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3. Probenecid should not be used with IV penicillin G. Probenecid is often used with oral penicillin preparations and with IM procaine or benzathine penicillin G to enhance serum levels by decreasing renal excretion. With IV penicillin, serum levels are easily adjusted by changing the dose, and probenecid is both unnecessary and dangerous. Probenecid predisposes patients to penicillin neurotoxicity by raising the CSF level and the serum level. This is the case because probenecid inhibits the active transport system that removes penicillin G from CSF after the drug has entered by passive diffusion. 4. Although it is possible to predict that some patients are more likely than others to have penicillin-susceptible strains, all patients with life-threatening disease should receive high-dose therapy until such susceptibility has […]

Continue reading " Penicillin Dosing for Pneumococcal Pneumonia: Conclusion "

The following recommendations apply to penicillin dosing as specific therapy for pneumococcal disease, as opposed to presumptive (empiric) therapy for pneumonia prior to the availability of blood culture results. We believe that pneumococcal pneumonia can sometimes be diagnosed with confidence on the basis of the history, physical examination, and sputum microscopy (Gram’s stain with or without use of the Quellung reaction). However, we also agree that initial presumptive therapy of pneumonia should usually be broad spectrum, as reflected by recent practice guidelines developed in the United States, Canada, and at least four European countries. The availability of rapid diagnostic tests for pneumonia, such as demonstration of pneumococcal antigen in urine, would allow physicians to use specific therapy more often.

Continue reading " Penicillin Dosing for Pneumococcal Pneumonia: Recommendations "

In the laboratory and in the clinical setting, two types of exposures to penicillin predispose to resistance. Prolonged exposures to nearly constant antibiotic concentrations at or near the MIC selects for resistant mutants with incrementally increased MIC values. These mutants exhibit penicillin-binding proteins with decreased affinity for the drug. Brief exposures to high (super-MIC) antibiotic concentrations followed by prolonged periods of subtherapeu-tic levels selects for a second type of resistant strains, called lysis-defective mutants. These mutants die slowly during penicillin therapy even though their MIC values are unchanged. Various studies indicate that the area under the time-serum concentration curve, not the kinetic pattern, is the important parameter for preventing the emergence of resistance with P-lactam antibiotics. canadian health & care mall

Continue reading " Penicillin Dosing for Pneumococcal Pneumonia: Relationship of Dose to Emergence of Resistance "

Shown in Figure 1 are the relationships between the MICs of penicillin G against S pneumoniae strains and representative penicillin serum levels after IV administration. What constitutes high-dose penicillin G therapy has never been rigorously defined. For instance, “an arbitrarily high dose” in one study consisted of 2.5 mu IV q6h. In 1992, Musher suggested that the optimal dose of IV penicillin is 500,000 U q4h. Pallares and colleagues recently suggested a dose of 150,000 to 200,000 U/kg/d, or 14 mu/d for a 70-kg adult patient. They noted that this would be effective for strains with MICs <4 μg/mL; whether strains with greater resistance (MIC >4  μ g/mL) will respond to that dose is not known. It should be noted that in much of the […]

Continue reading " Penicillin Dosing for Pneumococcal Pneumonia: High Dose vs Low Dose "

Four issues pertaining to IV penicillin G therapy will be considered: intermittent vs continuous infusion; high dose vs low dose; the relationship of dose to resistance; and cost. Intermittent vs Continuous Infusion The relative merits of intermittent vs continuous IV dosing of drugs with short serum half-lives such as penicillin G have been argued for many years without satisfactory resolution. Early advocates of intermittent dosing cited animal experiments showing that penicillin remained active against Gram-positive bacteria even after serum levels had become undetectable. Attributed to host defenses and/or residual activity of antibiotics, this “postantibiotic effect” gave theoretical rationale to twice-daily dosing with aqueous penicillin G despite the short serum half-life of penicillin given by this method.

Continue reading " Penicillin Dosing for Pneumococcal Pneumonia: Dosing Considerations "

Doses of penicillin used in the early 1940s were minuscule by today’s standards. The classic studies on the pharmacokinetics of penicillin G given IV were done with 20,000 to 40,000 Florey units. By 1945, a recommended regimen for severe pneumococcal pneumonia consisted of 25,000 U IV every 3 h (q3h) for two doses, then 10,000 U IM q3h for two doses. By 1946, it was noted that “sometimes the drip method is preferred to the intramuscular route by the scientific clinician but seldom is it preferred by the patient.” By the early 1960s, it was suggested that the “minimum curative dosage for [pneumococcal] pneumonia is less than 60,000 units daily, and a total daily dose of 600,000 units, as one injection of a depot preparation […]

Continue reading " Penicillin Dosing for Pneumococcal Pneumonia: Historical Overview "

Therapy of pneumococcal pneumonia is at a crossroads. Penicillin G, the drug of choice since 1942, is still recommended for specific therapy by most authorities. However, there is a widespread impression that penicillin G is seldom used for this purpose in most of the developed countries. Broader-spectrum antibiotics are favored for empiric initial therapy of community-acquired pneumonia because of the multiple potential etiologies and the lack of sensitivity, specificity, and cost benefit of the Gram’s stain and culture of sputum in nonintubated patients. Rising concerns about penicillin-resistant pneumococci often prompt therapy with newer cephalosporins or vancomycin for suspected or proved pneumococcal disease. However, invasive pneumococcal disease resistant to third-generation cephalosporins is now being reported. Moreover, wide use of both third-generation cephalosporins and also of vancomycin […]

Continue reading " Penicillin Dosing for Pneumococcal Pneumonia "