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Gram-negative bacilli were exposed to the action of mecillinam in urine and the mechanism of resistance in regrowing strains was studied. It was found that active drug destruction occurred with some strains, with others slow growing resistant isolates were found. Strains of Proteus mirabilis and Klebsiella spp. were found to be resistant by drug destruction due to increasing alkalinity of the urine.Thirty-eight hospital inpatients with urinary tract infections were treated with 400 mg of pivmecillinam 4 times a day for 5 to 7 days. Of the 35 patients who were adequately followed up 29 were classified as a cure. Side effects were minimal. [ABSTRACT FROM PUBLISHER]

Mecillinam is a novel β-lactam antibiotic with a wide range of activity against Gramnegative bacteria. The effect of alteration of pH, inoculum size and presence of serum upon the minimum inhibitory and bactericidal concentration of mecillinam was investigated. The stability of the drug in human serum over 24 h at 37°C was investigated and the relationship of β-lactamase production by various bacteria upon the activity of the compound was noted. [ABSTRACT FROM PUBLISHER]

The ultra long-acting sulphonamide sulfametopyrazine was used as treatment for bacteriuria in pregnancy. In an initial trial a single dose of 2 g was given producing a cure-rate of 68%. In a randomized comparative trial this dose (cure-rate 67%) was compared with conventional treatment with sulphadimidine (cure-rate 50%, and with 2 similar doses given at an interval of 4 days (cure-rate 73%, The volunteer pharmacological studies which lead to development of this last dosage regime are described, as is the effect of urinary alkalization on pharmacology. Side effects with sulfametopyrazine occurred only infrequently and were considerably fewer than in patients taking sulphadimidine. [ABSTRACT FROM PUBLISHER]

The effect of altering the site of injection between the thigh and buttock upon the serum and urinary levels of cephacetrile, cephaloridine and gentamicin was investigated. The peak serum levels of cephacetrile were considerably higher after a thigh injection than a buttock injection. A similar study with gentamicin showed the same trend, but the differences were not significantly different. Serum levels of cephaloridine showed no significant differences, but the urinary recovery of the drug was greater after a thigh injectionThe effect of taking oral contraceptives and the serum levels of cephaloridine attained after intramuscular dosing was investigated. It was noted that females who were on oral contraceptives had lower serum levels of cephalondine than the week they were not taking this medication [ABSTRACT FROM PUBLISHER]

The increasing use of the aminoglycoside antibiotic gentamicin together with an awareness of the importance of adequate serum levels for therapy and of a possible relationship between those levels and its main side effect, ototoxicity, has led to many laboratories being asked to perform gentamicin serum assays. The relatively low therapeutic ratio of the aminoglycosides antibiotics indicated that accurate assays were essential if they were to realize their full potential in controlling therapy. With this in mind four laboratories, our own among them, exchanged some specimens of sera containing gentamicin in late 1971 and early 1972. The results showed wide divergencies in the estimated concentration of single samples by the participant laboratories. This was clearly a worrying state of affairs and recognizing this, the British Society for Antimicrobial Chemotherapy (B.S.A.C.) sponsored a number of larger surveys. In 1973 this laboratory was invited by the Public Health Laboratory Service (P.H.L.S.) Quality Control Committee to send out specimens for antibiotic assay. The experiences described here are those of the later B.S.A.C. surveys and those under the joint auspices of the P.H.L.S. and B.S.A.C. in 1973 and 1974: For convenience of reference the surveys are designated as follows: January 1973 (B.S.A.C.) —Survey A March 1973 (B.S.A.C.) —Survey B June 1973 (P.H.L.S./B.S.A.C.) —Survey C (P.H.L.S. 20th Distribution) February 1974 (P.H.L.S./B.S.A.C.)—Survey D (P.H.L.S. 28th Distribution) Gentamicin was chosen as the antibiotic to be investigated for the reasons given above. Furthermore, it was found to be by far the most frequently assayed antibiotic in a small poll taken among participant laboratories, and it seemed to be a technically suitable drug because of its stability in solution at room temperature. [ABSTRACT FROM PUBLISHER]

The use of high-voltage electrophoresis and bioautography for the separation mixtures of antibiotics received in clinical serum samples is described. The electrophoretic characteristics of 39 antibiotics are given as is the accuracy of the method for quantitating three antibiotics. In screening 189 consecutive serum samples submitted for routine antibiotic assay, undisclosed antibiotics were revealed by the technique in 35. [ABSTRACT FROM PUBLISHER]

