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Morphological changes and lysis induced by beta-lactams associated with the characteristic profiles of affinities of penicillin-binding proteins in actinobacillus pleuropneumoniae.

Actinobacillus pleuropneumoniae, which was formerly classified in the genus Haemophilus, is a pathogen causing swine pleuropneumonia. We found that aspoxicillin showed strong activity and that meropenem had better lytic activity against this pathogen. In the present study, we for the first time identified penicillin-binding proteins (PBPs) of A. pleuropneumoniae in order to elucidate the relationship between the antibacterial and lytic activities of beta-lactam antibiotics and affinities of the PBPs. The competitive assay using (3)H-labeled benzylpenicillin revealed seven PBPs in A. pleuropneumoniae; they were determined to be PBPs 1a, 1b, 2, 3, 4, 5, and 6, and the molecular masses of these PBPs were estimated to be 92, 80, 76, 72, 50, 44, and 30 kDa, respectively, by comparison with those of Haemophilus influenzae. Our detailed analysis of the affinities of the PBPs of A. pleuropneumoniae and of the bacterial lysis kinetics for several beta-lactam antibiotics revealed that the strong antibacterial activity of aspoxicillin against this strain could be related to the higher affinity of PBP 3 and that preferential inactivation of PBP 1b could cause rapid lysis.

Actinobacillus pleuropneumoniae↗

The Legionella (Fluoribacter) gormanii metallo-beta-lactamase: a new member of the highly divergent lineage of molecular-subclass B3 beta-lactamases.

A metallo-beta-lactamase determinant was cloned from a genomic library of Legionella (Fluoribacter) gormanii ATCC 33297(T) constructed in the plasmid vector pACYC184 and transformed into Escherichia coli DH5alpha, by screening for clones showing a reduced susceptibility to imipenem. The product of the cloned determinant, named FEZ-1, contains a 30-kDa polypeptide and exhibits an isoelectric pH of 7.6. Sequencing revealed that FEZ-1 is a molecular-class B beta-lactamase which shares the closest structural similarity (29.7% of identical residues) with the L1 enzyme of Stenotrophomonas maltophilia, being a new member of the highly divergent subclass B3 lineage. All the residues that in L1 are known to be directly or indirectly involved in coordination of the zinc ions were found to be conserved also in FEZ-1, suggesting that the geometry of zinc coordination in the active site of the latter enzyme is identical to that of L1. Unlike L1, however, FEZ-1 appeared to be monomeric in gel permeation chromatography experiments and exhibited a distinctive substrate specificity with a marked preference for cephalosporins and meropenem. The properties of FEZ-1 overall resembled those of a beta-lactamase previously purified from the same strain of L. gormanii (T. Fujii, K. Sato, K. Miyata, M. Inoue, and S. Mitsuhashi, Antimicrob. Agents Chemother. 29:925-926, 1986) and are as yet unique among class B enzymes, reinforcing the notion that considerable functional heterogeneity can be encountered among members of this class. A system for overexpression of the bla(FEZ-1) gene in E. coli, based on the T7 phage promoter, was also developed.

Amino Acid Sequence↗

Molecular and biochemical heterogeneity of class B carbapenem-hydrolyzing beta-lactamases in Chryseobacterium meningosepticum.

Although the carbapenem-hydrolyzing beta-lactamase (CHbetaL) BlaB-1 is known to be in Chryseobacterium meningosepticum NCTC 10585, a second CHbetaL gene, bla(GOB-1), was cloned from another C. meningosepticum clinical isolate (PINT). The G+C content of bla(GOB-1) (36%) indicated the likely chromosomal origin of this gene. Its expression in Escherichia coli DH10B yields a mature CHbetaL with a pI of 8.7 and a relative molecular mass of 28.2 kDa. In E. coli, GOB-1 conferred resistance to narrow-spectrum cephalosporins and reduced susceptibility to ureidopenicillins, broad-spectrum cephalosporins, and carbapenems. GOB-1 had a broad-spectrum hydrolysis profile including penicillins and cephalosporins (but not aztreonam). The catalytic efficiency for meropenem was higher than for imipenem. GOB-1 had low amino acid identity with the class B CHbetaLs, sharing 18% with the closest, L-1 from Stenotrophomonas maltophilia, and only 11% with BlaB-1. Most of the conserved amino acids that may be involved in the active site of CHbetaLs (His-101, Asp-103, His-162, and His-225) were identified in GOB-1. Sequence heterogeneity was found for GOB-1-like and BlaB-1-like beta-lactamases, having 90 to 100% and 86 to 100% amino acid identity, respectively, among 10 unrelated C. meningosepticum isolates. Each isolate had a GOB-1-like and a BlaB-1-like gene. The same combination of GOB-1-like and BlaB-1-like beta-lactamases was not found in two different isolates. C. meningosepticum is a bacterial species with two types of unrelated chromosome-borne class B CHbetaLs that can be expressed in E. coli and, thus, may represent a clinical threat if spread in gram-negative aerobes.

