Biapenem versus imipenem/cilastatin in the treatment of complicated intra-abdominal infections: report from a Swedish Study Group.

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.

Meropenem versus imipenem/cilastatin in the treatment of intra-abdominal infections.

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.

Effect of piperacillin/tazobactam treatment on human bowel microflora.

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.

Piperacillin-tazobactam versus imipenem-cilastatin for treatment of intra-abdominal infections.

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 (73 patients with appendicitis) participated in an open randomized comparative multicenter trial. A total of 40 men and 29 women (mean age, 53 years; age range, 18 to 92 years) were enrolled in the piperacillin-tazobactam group and 40 men and 25 women (mean age, 54 years; age range, 16 to 91 years) were enrolled in the imipenem-cilastatin group. The patients received either piperacillin (4 g) and tazobactam (500 mg) every 8 h or imipenem and cilastatin (500 mg each) every 8 h. Both regimens were given by intravenous infusion. A total of 113 patients were clinically evaluable. Of 55 patients who received piperacillin-tazobactam, 50 were clinically cured, while 40 of 58 patients in the imipenem-cilastatin group were clinically cured. The differences were significant (Wilcoxon test; P = 0.005). There were 4 failures or relapses in the piperacillin-tazobactam group and 18 failures or relapses in the imipenem-cilastatin group. The microorganisms isolated were eradicated in similar proportions in the two patient groups. Adverse reactions, mainly gastrointestinal disturbances and nausea, were noted in 13 patients who received piperacillin-tazobactam and in 14 patients who received imipenem-cilastatin. Results of the present study show that piperacillin-tazobactam is effective and safe for the treatment of intra-abdominal infections.

Effect of piperacillin/tazobactam therapy on intestinal microflora.

The effect of piperacillin/tazobactam treatment upon the intestinal microflora was studied in 20 patients with intraabdominal infections. The patients received piperacillin 4 g combined with tazobactam 500 mg q 8 h by intravenous injection for 4-8 days. Stool specimens were collected before, during and after therapy for cultivation of aerobic and anaerobic microorganisms. Six patients had measurable concentrations of piperacillin (1.2-276 mg/kg/faeces) and 4 patients tazobactam concentrations (0.8-22.2 mg/kg/faeces) in the faecal specimens during therapy. The number of enterobacteria and enterococci slightly decreased while there were no changes in the number of staphylococci and bacilli. The anaerobic microflora was also slightly affected. There was a minor decrease in the number of bifidobacteria, eubacteria, lactobacilli, clostridia and veillonella but the numbers of anaerobic Gram-positive cocci and bacteroides were not influenced by the treatment. After therapy, the aerobic and anaerobic microflora returned to normal levels in all patients. None of the patients had Clostridium difficile or cytotoxin in the stools or developed diarrhoea.

Identification of a dopamine- and 3'5'-cyclic adenosine monophosphate-regulated phosphoprotein of 32 kD (DARPP-32) in parathyroid hormone-producing cells of the human parathyroid gland.

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.

Etiological diagnosis of bacterial pneumonia by gram stain and quantitative culture of expectorates. Leukocytes or alveolar macrophages as indicators of sample representativity.

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.

Opsonizing antibodies against pneumococci detected by enhanced NBT. Reduction of phagocytizing granulocytes.

Specific opsonizing antibodies against pneumococci were demonstrated in serum by measuring their effect on the nitroblue tetrazolium (NBT) reduction of normal human granulocytes. In comparison to normal serum, convalescent sera from patients with severe pneumococcal disease caused a significant enhancement in NBT reduction in the presence of homologous antigen. Enhanced NBT reduction was observed in 24 of the 26 sera tested and was further increased by complement. The reaction was mainly type-specific, although a few cross-reactions did occur. A dose-response effect was observed when sera were tested in two-fold dilutions. The enhancement in NBT reduction could be partially eliminated by the absorption of sera with homologous antigens. The appearance and subsequent increase in opsonizing antibodies was observed in consecutive samples from one patient. This method can be useful in the study of immunological responses to pneumococcal vaccine or disease, since it measures antibodies which are essential for immune defence.

