In order to compare the clinical and microbiological efficacies and safety of piperacillin plus tazobactam with those of imipenem plus cilastatin, 134 patients with intra-abdominal infections ( (11,14).Tazobactam is a newly developed P-lactamase inhibitor of the penicillanic acid sulfone class. Its structure is similar to that of sulbactam, except that one of the methyl groups of sulbactam is replaced by a triazolylmethyl group. It is more active than sulbactam against enterobacteria that produce class III and V plasmid-mediated 3-lactamases and is more active than clavulanic acid against those that produce class I chromosomal 3-lactamases (2,7,9).Piperacillin is an extended-spectrum penicillin which has been widely used in the treatment of serious infections. It is active against most enterobacteria and also shows good activity against enterococci and most anaerobic bacteria (5). * Corresponding author. t Scientific coordinators.Recently, the spread of 3-lactamase-producing organisms has raised concerns about the future utility of piperacillin and suggested that it should be used in combination with a 1-lactamase inhibitor such as tazobactam. In vitro studies have shown that piperacillin plus tazobactam is one of the most active penicillin-inhibitor combinations against a wide variety of resistant gram-negative aerobic and anaerobic bacteria (7,9

Sputum samples from 151 patients admitted to Roslagstull Hospital for Infectious Diseases, Stockholm, from Sept. 1978 through May 1979 with acute community-acquired lower respiratory tract disease and roentgenological evidence of acute pneumonia were examined by direct microscopy of gram-stained smears and semiquantitative culture. It was carefully noted if the specimen was collected before or after initiation of antibiotic therapy. For an estimate of the suitability of the samples for bacteriological examination 2 criteria were applied: (i) presence of alveolar macrophages, and (ii) purulence, i.e. a ratio leukocytes/squamous epithelial cells of greater than 5. The latter was found to be a good indicator of sample suitability, while the presence of macrophages was not. Of the 266 samples examined 76% were deemed purulent. Potentially pathogenic bacteria in numbers of greater than or equal to 10(5) colony forming units/ml were found in 67% of the purulent sputum samples obtained before antibiotic therapy but in only 36% if such treatment had already been started. Pneumococci were isolated from 52% of pre-treatment samples but from only 8% after treatment. H. influenzae was found as often in post-treatment samples (17%) as in pre-treatment ones (15%) and enteric gram-negative rods twice as often in post-treatment samples (11 vs. 6%). The use of gram-stained smears was a valuable aid in the interpretation of the culture results and the results could be made available to the clinician within minutes after receipt of the specimen. The results were in agreement with those of the cultures for about 75% of the purulent samples.

In order to compare the clinical and microbiological efficacy and safety of meropenem with imipenem/cilastatin, 249 patients with intra-abdominal infections participated in an open randomised comparative multicentre trial. Seventy-five men and 57 women (mean age 51 years) were enrolled in the meropenem group and 67 men and 50 women (mean age 52 years) in the imipenem/cilastatin group. The patients received either meropenem, 500 mg q 8 h, or imipenem/cilastatin, 500 mg/500 mg q 8 h by intravenous infusion for up to 17 days (mean 5 days). Ninety-seven of 99 patients (98%) receiving meropenem were clinically cured while 86 of 90 patients (96%) in the imipenem/cilastatin group were clinically cured. The microbiological response was satisfactory in 89 of 94 evaluable patients (95%) receiving meropenem and in 78 of 81 evaluable patients (96%) receiving imipenem/cilastatin. There was no significant difference in clinical and microbiological efficacy between the two treatment groups. Adverse reactions were noted in 26 patients receiving meropenem and in 36 patients receiving imipenem/cilastatin. The present study shows that meropenem is effective and well tolerated in the treatment of intra-abdominal infections.

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The effect of piperacillin/tazobactam treatment on the bowel microflora was studied in 20 patients with intra-abdominal infections. The patients were treated with piperacillin 4 g and tazobactam 500 mg administered intravenously every 8 h for four to eight days. Stool specimens were collected before, during and after treatment. Six patients had measurable faecal concentrations of piperacillin (1.2-276 mg/kg) and four patients measurable concentrations of tazobactam (0.8-22.2 mg/kg) during treatment. The mean numbers of enterobacteria, enterococci, bifidobacteria, eubacteria, lactobacilli, clostridia and Gram-positive cocci decreased while the numbers of anaerobic Gram-negative cocci and bacteroides were unaffected. The aerobic and anaerobic microflora returned to normal in all patients after the treatment had stopped.

118 patients with complicated intra-abdominal infections participated in an open randomized comparative multicenter trial in order to compare the clinical and microbiological efficacy and safety of biapenem with imipenem/cilastatin (Tienam). 31 men and 27 women (mean age 52.3 years) were enrolled in the biapenem group, and 43 men and 17 women (mean age 52.3 years) in the imipenem/cilastatin group. The patients received either biapenem 500 mg every 8 h or imipenem/cilastatin 500 mg/500 mg every 6 h by intravenous infusion for up to 13 days (mean 6.5 days). 28/43 evaluable patients (65.1%) receiving biapenem and 27/40 evaluable patients (67.5%) in the imipenem/cilastatin group were clinically cured. The microbiological response was satisfactory in 28/43 evaluable patients (65.1%) receiving biapenem and in 27/40 evaluable patients (67.5%) receiving imipenem/cilastatin. No significant differences in clinical or microbiological efficacy between the two treatment groups were found. The present study shows that biapenem may be useful in the treatment of intra-abdominal infections.

The cellular localization of DARPP-32, a dopamine- and cyclic AMP-regulated phosphoprotein of 32 kD, enriched in dopamine-innervated brain regions, was investigated in the human parathyroid gland using indirect immunofluorescence histochemistry. Monoclonal antibodies were used to demonstrate DARPP-32-like immunoreactivity (LI) in chief cells of the normal human parathyroid gland and in cells of human parathyroid adenoma. Direct double-labelling revealed coexistence of DARPP-32-LI with parathyroid hormone (PTH)-LI. It has previously been demonstrated that dopamine D1-receptors are present in the parathyroid gland and that dopamine and D1-agonists stimulate the release of PTH. The present results suggest that DARPP-32 may play a role in the cellular mechanisms leading to dopamine-induced PTH secretion.

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