Amino Acid Sequence↗

Antimicrobial susceptibility and clinical sources of Dolosigranulum pigrum cultures.

Antimicrobial susceptibilities of 27 clinical isolates of Dolosigranulum pigrum were determined. All were susceptible to amoxicillin, cefotaxime, cefuroxime, clindamycin, levofloxacin, meropenem, penicillin, quinupristin-dalfopristin, rifampin, tetracycline, and vancomycin. Fifteen of the isolates were intermediate to chloramphenicol. One isolate was resistant to trimethoprim-sulfamethoxazole. Two isolates were susceptible, 10 were intermediate, and 15 were resistant to erythromycin.

Adult↗

In vitro activities of MK-826 (L-749,345) against 363 strains of anaerobic bacteria.

The activity of MK-826 was compared to the activities of cefoxitin, ceftriaxone, imipenem, and meropenem against 363 gram-negative and gram-positive anaerobes by using NCCLS procedures. At least 98% of the strains were susceptible to the carbapenems. All strains of Clostridium perfringens, Fusobacterium nucleatum, Peptostreptococcus, and Sutterella wadsworthensis were susceptible to all agents tested.

Anti-Bacterial Agents↗

Cefepime, piperacillin-tazobactam, and the inoculum effect in tests with extended-spectrum beta-lactamase-producing Enterobacteriaceae.

There is little information about the clinical effectiveness of cefepime and piperacillin-tazobactam in the treatment of infections caused by extended-spectrum beta-lactamase (ESBL)-producing pathogens. Some inferences have been drawn from laboratory studies, which have usually involved only one or a few strains of ESBL-producing Klebsiella pneumoniae or Escherichia coli that produced only a limited range of ESBLs. Such studies are indirect, sometimes conflicting, indicators of efficacy. To extend previous laboratory findings, a study was designed to investigate organism-drug interactions by determining the in vitro activities of eight parenteral beta-lactam agents against 82 clinical and laboratory strains of Klebsiella, Escherichia, Enterobacter, Citrobacter, Serratia, Morganella, and Proteus species that produced 22 different ESBLs, alone or in combination with other beta-lactamases. Activities were determined in broth microdilution MIC tests using standard and 100-fold-higher inocula. An inoculum effect, defined as an eightfold or greater MIC increase on testing with the higher inoculum, was most consistently detected with cefepime, cefotaxime, and ceftriaxone and least frequently detected with meropenem and cefoteten. Piperacillin-tazobactam was intermediate between these two groups of agents. Although the inoculum effect is an in vitro laboratory phenomenon, if it has any predictive value in identifying increased risk of therapeutic failure in serious infections, these results support suggestions that cefepime may be a less-than-reliable agent for therapy of infections caused by ESBL-producing strains.

Anti-Bacterial Agents↗

Characterization of OXA-25, OXA-26, and OXA-27, molecular class D beta-lactamases associated with carbapenem resistance in clinical isolates of Acinetobacter baumannii.

