) Oxacillin is classified as a penicillinase-resistant penicillin that is relatively acid-stable and, therefore, is useful for oral administration. Major adverse reactions include penicillin hypersensitivity and interstitial nephritis. With the exception of methi-cillin, which is 35% bound to serum proteins, all penicillinase-resistant penicillins are highly bound to plasma proteins. Oxacillin has a very narrow spectrum and is used primarily as an anti staphylococcal agent... 

BLIC, /5-lactamase inhibitor combination BL/BLI, jS-lactamase/jS-lactamase inhibitor FGC, first-generation cephalosporin MIC, minimal inhibitory concentration PRP, penicillinase-resistant penicillin SGC, second-generation cephalosporin TGC, third-generation cephalosporin. Penicillinase-resistant penicillin nafcillin or oxacillin. 

In a patient with a positive penicillin skin test or a history of immediate hypersensitivity to penicillin, vancomycin is the agent of choice. Vancomycin, however, kills S. aureus slowly and is generally regarded as inferior to penicillinase-resistant penicillins for MSSA. Penicillin-allergic patients who fail on vancomycin therapy should be considered for penicillin desensitization. 

Standard treatment for MSSA consists of 4 weeks of therapy with a penicillinase-resistant penicillin (see Table 37-6). 

Staphylococcus penicillinase-resistant penicillin or first-generation cephalosporin... 

Serious infections should be treated intravenously with a penicillinase-resistant penicillin (nafcillin) or first-generation cephalosporin (cefazolin). Patients with penicillin allergies should be treated with vancomycin or clindamycin. 

Penicillinase-resistant penicillins, first-generation cephalosporins, macrolides, and clindamycin should not be used for treatment because of their poor activity against Pasteurella multocida. 

A still broader spectrum (including Pseudomonas bacteria) is shown by car-boxypenicillins (carbenicillin, ticarcillin) and acylaminopenicillins (mezclocillin, azlocillin, piperacillin). These substances are neither acid stable nor penicillinase resistant. 

Penicillinase-resistant penicillins The percentage of staphylococcal isolates resistant to penicillin G outside the hospital is increasing, approximating the high percentage found in the hospital. Therefore, use a penicillinase-resistant penicillin as initial therapy for any suspected staphylococcal infection until culture and sensitivity results are known. 

Routes of Penicillinase-resistant Acid % administration stable Protein... 

Monitoring Obtain blood cultures, white blood cell, and differential cell counts prior to initiation of therapy and at least weekly during therapy with penicillinase-resistant penicillins. Measure AST and ALT during therapy to monitor for liver function abnormalities. 

Perform periodic urinalysis, BUN, and creatinine determinations during therapy with penicillinase-resistant penicillins, and consider dosage alterations if these values become elevated. 

Sexually transmitted diseases When treating gonococcal infections in which primary and secondary syphilis are suspected, perform proper diagnostic procedures, including darkfield examinations and monthly serological tests for at least 4 months. Resistance The number of strains of staphylococci resistant to penicillinase-resistant penicillins has been increasing widespread use of penicillinase-resistant penicillins may result in an increasing number of resistant staphylococcal strains. 

Nafcillin, oxacillin, cloxacillin, and dicloxacillin are more resistant to bacterial (3-lactamases than is penicillin G. Consequently, these antibiotics are effective against streptococci and most community-acquired penicillinase-producing staphylococci. Methicillin, which is no longer marketed in the United States, is another penicillinase-resistant antibiotic similar to nafcillin and oxacillin. For historical reasons, staphylococci resistant to oxacillin or nafcillin are labeled methicillin resistant. Many hospitals are reservoirs for MRSA and methi-cillin-resistant Staphylococcus epidermidis (MRSE). These nosocomial pathogens are resistant in vitro to all (3-lactam antibiotics. 

Chemical Class Penicillin derivative, penicillinase-resistant... 

Oral nafcillin absorption is erratic (consider alternate oral penicillinase-resistant penicillins)... 

Streptococcal infections Pharyngitis, rheumatic fever, otitis media and even for subacute bacterial endocarditis. Staphylococcal infections Penicillinase resistant penicillin can be used. Meningococcal infections Meningitis other infections caused by meningococci. 

Lactamase-positive Penicillinase-resistant penicillin9 As above... 

Acute Staphylococcus aureus Vancomycin + gentamicin Penicillinase-resistant penicillin1 + gentamicin... 

Cellulitis S aureus, group A streptococcus Penicillinase-resistant penicillin, cephalosporin (first-generation)2 Vancomycin, clindamycin, linezolid, daptomycin... 

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