Search PubMed⌕ Search

Biomedical subjects

D M Livermore

Publications and source records attributed to D M Livermore.

At least 109 records · Page 6Linked to original sources
PubMed1998

OXA-16, a further extended-spectrum variant of OXA-10 beta-lactamase, from two Pseudomonas aeruginosa isolates.

Two extended-spectrum mutants of the class D beta-lactamase OXA-10 (PSE-2) from Pseudomonas aeruginosa isolates obtained in Ankara, Turkey, were described previously and were designated OXA-11 and -14. P. aeruginosa 906 and 961, isolated at the same hospital, were highly resistant to ceftazidime (MIC >/= 128 microgram/ml) and produced a beta-lactamase with a pI of 6.2. The MICs of ceftriaxone, cefoperazone, cefsulodin, and cefepime were 4- to 16-fold above the typical values for P. aeruginosa, whereas the MICs of penicillins and cefotaxime were raised only marginally. Ceftazidime MICs were not significantly reduced by clavulanate or tazobactam at 4 microgram/ml. Ceftazidime resistance did not transfer conjugatively but was mobilized to P. aeruginosa PU21 by plasmid pUZ8. Both isolates gave similar DNA restriction patterns, suggesting that they were replicates; moreover, they yielded identically sized BamHI fragments that hybridized with a blaOXA-10 probe. DNA sequencing revealed that both isolates had the same new beta-lactamase, designated OXA-16, which differed from OXA-10 in having threonine instead of alanine at position 124 and aspartate instead of glycine at position 157. The latter change is also present in OXA-11 and -14 and seems critical to ceftazidime resistance. Kinetic parameters showed that OXA-16 enzyme was very active against penicillins, cephaloridine, cefotaxime, and ceftriaxone, but hydrolysis of ceftazidime was not detected despite the ability of the enzyme to confer resistance.

Amino Acid Sequence↗
PubMed1998

Interactions of beta-lactamases with sanfetrinem (GV 104326) compared to those with imipenem and with oral beta-lactams.

Sanfetrinem is a trinem beta-lactam which can be administered orally as a hexatil ester. We examined whether its beta-lactamase interactions resembled those of the available carbapenems, i.e., stable to AmpC and extended-spectrum beta-lactamases but labile to class B and functional group 2f enzymes. The comparator drugs were imipenem, oral cephalosporins, and amoxicillin. MICs were determined for beta-lactamase expression variants, and hydrolysis was examined directly with representative enzymes. Sanfetrinem was a weak inducer of AmpC beta-lactamases below the MIC and had slight lability, with a kcat of 0.00033 s(-1) for the Enterobacter cloacae enzyme. Its MICs for AmpC-derepressed E. cloacae and Citrobacter freundii were 4 to 8 microg/ml, compared with MICs of 0.12 to 2 microg/ml for AmpC-inducible and -basal strains; MICs for AmpC-derepressed Serratia marcescens and Morganella morganii were not raised. Cefixime and cefpodoxime were more labile than sanfetrinem to the E. cloacae AmpC enzyme, and AmpC-derepressed mutants showed much greater resistance; imipenem was more stable and retained full activity against derepressed mutants. Like imipenem, sanfetrinem was stable to TEM-1 and TEM-10 enzymes and retained full activity against isolates and transconjugants with various extended-spectrum TEM and SHV enzymes, whereas these organisms were resistant to cefixime and cefpodoxime. Sanfetrinem, like imipenem and cefixime but unlike cefpodoxime, also retained activity against Proteus vulgaris and Klebsiella oxytoca strains that hyperproduced potent chromosomal class A beta-lactamases. Functional group 2f enzymes, including Sme-1, NMC-A, and an unnamed enzyme from Acinetobacter spp., increased the sanfetrinem MICs by up to 64-fold. These enzymes also compromised the activities of imipenem and amoxicillin but not those of the cephalosporins. The hydrolysis of sanfetrinem was examined with a purified Sme-1 enzyme, and biphasic kinetics were found. Finally, zinc beta-lactamases, including IMP-1 and the L1 enzyme of Stenotrophomonas maltophilia, conferred resistance to sanfetrinem and all other beta-lactams tested, and hydrolysis was confirmed with the IMP-1 enzyme. We conclude that sanfetrinem has beta-lactamase interactions similar to those of the available carbapenems except that it is a weaker inducer of AmpC types, with some tendency to select derepressed mutants, unlike imipenem and meropenem.