Carbapenem resistance in Acinetobacter spp. is increasingly being associated with OXA-type beta-lactamases with weak hydrolytic activity against imipenem and meropenem. Such enzymes were characterized from Acinetobacter isolates collected in Belgium, Kuwait, Singapore, and Spain. The isolates from Spain and Belgium had novel class D beta-lactamases that were active against carbapenems. These were designated OXA-25 and OXA-26, respectively, and had >98% amino acid homology with each other and with the OXA-24 enzyme recently described by others from an Acinetobacter isolate collected elsewhere in Spain. The isolate from Singapore had OXA-27 beta-lactamase, another novel class D type with only 60% homology to OXA-24, -25, and -26, but with 99% homology to OXA-23 (ARI-1), described previously from an Acinetobacter baumannii isolate collected in Scotland. Sequence data were not obtained for the carbapenem-hydrolyzing OXA enzyme from the isolate from Kuwait; nevertheless, the enzyme was phenotypically similar to OXA-25 and -26. The enzymes OXA-23, -24, -25, -26, and -27 retained the STFK and SXV motifs typical of class D beta-lactamases, but the YGN motif was altered to FGN. The KTG motif was retained by OXA-27 and -23 but was replaced by KSG in OXA-24, -25, and -26. OXA-25 and -26 enzymes were strongly active against oxacillin, but unusually for an OXA-type beta-lactamase, OXA-27 had apparently weak activity, although measurement was complicated by biphasic kinetics. None of the new enzymes was transmissible to Escherichia coli recipients. Many Acinetobacter isolates are multiresistant to other antibiotics, and the emergence of class D enzymes with carbapenem-hydrolyzing activity is a disturbing development for antimicrobial chemotherapy.

Acinetobacter↗

In vitro and in vivo properties of Ro 63-9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci.

Ro 63-9141 is a new member of the pyrrolidinone-3-ylidenemethyl cephem series of cephalosporins. Its antibacterial spectrum was evaluated against significant gram-positive and gram-negative pathogens in comparison with those of reference drugs, including cefotaxime, cefepime, meropenem, and ciprofloxacin. Ro 63-9141 showed high antibacterial in vitro activity against gram-positive bacteria except ampicillin-resistant enterococci, particularly vancomycin-resistant strains of Enterococcus faecium. Its MIC at which 90% of the isolates tested were inhibited (MIC(90)) for methicillin-resistant Staphylococcus aureus (MRSA) was 4 microg/ml. Ro 63-9141 was bactericidal against MRSA. Development of resistance to the new compound in MRSA was not observed. Ro 63-9141 was more potent than cefotaxime against penicillin-resistant Streptococcus pneumoniae (MIC(90) = 2 microg/ml). It was active against ceftazidime-susceptible strains of Pseudomonas aeruginosa and against Enterobacteriaceae except Proteus vulgaris and some isolates producing extended-spectrum beta-lactamases. The basis for the antibacterial spectrum of Ro 63-9141 lies in its affinity to essential penicillin-binding proteins, including PBP 2' of MRSA, and its stability towards beta-lactamases. The in vivo findings were in accordance with the in vitro susceptibilities of the pathogens. These data suggest the potential utility of Ro 63-9141 for the therapy of infections caused by susceptible pathogens, including MRSA. Since insufficient solubility of Ro 63-9141 itself precludes parenteral administration in humans, a water-soluble prodrug, Ro 65-5788, is considered for development.

Abscess↗

Association of amino acid substitutions in penicillin-binding protein 3 with beta-lactam resistance in beta-lactamase-negative ampicillin-resistant Haemophilus influenzae.

The affinity of [(3)H]benzylpenicillin for penicillin-binding protein (PBP) 3A was reduced in 25 clinical isolates of beta-lactamase-negative ampicillin (AMP)-resistant (BLNAR) Haemophilus influenzae for which the AMP MIC was > or =1.0 microg/ml. The affinities of PBP 3B and PBP 4 were also reduced in some strains. The sequences of the ftsI gene encoding the transpeptidase domain of PBP 3A and/or PBP 3B and of the dacB gene encoding PBP 4 were determined for these strains and compared to those of AMP-susceptible Rd strains. The BLNAR strains were classified into three groups on the basis of deduced amino acid substitutions in the ftsI gene, which is thought to be involved in septal peptidoglycan synthesis. His-517, near the conserved Lys-Thr-Gly (KTG) motif, was substituted for Arg-517 in group I strains (n = 9), and Lys-526 was substituted for Asn-526 in group II strains (n = 12). In group III strains (n = 4), three residues (Met-377, Ser-385, and Leu-389), positioned near the conserved Ser-Ser-Asn (SSN) motif, were replaced with Ile, Thr, and Phe, respectively, in addition to the replacement with Lys-526. The MICs of cephem antibiotics with relatively high affinities for PBP 3A and PBP 3B were higher than those of AMP and meropenem for group III strains. The MICs of beta-lactams for H. influenzae transformants into which the ftsI gene from BLNAR strains was introduced were as high as those for the donors, and PBP 3A and PBP 3B showed decreased affinities for beta-lactams. There was no clear relationship between 7-bp deletions in the dacB gene and AMP susceptibility. Even though mutations in another gene(s) may be involved in beta-lactam resistance, these data indicate that mutations in the ftsI gene are the most important for development of resistance to beta-lactams in BLNAR strains.

