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PubMed1984

Enoxacin: worldwide in-vitro activity against 22451 clinical isolates.

A worldwide multicentre study involving 31 centres in eight countries was conducted to compare the in-vitro activity of enoxacin with that of other currently available antibiotics. Enoxacin was active against virtually all of the species of Enterobacteriaceae tested (MIC90 less than or equal to 0.25-2 mg/l). It was also effective at inhibiting Pseudomonas aeruginosa (MIC90 = 2 mg/l; n = 3540), Staphylococcus aureus and epidermidis (MIC90 = 2 mg/l; n = 2635 and 837 resp.), Acinetobacter calcoaceticus (MIC90 = 4 mg/l; n = 260), Neisseria gonorrhoeae and Haemophilus influenzae (both MIC90 less than or equal to 0.25 mg/l). The MIC90 for enoxacin against streptococci ranged from 8 to 32 mg/l. Comparison of data from Canada, West Germany, U.K., South Africa and New Zealand showed the MICs for enoxacin to be generally consistent throughout the world. The only exception was for Citrobacter freundii where the MIC90 was significantly higher in the U.K. than in West Germany (P less than 0.05 Mann Whitney U Test). Against susceptible species the activity of enoxacin was generally greater than that of ampicillin, gentamicin and the cephalosporins. Because of the prevalence of resistance to these drugs, there appears to be a continued need for new antibiotics with differing mechanisms of action.

Bacteria↗

PubMed1985

Comparative activity of the penem antibiotic Sch 34343 against gram-negative and gram-positive bacteria with special reference to multiresistant strains.

A new penem antibiotic, Sch 34343, was shown to be active against a large number of Gram-positive bacteria. The drug inhibited penicillinase-positive and -negative staphylococci equally well, being five times more active than cefamandole and ten times more active than methicillin. Most methicillin-resistant staphylococci were inhibited by concentrations between 0.25 and 4 mg/l, but a small group of highly resistant strains were observed. Sch 34343 was eight times less active than ampicillin and penicillin G, but as active as piperacillin against enterococci. The drug showed excellent activity against various streptococci. Sch 34343 was as bactericidal as flucloxacillin, ampicillin and penicillin G against staphylococci, enterococci and streptococci, respectively, in killing kinetic tests. Enterobacteriaceae susceptible to third-generation cephalosporins were approximately five times less susceptible to Sch 34343, but MICs were far below the susceptibility breakpoint. Sch 34343 was equally active against Citrobacter and Enterobacter strains that were highly resistant to third-generation cephalosporins and to aztreonam. Together with thienamycin, this drug seems to be a good alternative for the treatment of infections caused by bacteria resistant to third-generation cephalosporins and to aztreonam.

Anti-Bacterial Agents↗

PubMed1985

Sch 34343 activity against streptococci and beta-lactam-resistant Enterobacteriaceae.

The in-vitro activity of Sch 34343 was compared with that of cefotaxime, ceftazidime, latamoxef (moxalactam), aztreonam and ampicillin. Against pneumococci, Sch 34343 was as active as ampicillin, whereas against the other streptococci it was less active than ampicillin but significantly better than the other antibiotics against enterococci. With clinical isolates of Enterobacteriaceae resistant to cefotaxime, Sch 34343 had MICs generally less than 2 mg/l. After introduction of plasmid-mediated beta-lactamases into Escherichia coli Cla. there were no significant changes in the MICs of Sch 34343. Mutants of Enterobacter cloacae, Citrobacter freundii and Morganella morganii with derepressed cephalosporinases had susceptibilities equal to or less than 1 mg/l, which were generally lower than those of the other compounds tested. Comparison of parental strains and permeability mutants of E. coli, Ent. cloacae, and Serratia marcescens showed that the increase in MICs of Sch 34343 were lower than those found for the other antibiotics.

Anti-Bacterial Agents↗

PubMed1985

Sch 34343: in-vitro antibacterial activity and susceptibility to beta-lactamases.