Anti-Bacterial Agents↗
PubMed1998

Beta-lactamase inhibitors: agents to overcome bacterial resistance.

The extensive use of beta-lactam antibiotics in hospitals and community has created major resistance problems leading to increased morbidity, mortality and health-care costs. Resistance is most often mediated by -lactamases, which have emerged in both gram-positive and gram-negative bacteria. A novel approach to countering bacterial beta-lactamases is the delivery of a beta-lactam antibiotic in combination with a beta-lactamase inhibitor. Several such combinations are currently available, containing inhibitors clavulanic acid, sulbactam and tazobactam. These inhibitors are not, however, active against all beta-lactamases and the AmpC chromosomal enzymes that are hyperproduced by some enterobacteria and pseudomonas are a particular gap. Moreover, genes for these AmpC enzymes have begun to escape to plasmids. Consequently, there is a growing need for new broad-spectrum beta-lactamase inhibitors. This review offers an overview of synthetic beta-lactamase inhibitors, emphasizing information on their structures, and highlighting their activity against various beta-lactamases, particularly AmpC enzymes. Effective inhibition of AmpC enzymes are to be found among the penems and monobactams, but none of these has yet proved suitable for pharmaceutical development.

Animals↗
PubMed1997

pH effects on the inhibition of extended-spectrum and classical TEM beta-lactamases by penicillanic acid sulphones.

MICs of piperacillin with tazobactam or sulbactam (4 mg/L) were higher at pH 6.5 than at pH 8.0 for Escherichia coli transconjugants with TEM-1 or TEM-2 enzymes, but not for those with TEM-3 or TEM-10 enzymes. Investigation showed: (i) all four enzymes were less sensitive to sulphones at pH 6.5 than at pH 8.0; (ii) pH effects on MICs arose also for the TEM-3 and TEM-10 producers at lower sulphone concentrations; (iii) the TEM-3 and TEM-10 producers formed less enzyme than those with TEM-1 and TEM-2 and (iv) pH effects on the MICs for TEM-1 producers depended on enzyme quantity. We conclude that all four TEM enzymes have pH-dependent susceptibility to sulphones, but whether this affects MICs depends on the inhibitor:enzyme ratio achieved in the bacteria.

Anti-Bacterial Agents↗
PubMed1997

Sensitivity testing of ciprofloxacin for Pseudomonas aeruginosa.

UK clinical laboratories overestimate ciprofloxacin resistance amongst Pseudomonas aeruginosa isolates, relative to the MIC breakpoint of 1 mg/L. Most tests leading to this overestimation use 1 microg discs and are by Stokes' method with the breakpoint taken as the zone radius for P. aeruginosa NCTC 10662 minus 3 mm. Aiming to reduce this error rate, we examined alternative disc breakpoints. Tests were performed for 100 P. aeruginosa isolates on three media, with breakpoints selected (i) as the zone for P. aeruginosa NCTC 10662 minus 7 mm, as recommended for ciprofloxacin by the BSAC; (ii) with reference to MIC/zone correlation lines; (iii) from natural divisions in zone distribution histograms; and (iv) so as to minimize categorization errors. Breakpoints from regression lines, and those optimized to the susceptibility distribution, reduced the proportion of susceptible organisms misreported as resistant, but the improvement was not significant (P > 0.05, chi2 test). The breakpoint of the zone radius for P. aeruginosa NCTC 10662 minus 7 mm significantly reduced (P < 0.05) the number of susceptible organisms reported as resistant, but led to 50-75% of those with low level resistance (MIC 2-4 mg/L) and 4-10% of those with high-level resistance (MIC > 4 mg/L) being classed as susceptible. Irrespective of the medium and the basis of choosing breakpoints, 5 microg ciprofloxacin discs gave a lower rate of susceptible organisms being reported as resistant than did 1 microg discs; however, the improvement was not significant (P > 0.05, chi2 test) and the 5 microg discs had the disadvantages of forming very large zones for susceptible isolates and giving some--albeit small--zones for highly resistant organisms. In conclusion, the over-reporting of resistance could be reduced by use of zone breakpoints optimized to the MIC distribution and by the use of 5 microg discs, but the case for these changes is not overwhelming; taking the breakpoint as the zone for NCTC 10662 minus 7 mm led to unacceptable numbers of resistant organisms being reported as susceptible. More fundamentally, ciprofloxacin zones and MICs are continuously distributed for P. aeruginosa isolates, so susceptibility tests cannot divide the species into discrete populations. In these circumstances, it is optimistic to expect disc and MIC categorizations to agree perfectly.

