An association between reduced susceptibility to daptomycin and reduced susceptibility to vancomycin in Staphylococcus aureus.
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Anti-Bacterial Agents↗
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Correlation between alterations of the penicillin-binding protein 2 and modifications of the peptidoglycan structure in Neisseria meningitidis with reduced susceptibility to penicillin G.
Reduced susceptibility to penicillin G in Neisseria meningitidis is directly correlated with alterations in the penA gene, which encodes the penicillin-binding protein 2 (PBP2). Using purified PBP2s from different backgrounds, we confirmed that the reduced susceptibility to penicillin G is associated with a decreased affinity of altered PBP2s for penicillin G. Infrared spectroscopy analysis using isogenic penicillin-susceptible strains and strains with reduced susceptibility to penicillin G suggested that the meningococcal cell wall is also modified in a penA-dependent manner. Moreover, reverse-phase high pressure liquid chromatography and mass spectrometry analysis of these meningococcal strains confirmed the modifications of peptidoglycan components and showed an increase in the peaks corresponding to pentapeptide-containing muropeptides. These results suggest that the D,D-transpeptidase and/or D,D-carboxypeptidase activities of PBP2 are modified by the changes in penA gene.
Chromatography, High Pressure Liquid↗
Lineage structure and penicillin-binding protein variability in clinical Streptococcus pneumoniae isolates from Southwest China exhibiting reduced susceptibility to penicillin.
BACKGROUND: Reduced susceptibility to penicillin in Streptococcus pneumoniae is mediated primarily by alterations in penicillin-binding proteins (PBPs) and often coexists with multidrug resistance within successful lineages. The region-specific genomic characterization of clinically relevant pneumococci with reduced penicillin susceptibility in Southwest China remains limited. METHODS: We performed whole-genome sequencing of 204 clinical S. pneumoniae isolates collected from five institutions in Southwest China (2018-2022) that met our operational screening definition of reduced susceptibility to penicillin (PEN MIC ≥0.12 μg/mL). Molecular serotypes, MLST types, and Global Pneumococcal Sequence Clusters (GPSCs) were assigned; virulence and antimicrobial resistance determinants were profiled; and a core genome phylogeny was reconstructed with international contextualization through the use of PubMLST genomes meeting the same MIC criterion. Amino acid variability in PBP1a/PBP2b/PBP2x was quantified using TIGR4 numbering, and highly variable noncatalytic residues located within 15 Å of catalytic motifs were prioritized via structure-guided screening. RESULTS: The isolates showed a high burden of resistance to non-β-lactam antibiotics (erythromycin, 98.5%; tetracycline, 82.8%; trimethoprim-sulfamethoxazole, 64.7%), while fluoroquinolone susceptibility was largely preserved (≥97%), and vancomycin/linezolid resistance was not detected. Twenty-seven serotypes were identified, among which 19F (23.5%) and 19A (14.2%) were dominant, and the estimated PCV13 coverage was 69.6%. GPSC1 was the dominant lineage (36.8%), and the lineage composition among our isolates differed markedly from those in the PubMLST-USA and PubMLST-Thailand subsets. Virulence and resistance gene carriage differed markedly between GPSC1 and non-GPSC1 isolates, with enrichment of pilus operons, mef(A)/msr(D), and folA/folP in GPSC1. PBP variations were clustered in transpeptidase domains and motif-adjacent regions while essential catalytic residues were conserved; with the structure-guided filter, 12, 11, and 11 motif-proximal noncatalytic candidate sites were prioritized in PBP1a, PBP2b, and PBP2x, respectively. CONCLUSION: Clinical S. pneumoniae isolates with reduced penicillin susceptibility collected in Southwest China demonstrated resistance and accessory gene profiles that were strongly structured by a GPSC-defined lineage background. Our site-resolved, structure-guided PBP analysis provides a regional PBP variability landscape and a compact set of recurrent motif-proximal candidate substitutions to support surveillance and downstream functional validation.
Streptococcus pneumoniae↗
Frequency and clinical significance of bloodstream infections caused by C albicans strains with reduced susceptibility to fluconazole.