The in-vitro activity of the penem Sch 34343 was assessed in comparison with third-generation cephalosporins, aztreonam and imipenem. Sch 34343 was active, with MICs generally 2 mg/1 or less, against a broad spectrum of organisms amongst which were staphylococci (including methicillin-resistant strains), streptococci (though enterococci were less susceptible with Sch 34343 MICs mostly 4-8 mg/1), anaerobes (including the Bacteroides fragilis group), Haemophilus influenzae and Neisseria gonorrhoeae. It was also active against the Enterobacteriaceae though Enterobacter cloacae and Serratia spp. were somewhat less susceptible than other members of this group. Sch 34343 lacked useful activity against most species of Pseudomonas (including Ps. aeruginosa) but was active against Ps. acidovorans and some isolates of Ps. cepacia. Sch 34343 showed a high degree of resistance to plasmid-determined and most chromosomally-determined beta-lactamases; however, it was hydrolysed rapidly by enzymes from some isolates of Aeromonas hydrophila and more slowly by enzymes from Ps. maltophilia and Bact. melaninogenicus subspecies intermedius. We did not observe any reduction in sensitivity to Sch 34343 for most beta-lactamase-producing organisms, including strains of Enterobacter spp. and Citrobacter freundii that were resistant to most other beta-lactams.

Aeromonas↗

PubMed1985

Multiple antibiotic resistance plasmids in Enterobacteriaceae isolated from diarrhoeal specimens of hospitalized children in Indonesia.

We studied the plasmid and antibiotic resistance characteristics of 35 strains of Enterobacteriaceae recovered from faecal specimens of children with diarrhoea in Central General Hospital, Bandung, Indonesia. Twenty three Escherichia coli, three Providencia, three Proteus, three Klebsiella, two Enterobacter and one Citrobacter were examined. All strains were multiply resistant, many carrying six to nine antibiotic resistances. Most of these resistances were transferable to a laboratory E. coli strain and were carried on large-sized plasmids. All recently-described tetracycline resistance determinants (Classes A----D) were represented; the most common was the Class B, or TN10 type. The TEM-1 beta-lactamase was detected in 17 out of 21 ampicillin-resistant strains examined. The OXA-1, PSE-1, and SHV-1 enzymes were also found. Of 23 plasmids tested, all could be classified into one of eight different incompatibility groups: IncFII, IncN, IncB, IncF1, IncI1, IncI2, IncH2 and IncT. These studies demonstrate the existence of large multiresistant transferable plasmids representing common incompatibility groups and bearing common tetracycline and ampicillin resistance determinants in enteric strains isolated from children hospitalized in Indonesia.

Child↗

PubMed1986

Inducible type I beta-lactamases of gram-negative bacteria and resistance to beta-lactam antibiotics.

Mutants, showing either constitutive (depressed) or non-inducible expression of chromosomally-mediated Type I beta-lactamase were obtained from clinical isolates of Enterobacter cloacae, Ent. aerogenes, Citrobacter freundii, Providencia stuartii, Morganella morganii, Serratia marcescens and Pseudomonas aeruginosa. The wild-type and mutant strains were compared for susceptibility to a range of beta-lactam antibiotics. Derepression of beta-lactamase synthesis generally, but not always, resulted in a marked reduction in susceptibility to the agents tested, including the '3rd generation' cephalosporins. In many cases, the observed resistance would preclude, or severely compromise, the therapeutic efficacy of the drugs. In this context, depressed mutants of Enterobacter spp., Citro. freundii and Ps. aeruginosa could be of primary concern although those of Ser. marcescens, Prov. stuartii and Morg. morganii often exhibited equally high resistance levels to older beta-lactams. Comparison of the susceptibilities of the non-inducible mutants with that of their inducible parents suggested variation in the beta-lactamase inductive potency of different compounds in different organisms. For example, cefoxitin was a powerful inducer in Ent. cloacae, Citro. freundii and one strain of Ps. aeruginosa; similarly cefazolin and cefuroxime were good beta-lactamase inducers in Ser. marcescens and Morg. morganii. Aminothiazolyl-oxime cephalosporins and ureido-penicillins were generally poor inducers. From such comparisons, the contribution of inducible Type I beta-lactamase to resistance phenotype could be ascertained.