The adenylytransferase/acetyltransferase methods of gentamicin assay have been evaluated for accuracy, speed, and cost. For a comparable cost of materials the latter method is more accurate than that using the adenylytransferase enzyme. The acetyltransferase method is much quicker than the adenyltransferase due to the shorter time necessary for radioactive counting. Sonication is an easier method of enzyme preparation than the previously used osmotic shock technique. The acetyltransferase method is reproducible and there was a very good correlation between it and a microbiological agar-plate diffusion method. [ABSTRACT FROM PUBLISHER]

The majority of clinical microbiology laboratories in the UK use comparative disc diffusion methods based on the Stokes' method to determine antibiotic susceptibility. The technical validity of the results obtained from the modified Stokes' method of disc testing and how they relate to MIC data are not known. We studied susceptibility testing using a modified Stokes' disc diffusion method for a wide range of clinical isolates against which MICs had been determined by collaborators not involved with the disc testing evaluation. Results indicated that for 1301 organism-antibiotic combinations the number of major errors (where resistant strains were reported as sensitive) was 21/468 (4.4%) and the number of minor errors (where sensitive strains were reported as resistant) was 14/713 (1.9%) using ciprofloxacin breakpoints of 0.5 and 2 mg/L. There was good correlation between the disc susceptibility test and the MIC for 119 isolates of Enterobacteriaceae tested with the exception of Serratia spp. Excluding Serratia spp. the number of major errors for Enterobacteriaceae was 1/200 (0.5%). Data revealed 2/25 (8%) major errors for Pseudomonas aeruginosa and 1/45 (2.2%) for Acinetobacter spp. Haemophilus influenzae showed a number of unexpected categorization errors. The modified Stokes' method performed accurately for Staphylococcus aureus and coagulase-negative staphylococci when tested for susceptibility to gentamicin, erythromycin, teicoplanin and vancomycin. No major errors were reported for Streptococcus pneumoniae and beta-haemolytic streptococci. Problems occurred with the detection of antibiotic resistance in Enterococcus spp. Major errors were seen for ampicillin (2/12 strains), teicoplanin (5/6 strains) and vancomycin (5/13 strains) using a 30 microg disc but only 1/13 strains using a 5 microg disc. Overall, from our data, the modified Stokes' disc diffusion antibiotic susceptibility test showed an unacceptable number of major errors but an acceptable number of minor errors. [ABSTRACT FROM AUTHOR]

In order to compare the prevalence of antibiotic resistance in different geographical areas, it is necessary to ensure agreement between laboratories on the assignment of strains to 'susceptible' and 'resistant' categories. An international quality assessment was performed to investigate the performance of susceptibility testing of Klebsiella spp. Ninety-five strains of klebsiellae were selected from clinical isolates at the London Hospital Medical College (LHMC). These included strains with a diversity of susceptibility profiles to amoxycillin/clavulanate, piperacillin, ceftazidime, cefuroxime, ciprofloxacin, gentamicin and trimethoprim. The strains were sent to 13 participating laboratories in Europe and the USA and laboratories were asked to test the susceptibility of these strains to these antibiotics by their usual methods. They were also asked to provide details of the method used to test susceptibility. Several different standard recommended testing methods were used. Reporting of susceptibilities was generally accurate, but a number of anomalies were noted. Discrepancies of reporting between the LHMC and the participating laboratories was more marked for resistant strains, particularly in the detection of resistance to cefuroxime and ciprofloxacin, as well as the assignment of susceptibility and resistance to piperacillin and amoxycillin/clavulanate. Some discrepancies could be attributed to the use of different breakpoints, leading to differing assignment of susceptibility. Methodological variations including disc content, inoculum and failure to measure and interpret zone sizes consistently also led to anomalies. This quality assessment programme has helped to identify problems in susceptibility testing which should be investigated further. [ABSTRACT FROM AUTHOR]

Serum concentrations of ciprofloxacin were reviewed in 22 patients given ciprofloxacin 400 mg intravenously 12 hourly for severe infection. No dosage modifications were made in patients with renal impairment. Patients who had either bowel or liver pathology in addition to renal failure had significantly higher serum concentrations than all other patients. Dosage reduction of ciprofloxacin in patients with severe sepsis and impaired renal function is not required unless they have co-existent intra-abdominal disease. [ABSTRACT FROM AUTHOR]