Reduced susceptibility to fluconazole (RSF) is relatively common in non-albicans Candida isolates and in Candida albicans recovered from HIV-infected patients with relapsing Candida stomatitis or esophagitis. However, little clinical data on bloodstream infections caused by C. albicans with RSF is available. We analyzed 116 episodes of C. albicans fungemia detected over an 11-year period. Four patients (3.4%) had a blood isolate of C. albicans with RSF. Fluconazole MICs were 16 (3 SDD strains) and 128 microg/ml (1 resistant strain), respectively. Three of the patients were HIV (+) and the fourth was a liver transplant recipient. All of them had been previously treated with an azole compound. The liver recipient had breakthrough fungemia while being treated with 400 mg of preemptive fluconazole despite having an MIC of 16 microg/ml. Fluconazole clinical failure was documented in two of the remaining three cases. Only five other patients with C. albicans fungemia caused by fluconazole-resistant strains (>or=64 microg/ml) are described in the literature. Candida albicans fungemia produced by strains with RSF is still uncommon. It should be suspected in patients previously treated with azole agents or with breakthrough fungemia. In our experience, fluconazole remains a safe option for the treatment of most C. albicans fungemias, although surveillance seems advisable.
Antifungal Agents↗
Mosaic-like structure of penicillin-binding protein 2 Gene (penA) in clinical isolates of Neisseria gonorrhoeae with reduced susceptibility to cefixime.
Neisseria gonorrhoeae strains with reduced susceptibility to cefixime (MICs, 0.25 to 0.5 micro g/ml) were isolated from male urethritis patients in Tokyo, Japan, in 2000 and 2001. The resistance to cephems including cefixime and penicillin was transferred to a susceptible recipient, N. gonorrhoeae ATCC 19424, by transformation of the penicillin-binding protein 2 gene (penA) that had been amplified by PCR from a strain with reduced susceptibility to cefixime (MIC, 0.5 micro g/ml). The sequences of penA in the strains with reduced susceptibilities to cefixime were different from those of other susceptible isolates and did not correspond to the reported N. gonorrhoeae penA gene sequences. Some regions in the transpeptidase-encoding domain in this penA gene were similar to those in the penA genes of Neisseria perflava (N. sicca), Neisseria cinerea, Neisseria flavescens, and Neisseria meningitidis. These results showed that a mosaic-like structure in the penA gene conferred reductions in the levels of susceptibility of N. gonorrhoeae to cephems and penicillin in a manner similar to that found for N. meningitidis and Streptococcus pneumoniae.
Amino Acid Sequence↗
Characterization of Staphylococcus aureus mutants expressing reduced susceptibility to common house-cleaners.
AIMS: To characterize mutants of Staphylococcus aureus expressing reduced susceptibility to house cleaners (HC), assess the impact of the alternative sigma factor SigB on HC susceptibility, and determine the MIC of clinical methicillin-resistant S. aureus (MRSA) to a HC. METHODS AND RESULTS: Susceptibility to HC, HC components, H2O2, vancomycin and oxacillin and physiological parameters were determined for HC-reduced susceptibility (HCRS) mutants, parent strain COL and COLsigB::kan. HCRS mutants selected with three HC expressed reduced susceptibility to multiple HC, HC components, H2O2 and vancomycin. Two unique HCRS mutants also lost the methicillin resistance determinant. In addition, all HCRS mutants exhibited better growth at two temperatures, and one HCRS mutant expressed reduced carotenoid production. COLsigB::kan demonstrated increased susceptibility to all HC and many HC components. sigB operon mutations were not detected in one HCRS mutant background. Of 76 clinical MRSA, 20 exhibited reduced susceptibility to a HC. CONCLUSIONS: HCRS mutants demonstrate altered susceptibility to multiple antimicrobials. While sigB is required for full HC resistance, one HCRS mechanism does not involve sigB operon mutations. Clinical MRSA expressing reduced susceptibility to a common HC were detected. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that HCRS mutants are not protected against, nor selected by, practical HC concentrations.
Disinfectants↗
Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates.