Anti-Bacterial Agents↗

PubMed1986

The activity of BMY 28142 a new broad spectrum beta-lactamase stable cephalosporin.

The in-vitro activity of BMY 28142, an iminomethoxy, aminothiazolyl cephalosporin containing a methyl pyrrolidinio C-3 was compared with that of cefotaxime, ceftazidime, aztreonam, imipenem and tobramycin against various bacteria. BMY 28142 was the most active agent tested against the Enterobacteriaceae inhibiting 90% at less than or equal to 1 mg/l. The in-vitro activity of BMY 28142 was equal to or superior to cefotaxime against the highly susceptible members of the Enterobacteriaceae and several-fold superior to ceftazidime and aztreonam. BMY 28142 inhibited many Enterobacter cloacae, Citrobacter freundii and Serratia marcescens resistant to cefotaxime, ceftazidime and aztreonam. BMY 28142 was more active than imipenem against Proteus, Providencia and Morganella species. Ceftazidime and imipenem were more active than BMY 28142 against Pseudomonas aeruginosa, but it inhibited piperacillin and tobramycin-resistant isolates. BMY 28142 inhibited beta-lactamase producing Haemophilus influenzae and Neisseria gonorrhoeae. BMY 28142 was more active than ceftazidime against streptococcal and staphylococcal species, but it did not inhibit or kill most methicillin-resistant Staphylococcus aureus. BMY 28142 did not inhibit most Bacteroides species. BMY 28142 was not hydrolyzed by common plasmid and chromosomal beta-lactamases, but it bound poorly to Enterobacter beta-lactamase, was a poor inhibitor of the TEM plasmid beta-lactamase and was a poor inducer of beta-lactamases.

Anti-Bacterial Agents↗

PubMed1986

In-vitro activity of ticarcillin with and without clavulanic acid against clinical isolates of gram-positive and gram-negative bacteria.

The in-vitro activity of ticarcillin with and without clavulanic acid was investigated against 285 freshly isolated clinical strains of Gram-positive and Gram-negative bacteria by the agar-dilution technique on Mueller-Hinton-agar. Clavulanic acid had an excellent or moderate potentiating effect on the in-vitro activity of ticarcillin against staphylococci, Escherichia coli, Klebsiella spp., Enterobacter aerogenes, Proteus mirabilis, Citrobacter spp., Acinetobacter, Haemophilus influenzae and Bacteroides spp. No effect was seen against enterococci, indole-positive Proteus spp., Ent. cloacae, Serratia marcescens and Pseudomonas aeruginosa. The effect of clavulanic acid was dose- and inoculum-dependent.

Bacterial Infections↗

PubMed1986

Susceptibility of ticarcillin-resistant gram-negative bacilli to different combinations of ticarcillin and clavulanic acid.

The susceptibility of ticarcillin-resistant and of ticarcillin-susceptible Gram-negative bacilli to different combinations of ticarcillin and clavulanic acid has been investigated. Susceptibility to ticarcillin has been restored in ticarcillin-resistant isolates in proportion to the amount of clavulanic acid in the combination and depending upon the species. The decrease in the MICs of ticarcillin was excellent to good in Proteus, Morganella, Providencia, Escherichia coli and Klebsiella, moderate in Enterobacter, Citrobacter and Serratia, but poor in Pseudomonas aeruginosa. An unfavourable effect of clavulanic acid on the MICs of ticarcillin was observed in some isolates belonging to species with inducible beta-lactamases.

Clavulanic Acid↗

PubMed1986

The in-vitro activity and beta-lactamase stability of carumonam.

