Therapy of penicillin-resistant pneumococcal meningitis.

Antimicrobial therapy of pneumococcal meningitis has been altered in recent years based on changes in pneumococcal susceptibility patterns, with emergence of strains that are either relatively or highly resistant to penicillin G (minimal inhibitory concentrations of 0.1-1.0 micrograms/ml and > or = 2 micrograms/ml, respectively. In areas of the world where relatively penicillin-resistant strains of Streptococcus pneumoniae are present, the third generation cephalosporins (either cefotaxime or ceftriaxone) should be used as empiric therapy, and for highly penicillin-resistant pneumococcal strains, vancomycin (with or without rifampin) is recommended. It is imperative that susceptibility testing be performed on all cerebrospinal fluid pneumococcal isolates to guide the choice of antimicrobial therapy. Vaccination recommendations with the 23-valent pneumococcal vaccine should also be strictly enforced for use in appropriate populations that are at increased risk of pneumococcal infections.

Pharmacokinetics of ciprofloxacin in subjects with varying degrees of renal function and undergoing hemodialysis or CAPD.

The pharmacokinetics of a single, oral dose of 750 mg of ciprofloxacin were studied in 35 subjects with various degrees of renal function (Group 1, Clcr > or = 80 ml/min; Group II, Clcr 50-79 ml/min; Group III, Clcr 10-49 ml/min) and on hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Blood, urine and CAPD dialysate samples were collected over a period of 48 hours after dosing. Data were fitted using non-linear, least squares regression. The mean Cmax was 3.4 +/- 1.0 mg/l and tmax was 2.3 +/- 0.9 hours. The mean AUC in Group I was 14.7 mg.h/l, Group II was 33.7 (p < 0.001), Group III 63.8 (p < 0.001), HD 57.9 (p < 0.0001) and CAPD 44.3 (p < 0.001). Half-life in Group I was 4.6 h, and was shorter than Group III (11.1 h, p < 0.001), HD (13.4 h, p < 0.001) and CAPD (8.9 h, p < 0.001). Total body clearance and renal clearance demonstrated significant differences also. The dialysis clearance in CAPD patients was 0.53 +/- 0.39 l/h. Peritoneal effluent concentrations varied from 0.6 mg/l during the first exchange, to a peak of 2.2 mg/l during the second, to 0.13 mg/l in the 48 hour (9th) exchange. Dosage adjustments of ciprofloxacin in the presence of renal insufficiency are indicated for subjects with a Clcr < 20 ml/min/1.73m2.

Potential neurologic toxicity related to ciprofloxacin.

A 74-year-old woman with multiple medical problems including chronic renal failure was admitted for treatment of a diabetic foot infection. On day 12 of therapy with oral ciprofloxacin and metronidazole, the patient experienced generalized myoclonus and muscle twitching. At that time it was realized that although the ciprofloxacin regimen prescribed was a usual dose for a skin and soft-tissue infection, it was excessive for her degree of renal function. This was thought to be the most likely cause of the patient's neurotoxicity. Seizure activity has been reported to occur with the quinolone antibiotics and, with the increasing use of these agents, dose reductions should be kept in mind to avoid potentially serious adverse reactions.

Clindamycin phosphate kinetics in subjects undergoing CAPD.

The kinetics of intraperitoneally administered clindamycin phosphate were studied in 9 volunteer subjects undergoing CAPD. Volunteers were assigned to 2 groups with the first group receiving clindamycin phosphate 300 mg/l in exchanges 1 through 5, and the second group receiving clindamycin phosphate 300 mg/l in exchange 1, and then 30 mg/l in exchanges 2 through 5. Clindamycin serum and dialysate effluent levels were determined by bioassay. When admixed with dialysate fluid and instilled into the peritoneal cavity, clindamycin phosphate is rapidly activated. Serum concentrations of clindamycin were rapidly achieved in both groups during the first exchange. Subjects in groups I and II had peak serum levels of active drug within 3 (3.94 ug/ml) and 5 (7.35 ug/ml) h, respectively. These results support the practice of not only administering intraperitoneal clindamycin phosphate to treat CAPD-related peritonitis, but using this route of administration to treat systemic infections due to susceptible bacteria in patients without intravenous access.