An association between reduced susceptibility to echinocandins and changes in the 1,3-beta-d-glucan synthase (GS) subunit Fks1p was investigated. Specific mutations in fks1 genes from Saccharomyces cerevisiae and Candida albicans mutants are described that are necessary and sufficient for reduced susceptibility to the echinocandin drug caspofungin. One group of amino acid changes in ScFks1p, ScFks2p, and CaFks1p defines a conserved region (Phe 641 to Asp 648 of CaFks1p) in the Fks1 family of proteins. The relationship between several of these fks1 mutations and the phenotype of reduced caspofungin susceptibility was confirmed using site-directed mutagenesis or integrative transformation. Glucan synthase activity from these mutants was less susceptible to caspofungin inhibition, and heterozygous and homozygous Cafks1 C. albicans mutants could be distinguished based on the shape of inhibition curves. The C. albicans mutants were less susceptible to caspofungin than wild-type strains in a murine model of disseminated candidiasis. Five Candida isolates with reduced susceptibility to caspofungin were recovered from three patients enrolled in a clinical trial. Four C. albicans strains showed amino acid changes at Ser 645 of CaFks1p, while a single Candida krusei isolate had a deduced R1361G substitution. The clinical C. albicans mutants were less susceptible to caspofungin in the disseminated candidiasis model, and GS inhibition profiles and DNA sequence analyses were consistent with a homozygous fks1 mutation. Our results indicate that substitutions in the Fks1p subunit of GS are sufficient to confer reduced susceptibility to echinocandins in S. cerevisiae and the pathogens C. albicans and C. krusei.
Amino Acid Substitution↗
Real-time PCR detection and frequency of 16S rDNA mutations associated with resistance and reduced susceptibility to tetracycline in Helicobacter pylori from England and Wales.
OBJECTIVES: To investigate the occurrence of 16S rDNA mutations associated with resistance or reduced susceptibility to tetracycline in Helicobacter pylori isolated in England and Wales, and to develop a real-time PCR assay to detect these DNA polymorphisms from culture and gastric biopsies. METHODS: Tetracycline susceptibility was determined by disc diffusion. The MIC of isolates with reduced susceptibility was determined by Etest and agar dilution methods. The 16S rDNA of these isolates was sequenced and resistance-associated mutations identified. A LightCycler assay developed to detect these mutations was applied to DNA extracted from culture and gastric biopsies. RESULTS: From 1006 isolates of H. pylori examined, 18 showed reduced susceptibility to tetracycline. Of these, three were resistant (>or=4 mg/L). Mutations in 16S rDNA were detected in 10 of the reduced susceptibility isolates: one double base mutation of A926T/A928C, one A926C, one A928C; and seven A926G. The first two polymorphisms were novel and had not been reported from clinical isolates previously. The LightCycler assay identified each of the 10 isolates with 16S rDNA mutations, but did not detect polymorphisms in 100 tetracycline-susceptible H. pylori isolates. The assay correctly determined the tetracycline susceptibility of H. pylori in 20 gastric biopsy samples. CONCLUSIONS: Mutations in 16S rDNA were detected in H. pylori isolated in England and Wales with reduced susceptibility to tetracycline, but resistance to this antibiotic was uncommon. We show molecular-based susceptibility testing for tetracycline is possible direct from biopsy material.
DNA, Ribosomal↗
Citywide emergence of Pseudomonas aeruginosa strains with reduced susceptibility to polymyxin B.