Twelve patients undergoing total hip anthroplasty received, at the induction of anaesthesia, cephamandole (1 g) and cefuroxime (1.5 g); further doses of cephamandole (1 g) and cefuroxime (750 mg) were given at 8 and 16 h after the operation. Routine total hip arthroplasty was performed and at timed intervals during operation samples of bone, fat and blood were collected for assay for HPLC analysis. Samples of the haematoma fluid that formed around the operation site and further blood samples were also collected at 7 and 15 h after the operation. Although considerable variation was observed in the bone and fat concentrations of both agents, the cefuroxime levels were substantially higher than those of cephamandole, with mean values for bone of cefuroxime 36.0 mg/L (95% CI 29.0-43.0 mg/L) and cephamandole 18.3 mg/L (95% CI 14.2-22.4 mg/L) and for fat of cefuroxime 15.0 mg/L (95% CI 11.1-18.9 mg/L) and cephamandole 11.2 mg/L (95% CI 7.2-15.2 mg/L). When corrected for blood concentrations the penetration of both agents was similar (bone, 43.6% cefuroxime and 37.8% cephamandole; fat, 16.0% cefuroxime and 19.2% cephamandole). Cefuroxime concentrations in haematoma drain fluid were higher than those of cephamandole 6-8 h after the operation (17.8 versus 8.3 mg/L) but lower at 14-16 h (7.7 versus 9.6 mg/L). We conclude that there are no significant differences between the bone, fat or haematoma penetration of cefuroxime and cephamandole and that any differences in the absolute levels of the two agents are due to differences in the total drug administered rather than their ability to penetrate into these sites. Time-kill curves for cefuroxime and cephamandole against five clinical isolates of Staphylococcus aureus failed to identify any significant differences between the rates of kill for the two agents at the concentrations seen in bone, fat or haematoma fluid. For both prophylaxis regimens antibiotic concentrations exceeded the MICs for potential pathogens for the duration of the operation and also in the haematoma which surrounds the operation site for up to 24 h after the operation. [ABSTRACT FROM AUTHOR]

We conducted a prospective observational study on the medical management and health service resource utilization associated with the hospital care of patients with community-acquired lower respiratory tract infection. Between January 1994 and June 1995, 28 such patients developed Clostridium difficile-associated diarrhoea; these 28 patients were matched with 56 age-matched patients, who were used as a control group in a comparative study. Progress during the first week after admission was similar as measured by fever days and pathology or radiology use. The use of iv cephalosporins (g/day) during the first week was greater in the group who developed C. difficile-associated diarrhoea than in controls. The length of hospital stay was 36.4 +/- 21.6 days in patients with C. difficile-associated diarrhoea compared with 19.8 +/- 13.3 days in controls. Cases also required more pathological and radiological tests and greater use of antimicrobials and other drugs; however, if pathology and radiology use was calculated per day of patient stay there was no difference between the two groups. When antimicrobial use was compared, controlling for the time taken until found to be C. difficile toxin positive, patients with C. difficile infection received more iv cefuroxime as well as more total cephalosporins, beta-lactams and macrolides measured in g/day. Interestingly, in this study we could not show an increased mortality associated with C. difficile diarrhoea despite obvious evidence of morbidity. The development of C. difficile-associated diarrhoea substantially increases health care resource utilization for individual patients who are admitted to hospital with lower respiratory tract infection. [ABSTRACT FROM AUTHOR]

There is a feeling that the contribution of researchers from the United Kingdom in the antimicrobial chemotherapy area is in decline, and we, therefore, reviewed publications in the Journal of Antimicrobial Chemotherapy (JAC) and Antimicrobial Agents and Chemotherapy (AAC) in 4 of the last 14 years. In absolute numbers the total number of UK first author publications in these two journals were 103, 78, 107 and 82 in 1980, 1985, 1990 and 1994 respectively. The percentage of first author papers from the UK in JAC was 35%, 21%, 24%, 23% and in AAC was 5.7%, 4.9%, 5.1% and 4.7% for the years 1980, 1985, 1990 and 1994 respectively. Within the UK there has been a relative decline in the number of publications produced by NHS hospital departments and an increase in those produced by universities. Ten institutions (four universities, two pharmaceutical companies and four NHS departments) produced almost half of the UK publications. There is no room for complacency about the state of British antimicrobial research and the relative decline in the NHS hospital sector's contribution, the largest contributor numerically, even before the full impact of the ongoing NHS reforms, is cause for concern. [ABSTRACT FROM AUTHOR]