Carumonam is a monobactam with a beta-carbamyloxmethyl group at position 4. It inhibited 90% of Enterobacteriaceae at less than or equal to 8 mg/l and had in-vitro activity similar to that of cefotaxime, ceftazidime and aztreonam. Fifty per cent of Enterobacter, Citrobacter and Serratia isolates were inhibited by 4 mg/l, but isolates resistant to aztreonam and ceftazidime were not inhibited. Carumonam, like aztreonam, did not inhibit Gram-positive or anaerobic species. Carumonam was not destroyed by the common plasmid- and chromosomally-mediated beta-lactamases and was more stable than aztreonam to attack by the K-1 beta-lactamase of Klebsiella oxytoca. Carumonam inhibited Richmond-Sykes type Ia and Id beta-lactamases but was a poor inhibitor of type III enzymes. It did not induce beta-lactamases.

Anti-Bacterial Agents↗

PubMed1986

Comparative activities of the beta-lactamase inhibitors YTR 830, clavulanate and sulbactam combined with extended-spectrum penicillins against ticarcillin-resistant Enterobacteriaceae and pseudomonads.

The in-vitro synergistic activity of YTR 830, a new beta-lactamase inhibitor, combined with four extended-spectrum penicillins (ticarcillin, piperacillin, mezlocillin and apalcillin) against ticarcillin-resistant clinical isolates of Gram-negative enteric bacilli was compared with that of clavulanate and sulbactam. Synergy testing was performed with fixed concentrations of beta-lactamase inhibitors (8 mg/l) combined with doubling dilutions of beta-lactams in microdilution trays. Synergy was defined as a four-fold or greater decrease of beta-lactam MIC in the combination compared with the beta-lactam alone. For 79 ticarcillin-resistant Enterobacteriaceae, ticarcillin-YTR 830 and ticarcillin-clavulanate were synergistic against 90% of strains; for ticarcillin-sulbactam, 70% showed synergy. The synergistic activity of all three inhibitors was similar against strains resistant only to ticarcillin; for strains resistant to all four extended-spectrum penicillins, the activity of ticarcillin with YTR 830 and clavulanate was similar (synergy against 79% of strains) and superior to ticarcillin-sulbactam (synergy against 39% of strains). YTR 830 was more active than clavulanate against Serratia, Citrobacter, Proteus and Providencia spp. Piperacillin, mezlocillin and apalcillin susceptible strains, with MICs of 8-16 mg/l, showed synergy with inhibitors against 37-87% of strains. Amongst pseudomonads, no synergy was demonstrated against Pseudomonas aeruginosa; ticarcillin produced synergy with the inhibitors against Ps. maltophilia, while piperacillin-YTR 830 and apalcillin-YTR 830 were synergistic against Ps. cepacia. YTR 830 appears to have comparable in-vitro activity to that of clavulanate, and further development of this compound is warranted.

Ampicillin↗

PubMed1986

Evaluation of imipenem/cilastatin against nosocomial infections and multiresistant pathogens.

Thirty-five patients suffering from soft tissue infections (12), upper UTIs (6), bronchopneumonia (6), septicaemia (2), chronic osteomyelitis (2), intra-abdominal abscess (2), liver abscess (1), lung abscess (1), acute cholangitis (1), thoracic empyema (1) and chronic prostatitis (1) were given imipenem/cilastatin for 6-21 days. In 22 patients several aggravating factors coexisted, while infection in 16 patients was polymicrobial. The following pathogens were implicated: Pseudomonas aeruginosa (21), Escherichia coli (15), Enterobacter cloacae (6), Proteus spp. (3), Klebsiella pneumoniae(3), Citrobacter freundii (1), Salmonella enteritidis (1), Acinetobacter spp. (4), Haemophilus influenzae (2), Bacteroides fragilis (1) and Peptococcus saccharolyticus (1) with MICs to imipenem ranging between 0.5 and 8 mg/l. A successful clinical response was observed in 91.4% of the patients, while pathogens were eradicated in 75.9%, persisted in 24.2% and recurred, in 9.1% of patients, with development of resistance to imipenem in two Ps. aeruginosa strains. Against 150 multiresistant strains of Ps. aeruginosa, 40% of which were resistant to amikacin, 86.4% and 88.9% were found sensitive to ceftazidime and imipenem respectively. It is concluded that imipenem provides the possibility of treating successfully multiresistant and polymicrobial infections with a single antimicrobial.