OBJECTIVES: To determine the prevalence of Pseudomonas aeruginosa isolates with reduced susceptibility to polymyxin B, and to assess the in vitro activity of antibiotic combinations. METHODS: All unique patient isolates of P. aeruginosa were collected from 11 Brooklyn, NY hospitals during a three month period in 2003. Isolates with reduced susceptibility to polymyxin B (MIC > 2 mg/L) underwent ribotyping. The activity of polymyxin B combined with rifampicin, azithromycin and/or imipenem was tested by the chequerboard and time-kill methods against a subset of isolates. RESULTS: Of 527 isolates, only 61% were susceptible to imipenem. Twenty-five isolates (5%), from 8/11 hospitals, had reduced susceptibility to polymyxin B (MICs 4-8 mg/L), compared with 0/691 isolates collected in 2001. Ten of 25 were resistant to multiple other antibiotic classes. Ribotyping of the isolates revealed 19 unique types. Chequerboard testing of the 10 multiresistant isolates demonstrated synergy for the combinations of polymyxin B with azithromycin, imipenem and rifampicin in 6, 2, and 1 isolates, respectively. Time-kill studies revealed bactericidal activity for the following antibiotics when combined with polymyxin B: imipenem plus rifampicin against all 10 isolates, rifampicin in 9/10 isolates, imipenem in 8/10 isolates and azithromycin in 4/10 isolates. MICs of bacteria surviving incubation in polymyxin B alone rose for 4/9 isolates (MIC range 12-48 mg/L). CONCLUSIONS: P. aeruginosa with reduced susceptibility to polymyxin B have emerged in multiple strains in Brooklyn, NY. Combinations of polymyxin B with rifampicin and/or imipenem are bactericidal. The clinical utility of these combinations remains to be determined.
Anti-Bacterial Agents↗
Amino acid substitutions in mosaic penicillin-binding protein 2 associated with reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae.
The molecular mechanisms of reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae, particularly amino acid substitutions in mosaic penicillin-binding protein 2 (PBP2), were examined. The complete sequence of ponA, penA, and por genes, encoding, respectively, PBP1, PBP2, and porin, were determined for 58 strains isolated in 2002 from Japan. Replacement of leucine 421 by proline in PBP1 and the mosaic-like structure of PBP2 were detected in 48 strains (82.8%) and 28 strains (48.3%), respectively. The presence of mosaic PBP2 was the main cause of the elevated cefixime MIC (4- to 64-fold). In order to identify the mutations responsible for the reduced susceptibility to cefixime in isolates with mosaic PBP2, penA genes with various mutations were transferred to a susceptible strain by genetic transformation. The susceptibility of partial recombinants and site-directed mutants revealed that the replacement of glycine 545 by serine (G545S) was the primary mutation, which led to a two- to fourfold increase in resistance to cephems. Replacement of isoleucine 312 by methionine (I312M) and valine 316 by threonine (V316T), in the presence of the G545S mutation, reduced susceptibility to cefixime, ceftibuten, and cefpodoxime by an additional fourfold. Therefore, three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.
Amino Acid Sequence↗
Emergence of reduced susceptibility and resistance to fluoroquinolones in Escherichia coli in Taiwan and contributions of distinct selective pressures.
A survey of 1,203 Escherichia coli isolates from 44 hospitals in Taiwan revealed that 136 (11.3%) isolates were resistant to fluoroquinolones and that another 261 (21.7%) isolates had reduced susceptibility. Resistance was more common in isolates responsible for hospital-acquired (mostly in intensive care units) infections (17.5%) than in other adult inpatient (11.4%; P = 0.08) and outpatient isolates (11.9%; P > 0.1). Similarly, reduced susceptibility was more common in isolates responsible for hospital-acquired infections (30.9%) than in other adult inpatient (21.0%; P = 0.04) and outpatient (21.4%; P = 0.06) isolates. Isolates from pediatric patients were less likely to be resistant (1.3 versus 12.0%; P < 0.01) but were nearly as likely to have reduced susceptibility (17.7 versus 21.9%; P > 0.1) as nonpediatric isolates. There was an inverse relationship in the proportion of isolates that were resistant versus the proportion that had reduced susceptibility among isolates from individual hospitals (R = 0.031; P < 0.05). In an analysis of isolates from two hospitals, all 9 resistant strains possessed double point mutations in gyrA and all 19 strains with reduced susceptibility strains had single point mutations; no mutations were found among fully susceptible strains. Risk factors for resistance included underlying cancer (odds ratio [OR], 83; 95% confidence interval [CI(95)], 7.3 to 2,241; P < 0.001), exposure to a quinolone (OR, undefined; P = 0.02), and exposure to a nonquinolone antibiotic (OR, 20; CI(95), 2.2 to 482; P < 0.001); underlying cancer was the only independent risk factor (OR, 83; CI(95), 8.6 to 807; P < 0.001). There were no significant associations between any of these factors and reduced susceptibility. Whereas acute and chronic quinolone use in cancer patients is a major selective pressure for resistance, other undetermined but distinct selective pressures appear to be more responsible for reduced susceptibility to fluoroquinolones in E. coli.