The influence of opsonization with specific antibody and complement on the nitroblue tetrazolium (NBT) reduction of neutrophil granulocytes. A methodological study and a clinical application.

The NBT reduction of granulocytes, increased in the presence of bacteria, was further enhanced bl specific antibody. The enhancement was dose-dependent and increased by complement. Clinically, the NBT test was used for measuring specific antibody in sera from patients after severe infections. With sera from 10 out of 14 patients with proven or suspected septicemia the NBT reduction was enhanced because of the presence of specific antibody. These results correlated well with the bacteriological findings and supported the view that the bacteria isolated from blood were relevant for the disease.

Compiled data on aminoglycoside, foremost netilmicin susceptibility of bacterial strains.

The MIC-values of 73 bacterial strains isolated in Malmö from patients treated with netilmicin have been determined by the agar dilution method for five aminoglycosides: amikacin, gentamicin, netilmicin, sisomicin and tobramycin. The results are compared with those obtained with the disc diffusion method in another Swedish investigation, comprising 202 strains and with results obtained in other places. Among the strains isolated in the two Swedish investigations, Escherichia coli strains were most prevalent, 28 and 77 respectively, and in this group no important differences could be found except for sisomicin. The importance of the inoculum size was investigated in a separate study on 24 strains of the Malmö material. These strains had also been tested one year earlier, using another size of the inoculum. The comparison showed that an inoculum less than 10(4) colony forming units resulted in lower MIC-values.

Mecillinam and ampicillin separately or combined in gram-negative septicemia.

Of 20 patients with gram-negative septicemia treated with mecillinam alone or in combination with ampicillin, successful therapeutic results were obtained in 16. In 11 patients treated with ampicillin alone, three failures responded successfully to a combination of mecillinam and ampicillin. Mecillinam MIC values of isolated Enterobacteriaceae were 0.05-0.4 micrograms/ml. In patients receiving 5 mg/kg mecillinam intravenously every six hours, the mean 0.5 hour concentration was 11.0 micrograms/ml and in those given 10 mg/kg 23.3 migcrograms/ml. No serious side effects were recorded. One patient on mecillinam developed an exanthema, as did three patients on combined therapy.

Cefamandole nafate: an evaluation of antibacterial activity, serum levels, clinical effect, and incidence of side reactions in 58 patients.

35 males and 23 females with skin and soft tissue infection, lower respiratory tract infection, urinary tract infection or septicemia with known etiology were treated with cefamandole nafate. The patients were to a large extent (30%) alcoholics and/or drug abusers. Cefamandole was given intravenously as 4 daily doses of 1 g in 52 cases and of 2 g in 6 cases for 8 to 16 (mean 10) days. The effect was considered to be good in 40 patients (70%). Adverse reactions, mostly slight and transient, were seen in 22 patients (38%). Peak serum levels varied from 26 to 82 (mean 50) micrograms/ml after 1 g doses and from 68 to 100 micrograms/ml after 2 g. Previous statements of a better in vitro activity of cefamandole than of older cephalosporins against some gram-negative bacilli were corroborated.

Netilmicin treatment of serious infections in patients with renal insufficiency.

Out of 24 patients with suspected moderate to severe infections and treated with the semisynthetic aminoglycoside netilmicin, 11 patients had decreased renal function. Non-bacterial aetiology was present in five cases. There was good netilmicin effect in 10 cases, indeterminate effect in 6 cases (due to simultaneously given other antibiotics) and failure in 3 cases. Pharmacokinetic parameters were studied. Curves are given for serum concentration patterns relative to creatinine clearance, and serum half-lives are calculated in renal dysfunction. In this series of very ill patients including impaired renal function, metilmicin proved to be an efficient antibiotic with low toxicity. Only one transient minor vestibular abnormality in an 80-year-old man with concomitant diuretic medication was registered.