Ampicillin↗

Antipneumococcal activity of ertapenem (MK-0826) compared to those of other agents.

The activities of ertapenem (MK-0826) and eight other agents against a range of penicillin-susceptible and -resistant pneumococci were tested by determination of MICs by the microdilution method and by the time-kill methodology. For 125 penicillin-susceptible, 74 penicillin-intermediate, and 86 penicillin-resistant pneumococci, the MICs at which 50% of isolates are inhibited (MIC(50)s) and MIC(90)s, as determined by the microdilution method, were as follows: for ertapenem, 0.016 and 0.03, 0.125 and 0.5, and 0.5 and 1.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for amoxicillin, < or =0.016 and 0.03, 0.25 and 1.0, and 2.0 and 2.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for cefprozil, 0.125 and 0.25, 1.0 and 8.0, and 16.0 and 16.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for cefepime, < or =0.016 and 0.06, 0.5 and 1.0, and 1.0 and 2.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for ceftriaxone, < or =0.016 and 0.06, 0.25 and 1.0, and 1.0 and 2.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for imipenem, < or =0.008 and < or =0.008, 0.03 and 0.25, and 0.25 and 0.25 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for meropenem, < or =0.008 and 0.016, 0.125 and 0.5, and 0.5 and 1.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; and for clarithromycin, 1.0 and >32.0, 1.0 and >32.0, and >32.0 and >32.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively. For 64 strains for which quinolone MICs were increased (ciprofloxacin MICs, > or =4.0 microg/ml), the MIC(90) of ertapenem was 1.0 microg/ml and the MIC(90)s of the other beta-lactams tested and clarithromycin were >32.0 microg/ml. Against four penicillin-susceptible, four penicillin-intermediate, and four penicillin-resistant strains, testing by the time-kill methodology showed that ertapenem at two times the MIC was bacteriostatic (99% killing) after 12 h and bactericidal (99.9% killing) against all strains by 24 h, with 90% killing of all strains at two times the MIC after 6 h. At the MIC, ertapenem was bacteriostatic against all strains tested after 24 h. Although the bactericidal activity of imipenem at the MIC after 24 h was significantly greater than that of ertapenem, the kinetics of the two drugs at two times the MIC were similar after 24 h. The killing kinetics of clarithromycin were slower than those of ertapenem and other agents, with clarithromycin at two times the MIC having bactericidal activity against seven of eight macrolide-susceptible strains after 24 h.

Amoxicillin↗

EBR-1, a novel Ambler subclass B1 beta-lactamase from Empedobacter brevis.

Empedobacter brevis (formerly designated Flavobacterium breve) is a gram-negative aerobe involved in nosocomial infections. The Ambler class B beta-lactamase gene bla(EBR-1) was cloned and expressed in Escherichia coli from E. brevis clinical strain ASS-1, which had reduced susceptibility to expanded-spectrum cephalosporins and carbapenems. Purified beta-lactamase EBR-1 hydrolyzed penicillins, cephalosporins, and carbapenems efficiently but not aztreonam. Kinetic parameters of EBR-1 were similar to those of class B enzymes such as BlaB, IND-2, and GOB-1 identified from other Flavobacteriaceae species, except for meropenem, which was more hydrolyzed by beta-lactamase GOB-1. EBR-1, with a pI of 8.0 and a relative molecular mass of ca. 25 kDa, was classified in functional subgroup 3a, which includes most of the class B beta-lactamases. EBR-1, which belongs to molecular subclass B1 of metalloenzymes, shares 58, 57, and 42% amino acid identity with the most closely related beta-lactamases, IND-1/IND-2 from Chryseobacterium indologenes, CGB-1 from Chryseobacterium gleum, and BlaB from Chryseobacterium meningosepticum, respectively.