Adolescent↗
Borderline methicillin-susceptible Staphylococcus aureus strains have more in common than reduced susceptibility to penicillinase-resistant penicillins.
Ten epidemiologically unrelated Staphylococcus aureus isolates with borderline levels of susceptibility to antistaphylococcal penicillinase-resistant penicillins (PRPs) were investigated together with appropriate S. aureus control strains. By a nitrocefin microplate assay, all borderline PRP-susceptible test strains were found to produce comparable amounts of beta-lactamase. Hydrolytic activity against another chromogenic substrate (PADAC) and against the PRPs was also demonstrated in membrane preparations from induced cells of 9 of the 10 borderline test strains. When bacterial membranes were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, two methicillin-inducible bands of about 32 and 31 kDa were detected, after Coomassie blue staining, in the membrane protein patterns of the same nine borderline test strains. By gel renaturation and zymographic detection of beta-lactamase activity, both methicillin-inducible membrane proteins were detected with nitrocefin as a substrate, whereas only one band (presumably the smaller protein) was detected with PADAC. With the remaining borderline test strain (a40), only the larger band was detected in the renatured gels with nitrocefin as a substrate. Plasmid DNA analysis revealed that the borderline susceptible test strains, again with the exception of a40, shared a 17.2-kb plasmid yielding four HindIII fragments of 7.0, 5.3, 3.5, and 1.4 kb. In Western blot (immunoblot) experiments using rabbit antiserum to penicillin-binding protein (PBP) 2a, test strain a40, which did not share a number of features characteristically associated with the other borderline test strains, was eventually shown to produce PBP 2a. Five other S. aureus strains, belonging to phage group 94/96, were found to display the borderline phenotype, including such distinguishing features as the membrane-associated PRP- and PADAC-hydrolyzing activity, the two methicillin-inducible membrane proteins, and the 17.2-kb plasmid. These results suggest that borderline susceptible S. aureus strains share more common features than reduced susceptibility to PRPs.
Bacterial Proteins↗
Efficacy of telithromycin in community-acquired pneumonia caused by pneumococci with reduced susceptibility to penicillin and/or erythromycin.
BACKGROUND: The efficacy of oral telithromycin was assessed in patients with community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae with reduced susceptibility to penicillin and/or erythromycin. METHODS: Patients with CAP who had received telithromycin 800 mg once daily for 5 or 7-10 days (n = 2,289) in eight phase III clinical trials, or telithromycin 800 mg once daily for 7 days (n = 50) in a phase II study were included in this pooled analysis. Patients with S. pneumoniae as the cause of infection were identified, with particular focus on those infected with strains with reduced susceptibility to penicillin (intermediate, minimal inhibitory concentration (MIC) 0.12-1.0 mg/l; resistant, MIC >or=2.0 mg/l) and/or resistance to erythromycin (MIC >or=1.0 mg/l). Per-protocol clinical and bacteriological outcomes were assessed 7-14 days post-therapy in the phase III studies, and at 7-21 days post-therapy or at the end of therapy in the phase II study. RESULTS: Of the 327 telithromycin-treated patients with S. pneumoniae infection, 61 (19%) were infected with strains with reduced susceptibility to penicillin and/or erythromycin. Clinical cure and bacterial eradication rates in these patients were 91.8% (56/61) and 93.4% (57/61), respectively. Corresponding clinical cure and bacterial eradication rates overall for all isolates of pneumococci were 94.5% (309/327) and 96.0% (314/327), respectively. All isolates with reduced susceptibility to penicillin and/or erythromycin were susceptible to telithromycin (MIC <or=1.0 mg/l). CONCLUSION: These results indicate that telithromycin is an effective oral antibacterial for the treatment of CAP caused by pneumococci with reduced susceptibility to penicillin and/or erythromycin.
