A multicenter study of the prevalence and susceptibility patterns of isolates of Streptococcus pneumoniae with reduced susceptibility to penicillin G in Louisiana.

Because of increasing reports of multiple-antibiotic-resistant strains of Streptococcus pneumoniae and associated clinical failures, this study was performed to determine the prevalence of multiresistance among strains from nine Louisiana medical centers. Using a National Committee for Laboratory Standards broth microdilution method, 481 strains were tested. Of these, 70% were penicillin-susceptible (PS), 23% had intermediate minimum inhibitory concentration values to penicillin (I), and 7% were fully resistant to penicillin (PR). The isolation rates (15% to 40% for I strains and 0% to 33% for PR strains) at the various medical centers varied appreciably. The prevalence of penicillin resistance was highest among upper respiratory isolates, while cross-resistance to other antimicrobials varied. The least cross-resistance was noted among PS strains. However, strains with reduced penicillin susceptibility had high levels of cross-resistance. Among I strains, the prevalence of cross-resistance (%) was noted for amoxicillin/clavulanate (6%), cefuroxime (71%), cefaclor (91%), ceftriaxone (13%), cefotaxime (34%), erythromycin (67%), azithromycin (32%), and clarithromycin (32%). For PR strains, the prevalence of cross-resistance was 97% for amoxicillin/clavulanate, cefuroxime, and cefaclor; 67% for ceftriaxone and erythromycin; 89% for cefotaxime; and 69% for azithromycin and clarithromycin. These data emphasize the high prevalence of multiple-antimicrobial-resistance among strains of S pneumoniae with reduced penicillin susceptibility in this geographic area.

In vitro anaerobic data on ticarcillin/clavulanate. A review of an ongoing survey.

Although a number of new antimicrobial agents described as "broad spectrum" have been introduced during the past several years, it should be recognized that each of them has its own unique spectrum of activity, strengths and weaknesses that define its appropriate clinical use. This report reviews the comparative susceptibility data on 495 bacterial isolates obtained from obstetric and gynecologic patients and on 522 Bacteroides fragilis group isolates. Susceptibility testing was conducted with broth microdilution using twofold dilutions of antimicrobials. The overall minimal inhibitory concentrations-90 (MIC90) for the 495 isolates were very low, and few resistant isolates were found. The MIC90 for cefotetan was 16 times greater than that for ticarcillin/clavulanate and ampicillin/sulbactam. Cephalosporins showed good activity against anaerobic cocci but variable activity against anaerobic gram-negative rods. A relatively high percentage of B fragilis group isolates were also resistant to clindamycin. The addition of 2 mg/mL of clavulanate to ticarcillin caused a 4- to 32-fold decrease in the MIC90 for various Bacteroides species. Less than 2% of the strains tested were resistant to clavulanate plus ticarcillin or amoxicillin. These results suggest that monotherapy with such agents could replace combination antibiotic therapy for mixed obstetric and gynecologic infections.

Activities of ciprofloxacin and ofloxacin against rapidly growing mycobacteria with demonstration of acquired resistance following single-drug therapy.

The susceptibility to ciprofloxacin of 548 clinical isolates of rapidly growing mycobacteria belonging to eight subgroups or species was determined. The 170 isolates of Mycobacterium fortuitum biovar.fortuitum were most susceptible; the MIC for 90% of the organisms was 0.125 micrograms/ml. The other biovariants of M. fortuitum, M. smegmatis, and the M. chelonae-like organisms were less susceptible; the modal MIC was 0.5 micrograms/ml, and the MIC for 90% of organisms was 1.0 micrograms/ml. The two subspecies of M. chelonae were generally resistant, with only 8% of 206 isolates falling in the moderately susceptible category (MIC, 2 micrograms/ml) and only 2% falling in the susceptible category (MIC, less than or equal to 1 micrograms/ml). MICs of ofloxacin averaged 1 to 2 dilutions higher than those of ciprofloxacin for all subgroups tested. Three patients with M. fortuitum cutaneous disease relapsed after an initial response to therapy with ciprofloxacin, and their isolate was shown to have acquired drug resistance. Mutational frequencies for M. fortuitum with ciprofloxacin were relatively high (10(-5) to 10(-7), and MICs for single-step mutants were similar to those for the clinically resistant strains. Thus, despite the excellent activity of ciprofloxacin against rapidly growing mycobacterial groups other than M. chelonae, single-drug therapy should be used with caution because of the risk of development of mutational resistance.

Comparative clinical trial of imipenem-cilastatin (N-formimidoyl-thienamycin-dehydropeptidase inhibitor) and cefazolin.

