Comparative in-vitro activity of sparfloxacin against genital pathogens.

The in-vitro activity of sparfloxacin against four pathogens commonly implicated in genital infections was compared with that of a number of other commonly administered antimicrobials. Sparfloxacin demonstrated excellent activity against Neisseria gonorrhoeae (MIC range of < or = 0.0002-5 mg/L for beta-lactamase producing strains, and < or = 0.0002-0.03 mg/L for non-beta-lactamase producing strains). This activity was similar to that of lomefloxacin and ciprofloxacin and was greater than that of ofloxacin. Sparfloxacin was more active against Ureaplasma urealyticum (MIC90 1 mg/L) than the other three quinolones (MIC90 4 mg/L). Sparfloxacin was much more active against Mycoplasma hominis (MIC90 0.06 mg/L) than the other quinolones (MIC90 1 mg/L). Sparfloxacin showed the most potent inhibitory and bactericidal activity of the quinolones against Chlamydia trachomatis with MIC and MBC of 0.06 mg/L (ofloxacin MIC and MBC 1 mg/L; ciprofloxacin and lomefloxacin MIC and MBC 2 mg/L). The results of this study and others performed by workers using different methods are consistently similar. Since sparfloxacin has broad activity against pathogens implicated in genital infections it may be a good therapeutic alternative for these syndromes.

Liver, spleen and kidney cultures in different conditions of splenic preservation.

The appearance of the postsplenectomy syndrome has made investigators focus all attention on the immunitary aspects that could change following a splenic extirpation. Besides this, bacterial clearance has been considered fundamental in this pathology. We present an experimental study comparing liver, spleen and kidney cultures in different conditions of splenic preservation, including autotransplantation, and with sepsis induced by the inoculation of capsulated Escherichia coli. The majority of tissue cultures were positive, showing, in must cases, a statistical correlation between the number of microorganisms in each organ for every animal. This confirms that all three organs act alike, as bacterial filters.

Penetration of cefuroxime and ceftazidime into human lungs.

We have studied the penetration of cefuroxime and ceftazidime into lung tissue of 40 patients subjected to pulmonary surgery. Samples of blood and lung tissue were taken 1 and 2 h after antibiotic administration. Patients were randomly assigned to four dosage schedule groups: group A received a single intravenous injection of 750 mg cefuroxime; the lung tissue levels at 1 and 2 h were 9.6 +/- 3.1 and 4.54 +/- 2.64 micrograms/g of cefuroxime; the percentage penetration from serum into the lung tissue was 33.7 and 34.6%, respectively. Group B patients received three doses of 750 mg cefuroxime; lung tissue levels were 17.1 +/- 7.7 and 14.7 +/- 5.4 micrograms/g, the percentage of penetration being 89.1 and 102.8% at 1 and 2 h. Group C received a single intravenous injection of 1 g ceftazidime; the lung tissue levels were 16.3 +/- 10.1 and 10 +/- 5.04 micrograms/g; the percentage of penetration from serum was 38.3 and 35.3%. Group D received three doses of 1 g ceftazidime; the lung tissue concentrations were 11.98 +/- 7.5 and 8.5 +/- 7.3 micrograms/g and the percentage of penetration 35.1 and 32.2% at 1 and 2 h after last dose.

Efficacy of ofloxacin (HOE 280) in a model of subcutaneous abscess: penetration and prevention of abscess formation.