Amino Acid Sequence↗

Expression of SHV-2 beta-lactamase and of reduced amounts of OmpK36 porin in Klebsiella pneumoniae results in increased resistance to cephalosporins and carbapenems.

A Klebsiella pneumoniae clinical isolate was resistant to cefoxitin, cefotaxime, ceftazidime, ceftazidime-clavulanate, piperacillin-tazobactam (MICs, >256 micro g/ml in all cases), and meropenem (MIC, 16 micro g/ml) and was intermediate to imipenem (MIC, 8 micro g/ml). Decreased expression of the OmpK36 porin and expression of an SHV-2 beta-lactamase contributed to the observed resistance to these beta-lactam-containing agents.

Amino Acid Sequence↗

Epigallocatechin gallate synergistically enhances the activity of carbapenems against methicillin-resistant Staphylococcus aureus.

Combinations of carbapenems and epigallocatechin gallate (EGCg; a main constituent of tea catechins) showed potent synergy against 24 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). MICs of imipenem in the presence of EGCg at 3.125, 6.25, 12.5, and 25 microg/ml, were restored to the susceptible breakpoint (< or =4 microg/ml) for 8, 38, 46, and 75% of the MRSA isolates, respectively. Similar results were also observed for combinations of panipenem or meropenem and EGCg. Therefore, the combinations may be worthy of further evaluation in vivo against MRSA infection.

Antioxidants↗

High incidence of cefoxitin and clindamycin resistance among anaerobes in Taiwan.

Susceptibilities to 16 antimicrobial agents were determined by measurement of MICs for 344 isolates of anaerobic bacteria recovered from patients with significant infections. Resistance rates varied among antimicrobial agents and the species tested. The beta-lactams were more active in gram-positive than in gram-negative anaerobes. Resistance to meropenem was low (<1%). For beta-lactam-beta-lactamase inhibitors, piperacillin-tazobactam was most active for all species (resistance, <6%). The rates of resistance to cefoxitin (31 to 65%) and clindamycin (50 to 70%) for non-Bacteroides fragilis species of the B. fragilis group were higher than those for B. fragilis (4% resistant to cefoxitin and 33% resistant to clindamycin). Among members of B. fragilis group, Bacteroides thetaiotaomicron was the most resistant to clindamycin (70%) and cefoxitin (65%). Rates of susceptibility to imipenem and metronidazole for B. fragilis continue to be high compared to those from a previous study 10 years ago. However, resistance to metronidazole was found recently in five strains of B. fragilis. We analyzed the genetic relationships among the metronidazole-resistant B. fragilis strains by pulsed-field gel electrophoresis. The metronidazole-resistant B. fragilis strains showed genotypic heterogeneity, excluding the dissemination of a single clone.

Anti-Bacterial Agents↗

Role of Klebsiella pneumoniae OmpK35 porin in antimicrobial resistance.

OmpK35 from Klebsiella pneumoniae is the homologue of Escherichia coli OmpF porin. Expression of OmpK35 in K. pneumoniae strain CSUB10R (lacking both OmpK35 and OmpK36) decreased the MICs of cephalosporins and meropenem > or = 128-fold and decreased the MICs of imipenem, ciprofloxacin, and chloramphenicol > or = 8-fold. MIC reductions by OmpK35 were 4 times (cefepime), 8 times (cefotetan, cefotaxime, and cefpirome), or 128 times (ceftazidime) higher than those caused by OmpK36, but the MICs were similar or 1 dilution lower for other evaluated agents.

Amino Acid Sequence↗

Trends in antimicrobial susceptibilities among Enterobacteriaceae isolated from hospitalized patients in the United States from 1998 to 2001.