Ciprofloxacin↗
PubMed1997

Potentiation of beta-lactams against Pseudomonas aeruginosa strains by Ro 48-1256, a bridged monobactam inhibitor of AmpC beta-lactamases.

Ro 48-1256 is a bridged monobactam inhibitor of Class C beta-lactamases, without significant antibacterial activity of its own. It was tested in combination with imipenem, meropenem, piperacillin and ceftazidime against Pseudomonas aeruginosa isolates, mutants and transconjugants. Imipenem was potentiated against all strains where the AmpC enzyme was inducible or derepressed, with its MICs being reduced from 1-2 mg/L to 0.25-0.5 mg/L for most isolates and from 8-16 mg/L to 1-2 mg/L for those lacking OprD (D2 porin). Ro 48-1256 also abolished in-vitro selection of OprD-deficient mutants by imipenem. Ceftazidime and piperacillin were potentiated against strains derepressed for AmpC enzyme, but not against those where the enzyme remained inducible. For over 90% of AmpC-derepressed organisms, the MICs of ceftazidime were reduced to < or = 8 mg/L by Ro 48-1256 (4 mg/L) and those of piperacillin were reduced to < or = 16 mg/L. Meropenem, which is very stable to AmpC, was not potentiated. Ro 48-1256 did not potentiate piperacillin, ceftazidime or carbapenems when resistance was mediated by Class A, B or D enzymes. Tazobactam, tested as control, had opposite behaviour to Ro 48-1256, potentiating beta-lactams when resistance was due to Class A beta-lactamases but failing to reverse resistance mediated by AmpC. Ro 48-1256 could be used with imipenem to overcome resistance mediated by loss of OprD, or with ceftazidime or piperacillin to overcome derepression of AmpC.

Anti-Bacterial Agents↗
PubMed1997

Permeability to carbapenems of Proteus mirabilis mutants selected for resistance to imipenem or other beta-lactams.

An imipenem-resistant mutant of Proteus mirabilis lacked a 26 kDa outer membrane protein (OMP). It has previously been postulated that this protein is a porin, but the present mutant, which was cross-resistant to mecillinam but not to other beta-lactams, proved as permeable to carbapenems as its parent. A mecillinam-selected mutant had similar cross-resistance yet retained the 26 kDa OMP, confirming that this protein was not important to resistance. In contrast, cefoxitin-selected mutants retained the 26 kDa protein but had diminished expression of major 41 and 44 kDa OMPs and showed reduced uptake of carbapenems, although this promoted resistance only when a carbapenemase was also present. We conclude that the imipenem-selected mutant owed its resistance to some factor other than porin loss, probably to a lesion in penicillin-binding protein 2.

Amdinocillin↗
PubMed1997

Bases of variation in resistance to beta-lactams in Klebsiella oxytoca isolates hyperproducing K1 beta-lactamase.

Nineteen isolates of Klebsiella oxytoca were examined, representing 18 distinct strains. All were from a 1994 survey of resistance amongst klebsiellae in intensive care units in Europe, and all had reduced susceptibility, or were resistant, to cefuroxime, ceftriaxone and aztreonam, suggesting hyperproduction of the chromosomal K1 beta-lactamase. We sought to confirm this mechanism and to identify why the levels of resistance varied between isolates. Possible reasons for variation were differences in the quantity or subtype of the K1 enzyme or differences in this enzyme's interplay with permeability. Spectrophotometric assays showed that all 19 isolates had K1-like beta-lactamases and that these were present at > or = 15-fold higher levels than in beta-lactam-sensitive K. oxytoca isolates. Fourteen of the 19 isolates had the OXY-2 form of K1 enzyme, while the remaining five had the OXY-1 form, as determined by isoelectric focusing and PCR amplification. Most isolates with the OXY-2 enzyme were more resistant than those with the OXY-1 subtype, but this difference partly reflected enzyme quantity rather than subtype. More generally, and irrespective of enzyme subtype, levels of resistance were broadly related to beta-lactamase specific activity, and the degree of hyperproduction was a major determinant of the level of resistance. Nevertheless, other factors had a role too: several isolates had reduced susceptibility or were resistant to cefoxitin, which is not a substrate for K1 enzyme, and examination of outer membrane protein profiles revealed considerable strain-to-strain diversity in the molecular weight range typical of the major enterobacterial porins (40-48 kDa).