A mouse model of subcutaneous abscess was used to determine the penetration into the abscess and the preventive value of ofloxacin (Hoe 280). Sterile cecal contents were injected subcutaneously combined with three different types of inoculum: Bacteroides fragilis, Escherichia coli and E. coli plus B. fragilis. For penetration studies three doses of 20 mg/kg of ofloxacin were administered intraperitoneally 8 hourly after abscesses had formed. Serum levels at 10, 20, 30, 60 and 90 min after the last dose showed mean values of: 6.9, 4.7, 3.8, 2.35 and 1.08 mg/l respectively. Simultaneously assessed ofloxacin abscess levels were 3.6, 4.1, 2.4, 1.91 and 1.98 mg/kg. In order to evaluate its preventive value, ofloxacin was given intraperitoneally at doses of 20 mg/kg in four regimens. Regimen A: one dose immediately before injection of the inoculum; regimen B: one dose 4 h after the injection of the inoculum; regimen C: one dose immediately before and two doses 8 h and 16 h after injection of the inoculum and regimen D: one dose 4 h, 12 h and 20 h after injection of the inoculum. The results are expressed as the percentage of the reduction in the number of abscesses formed in the survivors versus the control groups: regimens A) 30 to 70%; B) 0 to 40%; C) 50 to 60%, and D) 10 to 60%. The viable bacterial counts in the abscess contents were also assessed.

Comparative activity of imipenem (N-formimidoyl thienamycin) on enterococci and its interactions with aminoglycosides.

Activity of imipenem (N-formimidoyl thienamycin, ampicillin and vancomycin against 27 Streptococcus faecalis and 5 Str. faecium was determined. Also evaluated were the interactions of imipenem, ampicillin and vancomycin with streptomycin or amikacin or sissomicin. Imipenem showed the most inhibitory activity against Str. faecalis with MIC50 and MIC90 values 0.5 and 2 mg/l respectively, Str. faecium strains were less susceptible to imipenem with MIC50/MIC90 values of 2/16 mg/l. Imipenem showed good bactericidal activity against both groups of strains with MBC50/MBC90 values of 1/4 and 4/16 mg/l respectively. The most favourable interactions (synergy and addition) of imipenem were with streptomycin (72.2%) and sissomicin (53.2%). Combinations containing amikacin were the least favourable. Similar results were obtained with these combinations against Str. faecium.

Comparative concentrations of cefoxitin in human lungs and sera.

Eleven patients about to undergo pulmonary surgery received a bolus injection of 1 g of cefoxitin. The concentrations of cefoxitin in the serum 1 and 2 h after dosage were 38.5 +/- 1.89 and 23.7 +/- 2.56 mug/ml; the lung concentrations at the respective times were 12.6 +/- 0.7 and 10.06 +/- 0.43 mug/ml.

Meningitis due to beta-lactamase-producing Haemophilus influenzae: successful treatment with cefuroxime.

We have studied the clinical efficacy and pharmacokinetics of cefuroxime in 3 children aged 5, 7 and 10 months who were suffering from meningitis due to Haemophilus influenzae group b (beta-lactamase producers). The MICs of chloramphenicol against these three beta-lactamase-producing H. influenzae isolates were 8, 3.1 and 16 micrograms/ml, and those of cefuroxime were 0.25, 0.5 and 0.12 microgram/ml, respectively. The dosage of cefuroxime was 100 mg/kg/day divided in four 6-hourly intravenous doses for 15 days, and 10 mg given intrathecally every 48 h. Blood and spinal fluid levels were determined by microbiological assay. All the 3 children had excellent clinical and bacteriological responses with negative spinal fluid cultures after 48 h of treatment.

Clinical experience with cefotaxime (HR-756) in surgical patients.

Twenty adult surgical patients aged between 15 and 83 years (mean:45), 10 of whom had wound infections (one complicated with septicaemia), 2 with septicaemia, 1 with gynecological infection complicated with endocarditis, 5 with urinary tract infections and 2 with lower respiratory tract infections, were treated with parentally-administered cefotaxime. Aetiology was Proteus 7, E. coli 4, Pseudomonas 3, Enterobacter 2, Klebsiella 2 and 2 Serratia. Susceptibility testing was determined by the agar dilution method, with MIC values ranging from 0.01 to 5 microgram/ml, with two urinary isolates of Pseudomonas with MIC of 20 microgram/ml. Clinical responses were excellent in 13 (65 per cent) cases, moderate in 2 (10 per cent) and 3 (15 per cent) failed to respond to therapy. Clinical assessment was not possible in three patients. Bacteriological responses were excellent in 14 (70 per cent) cases, poor in 4 (20 per cent) and in two there was no follow-up. Systemic tolerance was good in all patients except one.