Longitudinal surveillance of Enterobacteriaceae for antimicrobial susceptibility is important because species of this family are among the most significant and prevalent human pathogens. To estimate rates of in vitro antimicrobial susceptibility among hospitalized patients in the United States, data from The Surveillance Network were studied for 14 agents tested against 10 species of Enterobacteriaceae (n = 384,279) isolated from intensive-care-unit (ICU) patients and non-ICU inpatients from 1998 to 2001. Cumulative susceptibility (percent) data for all species of Enterobacteriaceae isolated from ICU patients and non-ICU inpatients, respectively, were ranked as follows: ampicillin-sulbactam (45.5 and 57.2) << ticarcillin-clavulanate (74.8 and 83.5) < trimethoprim-sulfamethoxazole (87.0 and 84.5) congruent with cefotaxime (82.9 and 92.6) = ceftazidime (82.3 and 91.0) = ceftriaxone (86.5 and 93.9) = piperacillin-tazobactam (83.5 and 90.5) < levofloxacin (89.3 and 90.6) = ciprofloxacin (91.0 and 91.7) < gentamicin (91.8 and 94.3) < cefepime (95.0 and 97.9) < amikacin (98.5 and 99.2) < imipenem (100 and 100) = meropenem (100 and 100). Of those agents studied only susceptibilities to ciprofloxacin (94 to 89%) and levofloxacin (93 to 89%) decreased in a stepwise manner from 1998 to 2001. Decreased fluoroquinolone susceptibility was most pronounced for Escherichia coli, Proteus mirabilis, and Enterobacter cloacae. For all species of Enterobacteriaceae, trimethoprim-sulfamethoxazole resistance was more commonly observed in isolates with a single-drug resistance phenotype while gentamicin and fluoroquinolone resistances were more common in isolates resistant to at least one additional class of antimicrobial agent. Ongoing surveillance of Enterobacteriaceae will be particularly important to monitor changes in fluoroquinolone susceptibility, as well as changes in the prevalence of isolates resistant to multiple classes of antimicrobial agents.

Ampicillin↗

High prevalence of antimicrobial resistance in rapidly growing mycobacteria in Taiwan.

An increasing number of clinical isolations of rapidly growing mycobacteria (RGM) at the National Taiwan University Hospital were noted from 1992 to 2001. Broth microdilution MICs of 15 antimicrobial agents were determined for 200 clinical isolates of RGM, including the Mycobacterium fortuitum group (69 isolates), M. chelonae (39 isolates), and M. abscessus (92 isolates). Our results showed that the resistance rates of these isolates to the currently available agents were remarkably high. Amikacin was active against nearly all RGM isolates. Clarithromycin was usually active against M. abscessus (79% susceptibility) and the M. fortuitum group (65% susceptibility). The majority of M. fortuitum group isolates were susceptible to ciprofloxacin (62%) and imipenem (61%). The susceptibilities to other conventional anti-RGM agents of these isolates were poor but differed markedly by species. The newer fluoroquinolones (levofloxacin, moxifloxacin, and gatifloxacin) and meropenem showed better in vitro activities against the M. fortuitum group isolates than against the other two species of RGM. Linezolid had fairly good activity against these RGM isolates, particularly against M. chelonae isolates (82% susceptible). Telithromycin had poor activity against these RGM isolates (the MICs at which 50% of the isolates tested are inhibited [MIC(50)s] were 32 to 64 microg/ml, and the MIC(90)s were >64 microg/ml).

Anti-Bacterial Agents↗

Antimicrobial resistance of Campylobacter jejuni subsp. jejuni strains isolated from humans in 1998 to 2001 in Montréal, Canada.

The rates of resistance of 51 to 72 human strains of Campylobacter jejuni subsp. jejuni isolated annually from 1998 to 2001 in Montréal, Québec, Canada, varied from 1 to 12% for erythromycin, 43 to 68% for tetracycline, and 10 to 47% for ciprofloxacin. In the last years of the study, there was a significant increase in the rate of resistance to ciprofloxacin (P = 0.00003) but not in the rate of resistance to erythromycin (P = 0.056) or tetracycline (P = 0.095) compared to the rate obtained in the first years. All 51 C. jejuni strains isolated in 2001 were susceptible to gentamicin, amoxicillin-clavulanic acid, imipenem, and meropenem. From 1999 to 2001, 74 strains of C. jejuni acquired abroad were significantly more resistant to ciprofloxacin than 109 strains of C. jejuni acquired locally (66 versus 9%, P < 0.00001) but were not significantly more resistant to erythromycin (1 versus 6%, P = 0.15) or to tetracycline (55 versus 58%, P = 0.87).

Anti-Bacterial Agents↗