The value of immunoelectroosmophoresis (IEOP) for etiological diagnosis of acute respiratory tract infections due to pneumococci and Mycoplasma pneumoniae.

Immunoelectroosmophoresis (IEOP) has been used to detect pneumococcal and Mycoplasma pneumoniae antigen in 324 sputum samples from 224 patients. Pneumococcal antigen was found in 30/37 samples from which pneumococci had earlier been isolated and in 72/243 specimens where they had not been found. Of these 72 samples 69 were from patients treated with antibiotics. Mycoplasma antigen was found in 9/57 sputum samples from which Mycoplasma had been isolated and in 2/32 other samples from patients with a serologically verified diagnosis of mycoplasmal infection. As to pneumococci, the IEOP is of value because of its rapidity and especially because antigen findings can be made in patients treated with antibiotics. In spite of sonication and concentration, mycoplasma antigen was too rarely found for the method, as now carried out, to be useful in diagnostic work.

Colonization and clinical superinfection with gram-negative bacilli in influenza.

Among 197 influenza A patients admitted to Roslagstull Hospital, abundant growth of gram-negative bacilli was found in 74 cases (38%). When assays for antibodies with the patients own strains as antigen were performed on paired sera with the indirect immunofluorescence technique, titre increases were obtained in 21 out of 55 patients (38%). In this last group signs of secondary infection, as secondary pneumonia, prolonged or recurring fever or late occurrence of leukocytosis and granulocytosis, were significantly more common than in patients without gram-negative findings. An analysis of possible interference by other bacteria did not invalidate the observations. Findings of gram-negative bacilli occurred most often in patients more than 50 years of age. The bacteria were probably hospital acquired in 32 out of 55 patients. Antibody responses took place both in the IgM and the IgG fraction.

Selective pressure of tetracyclines on the faecal flora. A comparison between tetracycline and doxycycline.

The aerobic faecal flora was studied in two groups of healthy adult persons, each group consisting of 18 individuals, before a course of either doxycycline or tetracycline HCI, at the cessation of therapy and 5 weeks afterwards. The main object of this study was to evaluate the effect of antibacterial treatment on the occurrence of mutagenic resistant and plasmid carried resistant strains in the faecal flora, and in particular development of resistant E. coli. The frequency of resistant strains increased after treatment with both of the drugs without significant differences.

Occurrence and significance of hemolytic streptococci groups b-u in human infectious disease.

245 strains of hemolytic streptococci, isolated from 225 patients with infectious diseasses, were grouped serologically according to Lancefield. About 40% belonged to group B and half of them were found in the genito-urinary tract. Another 40% belonged to the groups C and G, half of them being found in the respiratory tract and often as the only potentially pathogenic organism. About 10% of the isolates belonged to other of the groups E to T, including M streptococci, and were found under similar circumstances as the C and G isolates. The last 10% could not be referred to any of the groups A-U. In 4 cases group B streptococci were found as the only potentially pathogenic organism in typical erysipelas, and in 4 cases of septicemia the only bacterial finding from blood was a streptococcus of the groups B, C or G. In these cases, as in most others in which an etiological significance could be ascribed to steptococci of other groups than A, the patient was in a bad general condition, due to very high age, agranulocytosis, ethylism or narcomania.

The influence of bacterial superinfection on the clinical course of influenza. Studies from the influenza epidemics in Stockholm during the winters 1969-70 and 1971-72.

During two epidemics of influenza A infection in Stockholm 1969-72, 249 cases were selected for a study on the effect of bacterial superinfection. Bacterial involvement was demonstrated through cultures and serologic reactions. The occurrence of C-reactive protein in increased amount in serum was significantly more common in the group which had the strongest indication of bacterial infection. An increased duration of fever, and a higher incidence of pneumonia, leukocytosis and erythrocyte sedimentation rate over 50 mm/l h was also the rule in cases with bacterial involvement. During both epidemics the bacteria most often involved were pneumococci.