Adult↗

PubMed1987

In-vitro activity of two new quinolone antimicrobial agents, S-25930 and S-25932 compared with that of other agents.

S-25930 and S-25932, two new 4-quinolones, were compared to ciprofloxacin, enoxacin, ofloxacin, norfloxacin, cefotaxime, gentamicin, trimethoprim, and ampicillin. S-25930 and S-25932 inhibited 90% of Enterobacteriaceae at less than or equal to 1 mg/l, usually differing only two-fold. The MIC90 for Pseudomonas aeruginosa was 8 mg/l for S-25930 and 16 mg/l for S-25932, compared to MICs of 1 to 8 for the other four quinolones. Both drugs inhibited Enterobacter cloacae, Serratia marcescens and Citrobacter freundii resistant to cefotaxime and Klebsiella species resistant to gentamicin and trimethoprim. The MICs90 were 0.125 and 0.25 mg/l against staphylococci, including methicillin-resistant Staphylococcus aureus and were superior to the MICs of other quinolones; activity against haemolytic streptococci at 1-2 mg/l was also superior. S-25930 and S-25932 showed rapid bactericidal activity at the MBC concentration and both agents showed post-antibiotic suppression of growth of bacteria. The agents were active in acid medium, but activity was reduced by magnesium at 9 mM. A stepwise increase in resistance was produced by serial passage in increasing concentrations of drug.

Anti-Bacterial Agents↗

PubMed1987

Enteric colonization with antibiotic resistant bacteria in nurses working in intensive care units.

To determine whether nurses who worked in an intensive care unit (ICU) might acquire enteric colonization with Gram-negative aerobic bacteria from their patients, rectal swabs were obtained from the patients and nurses in the ICU, from nurses working in a coronary care unit (CCU) and from young women with urinary tract infection who had not been exposed to the hospital environment. The healthy women differed from the patients in that their enteric flora contained greater numbers of lactose fermenting bacteria, they were less often colonized by resistant organisms and when resistant bacteria were present they were less abundant than in the patients. Nurses who had been treated with antimicrobial agents during the preceding six months were colonized more often with antibiotic resistant enteric bacteria. There was no evidence of transmission of antibiotic resistant Escherichia coli from patients to nurses largely because this species had been virtually eliminated from the patients by intensive use of antimicrobial agents. Instead, several multiresistant species of Klebsiella, Citrobacter and Pseudomonas were isolated from the patients and ICU nurses. It was difficult, however, to define clearly patient-nurse controls who had no exposure to the ICU patients. These observations and those of other investigators emphasize the need for examination of control populations and of therapeutic use of antibiotics when examining the issue of environmental acquisition of antibiotic resistant bacteria.

Adolescent↗

PubMed1988

Ceftazidime combined with mecillinam: serum bactericidal titres compared with in-vitro synergy against gram-negative bacilli.

In a study of the possible interaction between mecillinam and ceftazidime against Gram-negative bacilli, ten volunteers received on separate days: ceftazidime 20 mg/kg iv in 15 min, mecillinam 10 mg/kg iv in 15 min, or the combination. Blood samples were obtained before and 1 and 6 h after the end of the infusion. Ten strains each of Klebsiella pneumoniae, Serratia marcescens, Citrobacter freundii, Salmonella spp. and Yersinia spp. and nine strains each of Acinetobacter spp., and Pseudomonas aeruginosa were selected. Most of the strains were resistant to ampicillin and cefazolin. Serum levels of ceftazidime and mecillinam were measured by bioassay. Serum bacteriostatic (SBS) and bactericidal (SBA) titration was done in microtitre plates in cation supplemented Mueller-Hinton broth and 50% human serum. Chequerboard titration was also studied to assess in-vitro synergy between ceftazidime and mecillinam in Mueller-Hinton broth with or without 50% serum. The mean serum concentrations (SD) were for mecillinam: 6.1 (1.7) at 1 h, and less than 0.3 at 6 h and for ceftazidime: 36.3 (5.5) at 1 h and less than 5 at 6 h. Identical concentrations were measured for the combination. By chequerboard titration, no synergy occurred for Acinetobacter spp. and Ps. aeruginosa, whereas it was observed in 37/60 (FIC) and 33/60 (FBC) of the strains of other species in Mueller-Hinton; from the strains showing synergy, 28/37 (FIC) and 30/33 (FBC) showed also synergy in Mueller-Hinton with 50% human serum. In SBS and SBA, on the other hand, the combination of mecillinam with ceftazidime showed an additive effect against most Enterobacteriaceae tested, synergy being shown for only 10-35% of tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Amdinocillin↗