The effect of increasing meropenem concentrations up to 250 mg/L, as might occur if 3 g was given as a single daily intravenous dose, was investigated in terms of bactericidal activity, post antibiotic effect (PAE) and modified controlled effective regrowth time (mCERT). Increasing the meropenem concentration above 50 mg/L did not result in increased bacterial killing, while concentrations over 75 mg/L did not result in longer PAE or mCERT. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of once a day netilmicin (6 mg/kg) was studied in 21 neonates. The babies were divided into three groups according to gestational age: group I aged > 36 weeks; group II between 34-36 weeks and group III < 34 weeks. Serum concentrations were variable between patients and the concentration 24 h after the first dose ranged from 0.8 to 3.8 mg/L with only two babies having concentrations of < 1 mg/L while seven had concentrations of > 2 mg/L. There were also large patient-to-patient variations in serum half-life, volume of distribution, area under the curve and relative plasma clearance such that these parameters could not be correlated to gestational age or weight. Absolute plasma clearance was correlated with both gestational age and weight. There was evidence of accumulation between the first and second dose for all three patient groups and for patients of gestational age < 34 weeks (group III) these observations were statistically significant. A netilmicin dosage of 4.5 mg/kg once a day may be more suitable for all neonates supported by assay of serum concentrations. [ABSTRACT FROM AUTHOR]

A time-kill curve employing nine sampling times over 6 h was used to provide data which were then used to develop a theoretical (best-fit) curve. From the theoretical curve parameters describing the rate of kill (α), time from addition of antibiotic to initiation of killing (d) and a function of the degree of killing observed (Ym/ Yo) were defined. The area-under-the-curve (AUC) was calculated from the theoretical curve. The variability of each parameter was assessed using a theoretical curve to fit the data from experiments done on three occasions and in triplicate. In terms of the parameters α, d, Ym/Yo and AUC, no synergy was demonstrated with combinations of piperacillin/tazobactam plus ciprofloxacin or gentamicin when compared with single antibiotics. The AUC represents the best summary parameter of a time-kill curve but should be supported by other parameters describing the best-fit curve. [ABSTRACT FROM PUBLISHER]

The agar dilution chequerboard technique of studying antimicrobial interactions was assessed by testing a representative beta-lactam (piperacillin/tazobactam), aminoglycoside (gentamicin) and fluoroquinolone (ciprofloxacin) against themselves, that is piperacillin/tazobactam plus piperacillin/tazobactam, gentamicin plus gentamicin and ciprofloxacin plus ciprofloxacin. In addition, combinations of piperacillin/tazobactam plus gentamicin or ciprofloxacin were also tested against Enterobacteriaceae and Acinetobacter spp. in triplicate. The agar dilution chequerboard technique did not reliably show addition when agents were combined with themselves, and there was also considerable variation when beta-lactam plus aminoglycoside or fluoroquinolone combinations when tested in triplicate. These observations, and problems with the design of the method, indicate that the chequerboard technique should be used only with adequate controls and replication, and then interpreted with extreme caution; ideally, it should not be used as a method of assessing antimicrobial interactions. [ABSTRACT FROM AUTHOR]

Single oral doses of 250, 500, 750 and 1000 mg of sodium fusidate as one, two, three and four film-coated 250 mg tablets were compared in a cross over design trial with a solution dose of 500 mg in 12 healthy male volunteers. The effect of food on absorption of two-film coated tablets was also studied. Compared with the dose given as a solution, tablets gave complete oral absorption, the area under the curve (AUC) for blood concentration being virtually identical. After administration of 250, 500, 750 and 1000 mg the mean of the maximum serum concentrations (Cmax) was 11.6 +/- 1.1, 30.6 +/- 2.2, 48.1 +/- 3.0 and 65.2 +/- 4.2 mg/l, respectively, indicating a greater than expected increase in Cmax with increasing dose. This was also apparent with AUC, while there was a significant trend for beta, the terminal slope of the serum/concentration time curve, to decrease. Food significantly reduced Cmax and delayed Tmax but did not affect AUC or beta. Dosage had no effect on parameters of renal, hepatic or haemopoietic function but 25% of the volunteers complained of upper gastro-intestinal symptoms mainly at the highest dose studied. [ABSTRACT FROM AUTHOR]