One hundred and eighty-six patients were randomized to receive either imipenem-cilastatin (94 patients) or cefazolin (92 patients). Imipenem-cilastatin (250 mg 6 hourly iv) or cefazolin (1000 mg 6 hourly iv) were given for 5 to 14 days. An assessment of efficacy could be made in 141 patients, 72 of whom received imipenem-cilastatin and 69 of whom received cefazolin. Reasons for exclusion included failure to isolate a causative organism (20 patients), less than 5 days of treatment (16 patients), inadequate follow up or culture (5 patients), concomitant administration of another antibiotic (1 patient), and resistance to the study drug (3 patients, all of whom were in the cefazolin group). No isolates resistant to imipenem were found. Sites of infection included skin and soft tissue (91 patients), lower respiratory tract (21 patients), urinary tract (16 patients), bone and joint (8 patients), primary bacteraemia (4 patients) and miscellaneous other sites (1 patient). Bacteria isolated included Staphylococcus aureus (65 patients), group A streptococcus (42 patients), Escherichia coli (17 patients), other Gram-negative bacilli (37 patients), anaerobic bacteria (34 patients) and other bacteria. Imipenem was more active than cephalothin in vitro against pathogenic bacteria isolated from evaluable patients. Cure or improvement was seen in 68 of the 72 imipenem-cilastatin patients (94%) and in 68 of the 69 cefazolin patients (99%). Relatively few abnormal laboratory tests and adverse experiences were noted, and there were no differences in this between the two treatment groups. We concluded that imipenem-cilastatin is safe at the dose used. It is as effective as cefazolin in mild to moderate infections caused by common pathogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Piperacillin v Carbenicillin in the therapy for serious infections.

One hundred seven patients were treated with either piperacillin (56) or carbenicillin (51) in an open randomized trial of hospitalized patients with pleuropulmonary (40), urinary tract (26), gynecologic (21), skin and soft-tissue (eight), joint (five), bone (three), and miscellaneous other infections (four). Patients with urinary tract infections were given 150 mg/kg/day of piperacillin sodium or 200 mg/kg/day or carbenicillin sodium in divided doses every six hours intravenously. Patients with other infections were given 250 mg/kg/day of piperacillin sodium and 450 mg/kg/day of carbenicillin sodium; 53/56 (95%) patients treated with piperacillin and 45/51 (88%) patients treated with carbenicillin were cured clinically. In general, the drugs were well tolerated. There were, however, more adverse experiences in the groups taking carbenicillin. Of special interest was the finding of liver function test abnormalities in 17/78 (21%) carbenicillin recipients (evaluative and nonevaluative cases). We concluded that piperacillin was effective and safe. It has potential for use in a great variety of infections.

Moxalactam in the therapy of serious infections.

Sixty-seven patients were treated with moxalactam in a noncomparative trial of hospitalized patients; 32 had endometritis or chorioamnionitis, 12 had skin and soft tissue infections, 5 had osteomyelitis, 5 had pneumonia, 5 had urinary tract infections, 4 had arthritis, 2 had sepsis from an unknown source, 1 had endocarditis, and 1 had peritonitis. Bacteremia was present in 12 of these patients. Patients were given 3 to 12 g of moxalactam per day (mean, 6.24 g/day) in divided doses every 6 to 8 h. Seven patients were given intramuscular treatment for 3 to 20 days for part or all of their therapy. The rest were given intravenous treatment exclusively. Treatment was continued for 2 to 42 days (mean, 10 days). The dose and the duration of therapy were determined by the type of infection and the response of each patient. There were four treatment failures and one enterococcal-clostridial superinfection. Moxalactam was well tolerated. Allergic reactions led to the discontinuation of the antibiotic in three patients. Prolonged prothrombin and partial thromboplastin times were observed in 2 of 11 patients tested; in both instances in patients had severe underlying diseases, including malnutrition and alcoholism. Pain on intramuscular injection was noted in two patients receiving 1,500 mg, but not in five receiving a lower dose; in one case the pain forced the use of intravenous therapy after one dose, and in the other case the pain was mild and the patient was treated for 20 days. We concluded that moxalactam was effective in the treatment of the types of infections included in this study and produced few adverse reactions.

Cefamandole therapy in anaerobic infections.

Thirty-one adult patients with infections due to anaerobic bacteria were treated with cefamandole. Bacteroides fragilis group (17) and Bacteroides melaninogenicus (13) were the most frequent anaerobes isolated. Duration of therapy varied from 2 to 49 days. Results were judged satisfactory in 26 cases, and unsatisfactory in 1 case. Four cases could not be evaluated. Adverse reactions occurred in 16 patients and included positive direct Coombs' test without hemolysis, transient liver function abnormalities, phlebitis, reversible neutropenia, fever, eosinophilia, and toxic epidermal necrolysis. The more significant reactions were associated with prolonged therapy. None was lethal. These data suggest that cefamandole is effective in treatment of most anaerobic infections.