Anti-Bacterial Agents↗
PubMed1997

OXA-15, an extended-spectrum variant of OXA-2 beta-lactamase, isolated from a Pseudomonas aeruginosa strain.

Pseudomonas aeruginosa AH, isolated in Ankara, Turkey, was highly resistant to ceftazidime (MIC, 128 microg/ml) and produced a beta-lactamase that gave a doublet of bands at pIs 8.7 and 8.9. beta-Lactamase production was transferable to P. aeruginosa PU21 by conjugation and was determined by a ca. 450-kb plasmid, pMLH54. The transconjugant and Escherichia coli transformed with the cloned gene showed increased resistance to ceftazidime (especially) and to cefpirome, ceftazidime, ceftriaxone, moxalactam, and aztreonam, but not to carbapenems. Resistance was not reversed by clavulanic acid or tazobactam. Sequencing revealed that the beta-lactamase responsible for this resistance was identical to OXA-2 except that glycine replaced aspartate at position 150. Compared to OXA-2, the new enzyme, named OXA-15, had greater cephalosporinase activity, with increased relative hydrolysis rates for cephaloridine and cephalothin and, most dramatically, for ceftazidime. Cefotaxime and carbapenems remained stable to hydrolysis. Thus, as in the TEM, SHV, and OXA-10 (PSE-2) beta-lactamase families, a minor sequence change in OXA-2 gave a major extension of cephalosporinase activity and contingent resistance. The gene encoding the new beta-lactamase, bla(OXA-15), lay close to the highly conserved 3' end of an integron and had flanking sequences typical of an integron-associated gene cassette. Restriction mapping and partial sequence data indicated that pMLH54 carries an integron with three putative gene cassettes: bla(OXA-15) itself, aadB [coding aminoglycoside nucleotidyltransferase (2")-1a], and an uncharacterized cassette.

Amino Acid Sequence↗
PubMed1996

Antibiotic resistance and production of extended-spectrum beta-lactamases amongst Klebsiella spp. from intensive care units in Europe.

Consecutive klebsiellae were collected from ICU patients at 35 centres in Western and Southern Europe. Of 966 isolates obtained, 716 were Klebsiella pneumoniae, 248 were Klebsiella oxytoca and two were Klebsiella ozaenae. Most were from Belgium, France, Germany, Holland, Italy, Portugal, Spain, Turkey and a few from Greece and the UK. Production of extended-spectrum beta-lactamases (ESBLs) was inferred in 220 isolates on the basis of synergy between ceftazidime and clavulanate. Putative ESBL producers were received from 23 centres, including 20 of the 27 that contributed more than 10 klebsiellae. Over 88% of putative ESBL producers were resistant to ceftazidime 2 mg/L, ceftriaxone 1 mg/L and aztreonam 1 mg/L, whereas, amongst ESBL-negative isolates, more than 98% of K. pneumoniae and 87% of K. oxytoca were susceptible to these concentrations. Putative ESBL producers wre also more resistant to cefuroxime and cefoxitin than non-producers, but not to biapenem. MIC distributions of ciprofloxacin, piperacillin/tazobactam and aminoglycosides were bimodal for ESBL producers, with some isolates highly sensitive and others very resistant. For example, 70% of putative ESBL producers were susceptible to piperacillin/tazobactam 16 + 4 mg/L, but 30% were resistant, some highly so. Resistance to this combination, and to ciprofloxacin, was clustered in certain centres. Two other groups of cephalosporin-resistant isolates were identified besides ESBL producers, viz. (i) nine isolates, from three centres, with AmpC beta-lactamases and (ii) 20 K. oxytoca, from 15 centres, that hyperproduced K1 enzyme. Examination of the hospitals' own susceptibility data indicated that up to 33% of putative ESBL producers had been reported susceptible to third-generation cephalosporins or monobactams. This is disturbing, since ESBLs have been associated with clinical failure even when only low-level resistance was apparent in vitro.

Ampicillin↗
PubMed1996

Type characterisation and antibiotic susceptibility of Burkholderia (Pseudomonas) cepacia isolates from patients with cystic fibrosis in the United Kingdom and the Republic of Ireland.