Twelve healthy volunteers received single iv doses of either 500 and 1000 mg or 750 and 1500 mg of the sodium salt of FCE 22101; in addition, five of the volunteers received a further dose of 2000 mg. In the second part of the study, 11 of the volunteers received 1000 mg doses of FCE 22101 in a four-way randomized fashion by iv bolus (1000 mg, with and without probenecid), im injection (1000 mg plus lignocaine) and a continuous infusion (280 mg/h) to steady state. All doses were well tolerated by the volunteers with no serious side effects and no significant haematological or biochemical changes following drug administration. Plasma and urine concentrations of FCE 22101, and in the cross-over study also its open ring metabolites P1 and P2, were determined by HPLC. Good linearity was observed between the peak plasma levels or AUC and the dose given. Plasma concentrations were fitted to a two-compartment model and the mean pharmacokinetic parameters determined after iv bolus were: Cmax 117 mg/l, T½β 36 min, Vss 181, AUC 2179 mg/min/l with urinary recoveries of FCE 22101 37%, P1 36% and P2 6%. With probenecid the values were Cmax 116 mg/l, T½β 47min, Vss 141, AUC 4540 mg/min/l and urinary recoveries of FCE 22101 20%, P1 40% and P2 7%. Following im injection the mean values were Cmax 15 mg/l, Tmax 30 min, Tmax 14 min, T½β 61 min, AUC 2117 mg/min/l and urinary recoveries of FCE 22101 33%, P1 37% and P2 6%. At steady state during continuous infusion, mean values were Css 12.7 mg/l, Vss 131 and T½β after steady state was 22 min. Although urinary recoveries varied widely between volunteers there was a tendency towards consistency of recovery within individual volunteers. We conclude that FCE 22101 is a well tolerated penem with pharmacokinetic properties broadly similar to those of other penem and carbapenem antibiotics. [ABSTRACT FROM PUBLISHER]

A total of 5116 non-fastidious bacterial strains isolated from either blood or urine culture were collected from 20 geographically distributed centres within the UK. Upon receipt the strains were identified and the minimum inhibitory concentrations of ten antimicrobial agents in hospital usage were determined for each of the strains. All laboratories submitted a similar range of bacterial species and in species normally considered as sensitive the overall rates of resistance to the different antibiotics tested were: amikacin 2.4%, gentamicin 3.7%, netilmicin 2.6%, tobramycin 3.4%, ampicillin 41.7%, cefadroxil 11.6%, cefotaxime 1.4% [corrected], cefuroxime 4.3%, ciprofloxacin 0.6% and trimethoprim 13.0%. For those strains resistant to one or more aminoglycosides the mechanisms of resistance responsible were determined from the aminoglycoside-resistance patterns of the strains to 16 different aminoglycoside antibiotics. The predominant mechanisms of resistance found were APH(2") + AAC(6') production in staphylococci. AAC(2') production in Providencia spp., and AAC(3) production in the other Gram-negative genera. [ABSTRACT FROM AUTHOR]

A gene encoding AAC(6') mediated resistance to netilmicin and amikacin was cloned from the chromosome of a nosocomial strain of Serratia marcescens into the BamHI site of pACYC184. The resistance determinant was localized to a sequence of approximately 1 kb. A 490 base pair BamHI-PvuII restriction fragment from the cloned DNA was used as a probe in Southern hybridization studies. Homology with a 920 base pair fragment of PvuII digested S. marcescens DNA from AAC(6')-producing strains was observed. No homology was detected with aminoglycoside sensitive S. marcescens or Escherichia coli. [ABSTRACT FROM AUTHOR]

Solutions of vancomycin in phosphate-buffered saline, peritoneal dialysis effluent fluid and human serum were incubated at 37°C for ten days and sampled at daily intervals. The samples were assayed for vancomycin content by a microbiological assay, HPLC and polarisation fluoroimmunoassay (Abbott TDX). The results obtained by HPLC and microbiological assay agreed well and indicated approximately 50% loss over ten days in serum and buffered saline and over 70% loss in dialysate. TDX results indicated losses of only 20% and 40%, respectively. Degradation products were prepared from vancomycin by acid hydrolysis and purified by HPLC. These purified products were shown to cross-react in the TDX assay. It is suggested that the TDX assay becomes non-specific in the presence of vancomycin breakdown products and thus overestimates true vancomycin concentrations. [ABSTRACT FROM PUBLISHER]