In vitro evaluation of new penicillins and cephalosporins upon P. aeruginosa and their interaction with mecillinam.

The in vitro activity of the new semisynthetic ureidopenicillins azlocillin (AZ) and mezlocillin (MZ), and of the new cephalosporin cefsulodin (CEF) were determined against 50 carbenicillin-sensitive (CARs) and 50 carbenicillin-resistant (CARr) P. aeruginosa clinical isolates. In the CARs group the most active antibiotics are AZ and CEF with MICs between 0.5 and 8 microgram/ml. Ticarcillin (TIC) and MZ showed more activity than CAR with MICs from 2 to 32 mu/ml. In this group there is a predominance of pyocine-type groups 1 and 3. In the CARr group, AZ is the most active antibiotic at low concentrations. At 64 microgram/ml of CEF, 72% of strains are inhibited as compared to 70% with AZ, 62% with MZ and 50% with TIC. In this group there is predominance of non-typeable strains. Interaction with mecillinam (MEC) and these antibiotics was studied on three different culture media (MH, NIH and DST). There were few cases of synergism with MEC and TIC combinations, mostly on DST medium. No appreciable synergism was found with other combinations of antibiotics.

Preliminary clinical trial with amikacin in chronic recurrent gram-negative bacterial infections refractory to other antimicrobial agents.

Eleven patients with 16 infections due to Enterobacteriaceae or Pseudomonas that were in most cases refractory to treatment with cephalosporins, kanamycin, gentamicin, tobramycin, carbenicillin, or ampicillin (administered singly or in combinations) received 1 g of amikacin daily by the intramuscular route (10 patients) or 0.4 g daily (one patient with renal insufficiency). The average duration of treatment was eight days. At the beginning of treatment, 18 pathogens were sensitive to amikacin at concentrations of 0.25-2 mug/ml. Of the 16 infections, 10 were cured clinically. Thirteen of the 19 pathogens isolated initially were eradicated, and five persisted during treatment but without change in in vitro sensitivity. A strain of Pseudomonas cepacia recovered from a diabetic patient and sensitive initially to 8 mug of amikacin/ml showed an eightfold increase in minimal inhibitory concentration. Superinfection with P. cepacia resistant to amikacin was noted in one case and urinary colonization with Candida albicans in another. No abnormalities of hematopoietic, hepatic, or renal function were observed in laboratory tests.

Susceptibility of current clinical isolates of Pseudomonas aeruginosa and enteric gram-negative bacilli to amikacin and other aminoglycoside antibiotics.

The susceptibility of current clinical isolates of Pseudomonas aeruginosa and Enterobacteriaceae to amikacin and other aminoglycosides was tested by a standardized disk sensitivity method. Minimal inhibitory concentrations (MICs) were determined for all 200 isolates tested, and mean MICs were calculated for each of 10 bacterial species. Amikacin proved to be the most effective of six aminoglycosides against nine bacterial species; isolates of Proteus morganii were slightly more sensitive to gentamicin than to amikacin. Whereas 50% of the 200 isolates could be considered resistant to gentamicin (MIC, greater than 16 mug/ml), 94.4% of the 126 enteric gram-negative bacilli and all 74 isolates of P. aeruginosa were sensitive to amikacin. At a concentration of 8 mug/ml, gentamicin inhibited 50% and tobramycin inhibited 67% of the 200 isolates. At 16 mug/ml, amikacin inhibited 96.5% of the 200 isolates; the respective figures for kanamycin, aminosidine, and streptomycin were 28.5%, 26.5%, and 24%. The virtual absence of cross-resistance between amikacin and gentamicin and between amikacin and the other four aminoglycosides was confirmed.