Antimicrobials penicillin

Fig. 11.7 Diagrammatic representation of MIC values obtained with two synergistic antimicrobials, penicillin and gentamicin. The resulting graph or isobologram (A) is obtained by linking MIC values for each drug alone and in various dilution combinations. The MIC values for penicillin and gentamicin alone are 1.0 mg/L and 32 mg/L, respectively. The slope of the isobologram for purely additive or antagonistic combinations is shown by B and C, respectively.

Antimicrobials Penicillins, erythromycin, tetracyclines Diarrhea, esophageal inflanunation... 

Widespread clinical acceptance continues to be accorded to the cephalosporins, and the field is extremely active as firms search for the ultimate contender. Among the characteristics desired is retention of the useful features of the older members (relatively broad spectrum, less antigenicity than the penicillins, relative insensitivity toward 3-lactamases, and convenience of administration) while adding better oral activity and broader antimicrobial activity (particularly potency against Pseudomonas, anaerobes, meningococci, cephalosporinase-carrying organisms, and the like). To a considerable extent these objectives have been met, but the price to the patient has been dramatically increased. 

The phenomenon of bacterial resistance to antibiotics was already known by the pioneers of the era of antibiotics, like Paul Ehrlich, who coined the term selective toxicity as the basic principle of antimicrobial therapeutics, as well as Gerhard Domagk, the inventor of the sulfonamide drugs, and Sir Alexander Fleming, the discoverer of the penicillins. When penicillin G was introduced into clinical practice in 1944, as many as 5% of the isolates of Staphylococcus aureus were resistant to penicillin, while 5 years later the percentage was 50%. 

As with all drugs, the specific side effects of the quinolones must be considered when they are chosen for treatment of bacterial infections [5]. Reactions of the gastrointestinal tract and the central neivous system are the most often observed adverse effects during therapy with quinolones. It should be underlined, however, that compared with many other antimicrobials, diarrhea is less frequently observed during quinolone treatment. Antibiotic-associated colitis has been observed rarely during quinolone therapy. Similarly, hypersensitivity reactions, as observed during therapy with penicillins and other (3-lactams, is less frequently caused by quinolones. Some other risks of quinolone therapy have been defined and must be considered if a drug from this class is chosen for treatment of bacterial infections. 

Amphotericin B, cephalosporins, penicillins, minocycline, nitrofurantoin, sulfonamide antimicrobials, and vancomycin... 

Allopurinol, barbiturates, carbamazepine, cephalosporins, cyclophosphamide, ethambutol, fluconazole, ibuprofen, lamotrigine, macrolides, nitrofurantoin, penicillins, phenytoin, propranolol, quinolones, sulfonamide antimicrobials, sulindac, tetracyclines, thiazides, valproic acid, and vancomycin... 

Allopurinol, barbiturates, benzodiazepines, captopril, carbamazepine, erythromycin, fluoroquinolones, isoniazid, NSAIDs, penicillins, phenothiazines, phenytoin, rifampin, sulfonamides antimicrobials, and tetracyclines... 

Albumin, aminophylline, aspirin, heparin, insulin, metoclopramide, NSAIDs, muromonab-CD3 (OKT3), opiates, penicillins, propafenone, quinidine, senna, sulfonamide antimicrobials, and vancomycin... 

The discovery of antimicrobials is among the greatest medical achievements of the twentieth century. Prior to the antimicrobial era, patients who contracted common infectious diseases developed significant morbidity or perished. The discovery of penicillin in 1927, followed by the subsequent discovery of other antimicrobials, contributed to a significant decline in infectious disease-related mortality during the next five decades. However, since 1980, infectious diseases related mortality in the United States have begun to increase, in part owing to increases in antimicrobial resistance. 

High-dose penicillin G traditionally has been the drug of choice for the treatment of pneumococcal meningitis. However, due to increases in pneumococcal resistance, the preferred empirical treatment now includes a third-generation cephalosporin in combination with vancomycin.13 All CSF isolates should be tested for penicillin and cephalosporin resistance by methods endorsed by the CLSI. Once in vitro sensitivity results are known, therapy may be tailored (Table 67-3). Patients with a history of type I penicillin allergy or cephalosporin allergy may be treated with vancomycin. Treatment should be continued for 10 to 14 days, after which no further maintenance therapy is required. Antimicrobial prophylaxis is not indicated for close contacts. 

Resistance to commonly prescribed antimicrobials such as the penicillins and macrolides/azalides increased dramatically in the late 1980s through the middle to late 1990s. Table 68-2 provides resistance information collected nationally from 1999 to 2004 using the Tracking Resistance in the US Today (TRUST) surveillance database.26 In 2004, the average national rate of resistance to penicillin and macrolides was approximately 18% and 25%, respectively. Susceptibility results alone do not account for clinical success or failures when treating pneumonia. 

Therefore, despite the 18% and 25% resistance to penicillin and macrolides, the clinical failure rate is less than this. Owing to the empirical treatment of CAP in the outpatient setting, establishing a meaningful clinical failure rate with any therapy is difficult to do. No studies have been performed that established a correlation between clinical failure rates with a particular antimicrobial agent and the percentage of resistant bacterial pathogens. 

If GAS is identified as the sole causative organism from deep tissue culture, antimicrobial therapy can be narrowed to high-dose IV penicillin G plus clindamycin. Antibiotic therapy should be continued until further operative debridements are unnecessary, the patient displays substantial clinical improvement, and fevers have abated for at least 48 to 72 hours.3... 

Newer antimicrobials have not demonstrated superiority in the prevention of SSI and should be reserved for treatment only. Carbapenems, antipseudomonal penicillins, and third-or fourth-generation cephalosporins are not appropriate antibiotics for surgical prophylaxis. Overuse of these antibiotics may contribute to collateral damage and the development of bacterial resistance. 

Verify the patient s allergy history and the type of reaction experienced. Attempt to discern between true allergy and adverse event. (3-Lactam-allergic patients may receive clindamycin, vancomycin, or other antimicrobials. Crossreactivity between penicillin allergy and cephalosporins is low but cephalosporins should be avoided in patients with a history of anaphylaxis to penicillins. 

Bjomeklett A, Midvedt T Influence of three antimicrobial agents - penicillin, metronidazole and doxycyclin - on the intestinal microflora of healthy humans. Scand J Gastroenterol 1988 94 928-932. 

Some combinations of antimicrobials are potentially antagonistic. For example, agents that are capable of inducing /1-lactamase production in bacteria (such as cefoxitin) may antagonize the effects of enzyme-labile drugs such as penicillins or imipenem. 

Serologic follow-up only recommended if antimicrobials otherthan penicillin are used... 

The role of antimicrobials for noninfected dog bite wounds remains controversial because only 20% of wounds become infected. Antibiotic recommendations for empiric treatment include a 3- to 5-day course of therapy. Amoxicillin-clavulanic acid is commonly recommended for oral outpatient therapy. Alternative agents include doxycycline, or the combination of penicillin VK and dicloxaciHin. 

Penicillin antibiotics must be used with caution because some strains of Bacillus anthracis possess an enzyme that inactivates penicillin. Other antimicrobial agents can be used as alternatives if the listed drugs are unavailable or in short supply. These include erythromycin, imipenem, clindamycin, vancomycin, and chloramphenicol.3... 

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