Eight patients aged over 65 years (mean age 81 years), with microbiologically proven urinary tract infections were treated with 400 mg norfloxacin bd daily for six days. Blood samples were taken on day 1 and day 6 to give a concentration-time profile, and on each of the other days samples were obtained before the first dose of the day. Urine was collected throughout. The mean of the maximum serum concentration of norfloxacin after the first dose was 1.5 mg/l (range 1.1–1.8 mg/l) at a mean of 3.2 h (range 1–6 h). After the last dose the mean maximum concentration was 2.2 mg/l (range 1.6–3.7 h) at 3 h (range 1–4 h). The mean serum half life was 5 h (range 3.7– 6 h) on day 1 and 5.3 h range (4.4–6.2 h) on day 6. Serum pre-dose norfloxacin levels showed no evidence of accumulation. Mean urinary concentrations varied between 95 and 288 mg/l from day 1 to day 6. No significant adverse reactions were noted. No alteration of norfloxacin dose is suggested in the aged with normal renal function. [ABSTRACT FROM PUBLISHER]

The in-vitro activity of CGP 31608 (hereinafter termed CGP), a new penem, was tested by an agar dilution technique in comparison with imipenem, Sch 34343, cefotaxime, ceftazidime, aztreonam, ampicillin, gentamicin and ciprofloxacin. 480 clinical isolated were tested, some of which were selected because of their multiple resistance. CGP showed consistent activity against a wide range of species, having MIC90 values of 2-8 mg/l for almost all Enterobacteriaceae, Pseudomonas spp., Haemophilus spp., Corynebacterium spp. and Bacteroides spp. It was the most active agent tested against staphylococci having an MIC90 of 0.25 mg/l, showing no reduction in activity against methicillin-resistant strains. Lesser activity was observed against some streptococci, Proteus spp. and clostridia. Tests carried out in broth demonstrated that CGP activity was constant over a pH range of 6-8 and was unaffected by the presence of 50% serum or 50% urine. The rate of killing of CGP, gentamicin, cefotaxime and ciprofloxacin was investigated in broth against log and stationary-phase cultures of Staphylococcus aureus and Escherichia coli. The most rapid rate of kill was seen with ciprofloxacin, while CGP exhibited a more rapid bactericidal effect than cefotaxime against Staph. aureus. The stability of CGP was studied at two concentrations in serum, broth and phosphate buffer at 4 degrees C, room temperature and 37 degrees C. In serum the half-life was 112 h at 4 degrees C, 35 h at room temperature and 11.4 h at 37 degrees C. Protein binding tested at concentrations of 5-100 mg/l was 2-6.3%. [ABSTRACT FROM AUTHOR]

A method is described for the detection and identification of two aminoglycoside-acetylating (AAC(2') or AAC(3) or AAC(6')) or -phosphorylating (APH(2”) or APH(3') enzymes when these are present in the same crude enzyme extract. Crude enzyme extracts were prepared from reference strains of bacteria producing AAC(2'), AAC(3), AAC(6'), APH(2”) or APH(3') enzymes and mixed to give the following paired enzyme combinations: AAC(2')+AAC(3), AAC(2')+AAC(6'), AAC(3)+AAC(6') and APH(2”)+APH(3'). These enzyme mixtures were examined by the radioenzymatic profile method for the identification of aminoglycoside-modifying enzymes and their reaction products with butirosin, lividomycin and kanamycin (AAC) or lividomycin and kanamycin (APH) characterized by high performance liquid chromatography (HPLC). Only two of the eight enzymes present were identified by the radioenzymatic method, but all eight were correctly identified by the HPLC method. [ABSTRACT FROM PUBLISHER]

The pharmacokinetics of a single intravenous dose of cefotetan were studied in 17 volunteer patients with end-stage renal failure, requiring intermittent haemodialysis in 12 cases or undergoing continuous ambulatory peritoneal dialysis in 5 cases. Between haemodialysis the mean plasma elimination half life was 20.4 h (S.E.M.±2.1). This decreased to 7.5 h (S.E.M.±0.6) during haemodialysis. In patients treated by continuous ambulatory peritoneal dialysis the mean plasma elimination half life was 15.5 h (S.E.M.±1.9). Small amounts of cefotetan (5–9% of the administered dose) were recovered in the peritoneal dialysates removed over the 24 hfollowing the dose. [ABSTRACT FROM PUBLISHER]