PubMed1988

Activity of temocillin and other penicillins against beta-lactamase-inducible and -stably derepressed enterobacteria.

MICs of temocillin, carbenicillin, ticarcillin, mezlocillin, piperacillin and ampicillin were determined for mutant series of Enterobacter cloacae, Citrobacter freundii, Proteus vulgaris, Morganella morganii and Serratia marcescens with inducible, stably derepressed or basal expression of chromosomal Class I beta-lactamases. Ampicillin was inactive (MIC greater than 256 mg/l) both against beta-lactamase-inducible organisms (except C. freundii) and their stably derepressed mutants, whereas basal mutants were sensitive (MIC 2-8 mg/l). Carbenicillin, ticarcillin, mezlocillin, piperacillin (and ampicillin for C. freundii) were active against both inducible and basal organisms (MIC less than 16 mg/l), but inactive against the derepressed mutants (MICs usually greater than 64 mg/l). Temocillin inhibited all the organisms, including the stably derepressed mutants, at 16 mg/l. Derepressed S. marcescens, M. morganii and Pr. vulgaris were as susceptible as the inducible strains and basal mutants. MICs of temocillin for derepressed mutants of E. cloacae and C. freundii were 4-16 fold above those for their inducible parent strains, but remained within the clinical range.

Enterobacteriaceae↗

PubMed1988

Comparative in-vitro activity of tigemonam, a new monobactam.

The in-vitro activity against Gram-negative aerobic bacterial pathogens of a new oral monobactam, tigemonam, was compared with those of amoxycillin/clavulanic acid, aztreonam, cefaclor, ceftazidime, cefuroxime, ciprofloxacin, co-trimoxazole and gentamicin, by an agar-dilution method. Tigemonam inhibited 90% of strains tested of Escherichia coli, Klebsiella spp., Proteus spp., Salmonella spp., Haemophilus influenzae and Branhamella catarrhalis at concentrations of 0.25 mg/l or below. The MIC90 for Enterobacter spp. was 16 mg/l and for Citrobacter 4 mg/l. Pseudomonas aeruginosa was resistant to tigemonam but susceptible to aztreonam. In comparison with the other oral antibiotics tested, tigemonam was generally more active. Tigemonam showed minimal inoculum dependence, between 10(2) and 10(6) cfu per spot. It is concluded that tigemonam is a candidate for clinical trials in patients with infections caused by Gram-negative aerobes other than pseudomonas and acinetobacter.

Anti-Bacterial Agents↗

PubMed1988

Antimicrobial activity of LY163892, an orally administered 1-carbacephem.

LY163892 was found to be similar to cefaclor and slightly superior to cephalexin in antimicrobial activity and spectrum. Bacteria with MIC50 less than or equal to 8.0 mg/l included Escherichia coli, Klebsiella spp., Proteus mirabilis, Citrobacter diversus, Haemophilus influenzae, Branhamella catarrhalis, pathogenic Neisseria spp., oxacillin-susceptible staphylococci, and Streptococcus spp. Strains that produced plasmid-mediated beta-lactamases generally remained susceptible to LY163892. LY163892 was found to be bactericidal in general, but its MICs for some bacterial strains were adversely affected by increased inocula.

Bacteria↗