The spread of Burkholderia cepacia among cystic fibrosis (CF) patients in the UK prompted an investigation into whether an epidemic strain was responsible. A total of 366 B. cepacia isolates from 178 CF patients in 17 centres was examined by ribotyping and pulsed-field gel electrophoresis (PFGE). Associations were also sought between antibiotic resistance and strain type. More than 50 ribotype patterns were found but one, termed ribotype 1, was identified from 68 patients in eight centres. One centre had a single patient with this type while, in others, most or all patients harboured this organism. Small clusters of apparent cross-colonisation within centres were also evident for some other ribotypes. PFGE confirmed that ribotype 1 isolates were genetically similar. Ribotype 1 isolates were not markedly more resistant to antimicrobial agents than were other isolates, and the MICs of individual antibiotics were no more tightly clustered for ribotype 1 isolates than for others. Most isolates were resistant to ciprofloxacin, amikacin, gentamicin, tobramycin, carbenicillin, cefuroxime, cefotaxime, imipenem, biapenem, chloramphenicol, tetracycline, trimethoprim and sulphamethoxazole, but > or = 77% were susceptible to ceftazidime, piperacillin, piperacillin/ tazobactam and meropenem. We conclude that numerous strains of B. cepacia colonise CF patients in the UK and Ireland but that one epidemic strain has spread in at least eight centres. Isolates of this strain appear homogenous in total genomic profile but very variable in antibiotic susceptibility.

Bacterial Typing Techniques↗
PubMed1996

Are all beta-lactams created equal?

beta-Lactams are the largest antibiotic family, but are readily compromised by resistance. The result has been a cat-and-mouse game between chemists and bacteria, with the compounds repeatedly modified to overcome emergent resistance. With penicillins, it is possible to obtain spectrum, or beta-lactamase stability, but difficult to combine both. In general, it is better to protect a labile penicillin with an inhibitor, though this strategy is limited by the absence of good inhibitors of AmpC beta-lactamases. Combining spectrum and beta-lactamase stability proved easier with cephalosporins, but it is difficult to cover enterobacteria, anaerobes, non-fermenters and staphylococci with a single compound, and enterococci are consistently resistant. Carbapenems allow the broadest spectrum of available beta-lactams. Less equal or predictable than initial spectrum is how rapidly resistance emerges. This point is especially important pertinent to beta-lactamases; PBP changes compromise all beta-lactams. Spread of plasmidic beta-lactamases destroyed the utility of penicillin G against staphylococci and that of anti-gram-negative penicillins against enterobacteria. Resistance to 'beta-lactamase-stable' cephalosporins has recently spread in enterobacteria, mediated by hyperproduction of AmpC beta-lactamases and extended-spectrum TEM and SHV types. Carbapenems were launched shortly after 3rd-generation cephalosporins, but beta-lactamase-mediated resistance has emerged more slowly. Nevertheless, recent reports of zinc carbapenems in gram-negative bacteria from Japan are disturbing.

Anti-Bacterial Agents↗
PubMed1995

Bacterial resistance to carbapenems.

The carbapenems have the broadest spectra of all beta-lactams but resistance still occurs, caused by target modification, impermeability or beta-lactamase production. Target modification or replacement is important in methicillin-resistant staphylococci, E. faecium and some pneumococci. These organisms present the greatest current threat to carbapenem efficacy. Impermeability to carbapenems arises in P. aeruginosa mutants, where it is contingent on loss of D2 outer membrane protein, a minor porin. This resistance functions only if the Pseudomonas retains its chromosomal group 1 beta-lactamase, and so reflects the interplay of impermeability and hydrolysis rather than impermeability alone; nevertheless porin loss is the critical change that engenders resistance. Resistance based on impermeability coupled to a group 1 beta-lactamase has also been described in E. cloacae, but demands loss of a major porin and is much rarer and less stable than in P. aeruginosa. Although group 1 beta-lactamases contribute to resistance in these organisms, they have only feeble carbapenemase activity. Chromosomal beta-lactamases with potent carbapenemase activity occur in most or all X. maltophilia, A. hydrophila and F. odoratum isolates. These enzymes, which cause carbapenem resistance when expressed copiously, are all zinc-dependent. Zinc carbapenemases also are a concern in B. fragilis, where they are encoded by the chromosomal DNA of c. 3% of isolates, though expressed by only 1%. Carbapenemases are extremely rare outside these species. Nevertheless, a plasmidic zinc carbapenemase was reported from one P. aeruginosa isolate and from several S. marcescens. Further carbapenemases, some not zinc-dependent, are known from a tiny numbers of Serratia, Enterobacter, and Acinetobacter isolates. Despite these various modes of resistance, carbapenems have retained their efficacy far better than have expanded-spectrum cephalosporins. Whether this advantage will be retained indefinitely is uncertain. If resistance does become more prevalent it may be possible to derivatize the carbapenems so as to extend their activity. There is already interest in the design of carbapenems that bind beta-lactam-resistant PBPs and, to an extent, in the development of carbapenemase inhibitors.