A high performance liquid chromatographic method is described for the assay of chloramphenicol acetyltransferase activity which detects the formation of both 3-acetoxy chloramphenicol and 1,3-diacetoxy chloramphenicol. In experiments performed at pH 6.8 only 3-acetoxy chloramphenicol was detected while in experiments performed at pH 7.8 both 3-acetoxy and 1,3-diacetoxy chloramphenicol were detected. [ABSTRACT FROM PUBLISHER]

A method is described for the identification of the aminoglycoside-phosphorylating (APH) enzymes APH(2″) and APH(3′) by the high performance liquid chromato-graphic (HPLC) identification of their products of reaction with kanamycin and ATP. Twelve reference strains which produce either APH(2″) or APH(3′) were examined by both this method and the radioenzymatic profile method; correct enzyme identification was made with 12/12 of the strains by the HPLC method and 11/12 of the strains by the radioenzymatic profile method. Reaction products of APH(2″) or APH(3′) with ATP and butirosin, geneticin, lividomycin, ribostamycin, sissomicin or tobramycin were also characterized by HPLC. Conditions for their chromatography are given. [ABSTRACT FROM PUBLISHER]

Using an agar dilution technique we examined the in-vitro activity of Sch 34343 against 485 clinical bacterial isolates. Ampicillin, mezlocillin, cefuroxime, cefotaxime, cefotetan, ceftazidime, ceftriaxone, imipenem (N-formimidoyl thienamycin) and gentamidn were used for comparison. Sch 34343 exhibited activity against all species tested, excepting Pseudomonas aeruginosa and Pseudomonas species. Unlike many newer β-lactams, Sch 34343 was highly active against Gram-positive species. It was consistently active against the Enterobacteriaceae, with MIC50 and MIC90 being usually closely similar, as were results with two inoculum sizes (104 and 106 cfu). This, together with its activity against strains resistant to many other β-lactam agents, suggested high stability to β-lactamases. Sch 34343 was the most active compound tested against Bacteroides fragilis. In tests of combined bacteristatic action with gentamidn no synergy was seen. It had bactericidal action in broth culture, against sensitive strains of E. coli, Klebstella pneumoniae, Staphylococcus aureus and Streptococcus faecalis. It showed good stability in aqueous solution and serum at low temperatures at pH values in the physiological range, and was moderately stable at 37°C. Binding in human plasma was 72%.We concluded that Sch 34343 is a highly promising agent with a broad spectrum of activity making it potentially suitable as monotherapy for patients with infection of undetermined bacterial aetiology, particularly if Bact. fragilis is a possible pathogen. [ABSTRACT FROM PUBLISHER]

A two-compartment in-vitro model is described in which the compartments are separated by a hollow-fibre dialyser. It was used successfully to simulate the 2-compartment kinetics of intravenously administered ciprofloxacin and to observe the activity of ciprofloxacin against a strain of Serratia marcescens growing in the peripheral compartment Because of the complexity of the apparatus, however, the experiments were labour-intensive, prone to break-down, and gave results only slowly. There was a possibility that drug-resistant variants were carried over from one experiment to the next by re-use of the dialyser. While the model could give very flexible kinetics and retained all of the culture, there were constraints on the variations in kinetics from the physical sizes of the compartments and practicable flow rates. An ever-present problem was the possibility of fluid diafiltering rapidly into either compartment Such a model should perhaps only be used when a very short drug half-life is to be simulated or very flexible kinetics required. Simpler, multichannel equipment could be more productive. [ABSTRACT FROM PUBLISHER]

The activity of enoxacin against 362 clinical bacterial isolates in comparison with norfloxacin, nalidixic acid, ampicillin, latamoxef (moxalactam) and gentamicin was tested by an agar dilution method. Typical MICs for enterobacteria lay between 0.12 and 1.0 mg/1. Enterobacter spp. and Serratia spp. tended to be more resistant. Enoxacin was also active against Pseudomonas aeruginosa (mean MIC 0.5 mg/1) and highly active against fastidious Gram-negative aerobes. Typical MICs for Staphylococcus aureus were 1.2 mg/1 while streptococci were more resistant (16–32 mg/1). Enoxacin had no useful activity against Bacteroides fragilis and Clostridium perfringens. Enoxacin was generally more active at pH 8 than pH 6, and in broth than in urine. It was bactericidal in its action. Daily serial passage from growth in broth containing enoxacin caused decreased sensitivity which was limited to four- to 16-fold greater than the original MIC. Enoxacin was about half as active as norfloxacin against enterobacteria, equally active against staphylococci, and some two to four times less active against streptococci. [ABSTRACT FROM PUBLISHER]