Bacteria↗
PubMed1995

Transferable production of PER-1 beta-lactamase in Pseudomonas aeruginosa.

PER-1, an extended-spectrum class A beta-lactamase, has been described only from Pseudomonas aeruginosa RNL-1, which was obtained in France in 1991. During studies on ceftazidime-resistant P. aeruginosa collected from December 1991 to July 1993 in Ankara, Turkey, we found 14 further isolates with PER-1 enzyme, as recognised by isoelectric point (pI 5.4), hydrolytic activity, gene hybridization and DNA sequence. Five of these isolates also had OXA-10 (PSE-2)-related enzymes and one hyper-produced ampC beta-lactamase, whereas eight had PER-1 enzyme alone. The last group, from four wards, appeared to be identical, giving the same DNA restriction patterns and carrying the PER-1 gene on an 8.5 kb HincII fragment. Two more producers were related but the other four were unique. In several representatives of the group of eight replicates, the PER-1 gene was shown to be encoded on a plasmid, larger than 154 kb in size, which transferred to P. aeruginosa PU21. A further isolate had the gene on an even larger conjugative plasmid. By contrast, the PER-1 gene reportedly was chromosomally-inserted in strain RNL-1. The PER-1 producers and their transconjugants were highly resistant to ceftazidime and aztreonam (MIC > or = 128 mg/L) but not to carbapenems or latamoxet. Piperacillin insusceptibility was marginal (MIC 8 mg/L). Clavulanate 4 mg/L, but not tazobactam 4 mg/L, reversed resistance to ceftazidime and carbenicillin. Purification of the enzyme to homogeneity was achieved by three ion exchanges and one gel filtration. We found much lower Vmax rates for aminothiazolyl cephalosporins than reported previously for PER-1 enzyme. This reflected the present assays being in 0.1 M phosphate buffer pH 7.0, whereas the previous were pH-stat-regulated; concentrated phosphate reduced enzyme activity against ceftazidime, but not against cephaloridine.

Base Sequence↗
PubMed1995

National survey of susceptibility to antimicrobials amongst clinical isolates of Pseudomonas aeruginosa.

Between September and December 1993, each of 24 hospitals in the UK collected up to 100 consecutive clinical isolates of Pseudomonas aeruginosa and sent these to the London Hospital Medical College (LHMC). Of 2184 cultures received, 1991 contained viable P. aeruginosa. Minimum inhibitory concentrations (MICs) of antimicrobials were determined by agar dilution. The frequencies of resistance to low breakpoints were as follows: gentamicin, MIC > 2 mg/L, 11.7%; amikacin, MIC > 4 mg/L, 10.5%, carbenicillin, MIC > 128 mg/L, 11.7%; azlocillin, MIC> 16 mg/L, 10.9%; ceftazidime, MIC > 4 mg/L, 9.6%; ciprofloxacin, MIC > 1 mg/L, 8.1%; imipenem, MIC > 4 mg/L 2.5% and meropenem, MIC > 4 mg/L, 1.1%. Resistance to each antimicrobial except amikacin was commoner among the 134 isolates from patients in intensive care units (ICUs) than amongst the 1042 isolates from other in-patients (P < 0.01). Resistance to penicillins and ceftazidime, though not to other agents, was rarer among the 797 isolates from out-patients than amongst those from non-ICU in-patient (P < 0.01). Compared to a similar study in 1982, during which 1866 isolates had been examined, the frequency of resistance to the aminoglycosides increased (P < 0.05) as had those to the penicillins and ceftazidime (P < 0.01). Ciprofloxacin and the carbapenems were not tested in 1982. Cross-resistance patterns suggested that the increases in resistance to aminoglycosides and beta-lactams were largely a reflection of greater numbers of isolates with barrier or efflux mechanisms and were not due to an increase in isolates with antibiotic-degrading enzymes. The participating hospitals mostly employed Stokes' disc diffusion method and, when the results were compared to the MICs determined at the LHMC, fewer than 9% of the isolates reported as susceptible were found to be resistant. However, up to 72% of those reported by the hospitals as resistant were found to be susceptible.

Anti-Bacterial Agents↗