Cefotaxime was given to neonates as treatment of infection in a dose of 25 mg/kg 12 hourly by intravenous injection. Blood samples taken by heel-prick were specially treated to minimize any effect of haemolysis on the hydrolysis of cefotaxime. The mean peak plasma concentrations of cefotaxime on the first, second and third days of therapy were 43, 40 and 52 mg/1, respectively, with mean plasma half lives of 40, 2.7 and 3.2 h. The mean peak concentrations of desacetyl-cefotaxime were about a quarter of those of cefotaxime, which is in good agreement with adult studies, but much lower than those previously published in studies with neonates.These results emphasize the care that is necessary in the assay of body fluids and tissues for cefotaxime and desacetyl-cefotaxime if accurate results are to be obtained. [ABSTRACT FROM PUBLISHER]

Ciprofloxacin is a new antibacterial agent of the 4-quinolone group. With an agar dilution technique we compared its activity on 365 clinical isolates with those of norfloxacin, nalidixic acid, ampicillin, mezlocillin, cefadroxil, cefuroxime, ceftazidime, ceftriazone , cefotaxime, latamoxef (moxalactam), and gentamicin. Ciprofloxacin was overall the most active agent tested against aerobic Gram-negative species, with the MIC90 values for all species being below 1 mg/l (excepting Providencia stuartii with 4 mg/l), and the large majority being below 0.12 mg/l. Many of the strains were selected on the basis of resistance to beta-lactam agents or gentamicin, and ciprofloxacin was also active against these. There was little difference in the activity of ciprofloxacin at inocula of 10(4) or 10(6) cfu. Strains with higher MIC's of the related agents norfloxacin and nalidixic acid were less susceptible to ciprofloxacin . Ciprofloxacin was less active against Gram-positive species (typical MIC90 values were 0.5 or 1 mg/l) and obligate anaerobes (4 mg/l for Bacteroides fragilis). The activity of ciprofloxacin in broth dilution tests was little affected by pH over the range 6.0-8.0, or by human serum or tissue fluid; its activity was reduced by the presence of urine. Binding to human serum protein was 20-28%. Ciprofloxacin was rapidly bacterial in broth at concentrations near to its MICs. By exposure to subinhibitory concentrations of ciprofloxacin it was possible to increase its MIC for bacteria in daily subcultures. The final MIC values after ten days were often about 16-fold greater than those observed initially. [ABSTRACT FROM AUTHOR]

The efficacy, tolerability and side effects of a 3-day treatment for acute urinary infection in general practice with norfloxacin (400 mg 12 hourly) or nalidixic acid/citrate (1 sachet 8 hourly) were compared in a randomized study. Patient groups had similar demography, symptomatology and initial infecting bacteria. Of the evaluable 55 patients in each treatment group with initial bacteriuria, 53 (96%) had no bacteriuria at immediate follow-up after treatment with norfloxacin and 45 (82%) with nalidixic acid/citrate. The corresponding rates at late follow-up were 40/45 (89%) and 29/43 (67%) (P < 0.05). Among the bacteriuric patients a significantly greater proportion were recorded as having cured and improved symptoms. The tolerability of norfloxacin seemed to be better than that of nalidixic acid/citrate. [ABSTRACT FROM PUBLISHER]

A substrate-labelled fluoroimmunoassay (SLFIA) for gentamicin was used to assay netilmicin by substituting serum calibrators containing netilmicin. The assay proved highly reproducible and the results obtained showed a good correlation with the results of EMIT and microbiological assays. [ABSTRACT FROM AUTHOR]

SUMMARY The concentration of trimethoprim in the prostatic fluid, collected by means of pilocarpine stimulation from dogs with urinary diversions, was found to be two to three times higher than that in simultaneous serum specimens. The importance of this finding in relation to the treatment of human prostatitis is discussed and the conclusion reached that the drug merits a clinicomicrobiological trial in the treatment of prostatic infections. [ABSTRACT FROM AUTHOR]