Administration, Oral↗
Beta-lactam susceptibility of Haemophilus influenzae strains showing reduced susceptibility to cefuroxime.
Minimum inhibitory concentrations of 13 beta-lactam antibiotics (ampicillin, amoxycillin, amoxycillin/clavulanate, imipenem, cefazolin, cefadroxil, cefaclor, cefuroxime, cefotaxime, cefepime, cefpirome, cefpodoxime and cefixime), were determined for 76 strains of beta-lactamase negative Haemophilus influenzae, isolated over a five year period (1985-1990) that gave reduced zones to cefuroxime on disc testing when compared to the control strain H. influenzae NCTC 11931. MIC90 values for all antibiotics (except imipenem) were approximately ten times higher than the MIC90 values for a susceptible control group. Increased resistance was not associated with any particular biotype, although three biotype III strains were highly resistant to imipenem. More than 50% of strains with reduced susceptibility to beta-lactam antibiotics were isolated from patients with chronic respiratory disease. Published data on the sputum concentration of each antibiotic were compared to the MIC90 values obtained for the susceptible and resistant strains.
Anti-Bacterial Agents↗
Survey of plasmid-associated genetic markers in enterobacteriaceae with reduced susceptibilities to cephalosporins.
Clinical isolates of Enterobacteriaceae with reduced susceptibilities to cephalosporins were collected from 1993 to 2000. The organisms were screened for the extended-spectrum beta-lactamase (ESBL) phenotype, and plasmid extracts were screened for genetic markers by hybridization. A bla(TEM) probe was derived from pUC19; other probes were derived from pACM1, the plasmid responsible for the first known appearance of an ESBL in our institution. These probes included bla(SHV), int, aac(3)-Ia, dfrA1, IS6100, tetA, IncM markers, and Anon 13, a marker for the Klebsiella pneumoniae chromosomal sequences that flank bla(SHV-5). There were 42 hybridization patterns among 237 isolates. Patterns designated pACM1-like occurred in 44% of the isolates (eight species) and were always associated with the clavulanic acid (CA)-susceptible ESBL phenotype. The TEM marker was not predictive of the ESBL phenotype. Mapping indicated the presence of an SHV marker and up to 7.5 kb of its flanking chromosomal sequences in three non-IncM plasmids obtained in transformation experiments. We theorize that this DNA segment spread to other plasmids from pACM1-like sources. CA insensitivity became more frequent with time and was usually associated with either the TEM marker or the absence of both bla markers. One plasmid-encoded enzyme with characteristics of an AmpC beta-lactamase was observed in a transformant lacking both TEM and SHV markers. Although SHV type ESBLs were a continuing source of reduced susceptibility to cephalosporins in our institution, organisms with different resistance mechanisms were added to the hospital microflora in later years. These changes might be related, in part, to ESBL control strategies implemented in 1995.
Adult↗
Reduced susceptibility to azithromycin and high percentages of penicillin and tetracycline resistance in Neisseria gonorrhoeae isolates from Manaus, Brazil, 1998.
BACKGROUND: The identification of Neisseria gonorrhoeae isolates resistant to antimicrobial agents currently recommended for the treatment of gonococcal infections continues to escalate globally. Thus, in some areas, resistance to fluoroquinolone drugs is commonplace; several reports document resistance to third-generation cephalosporins, and the sporadic isolation of spectinomycin-resistant isolates continues unabated. Gonococcal resistance to azithromycin, an antibiotic used for the primary treatment of gonococcal infections in some Latin American countries, also has been described. Because the prevalence of resistant isolates is insufficiently documented in many areas of Latin America, the efficacy of locally recommended therapies for gonococcal infections is often unknown. GOAL: To determine the antimicrobial susceptibility and strain types of N gonorrhoeae isolates collected in Manaus, Brazil. These data will establish antimicrobial susceptibility baseline data for the region as a reference point for future surveillance. STUDY DESIGN: Consecutive N gonorrhoeae isolates from urethral and endocervical specimens were collected and examined for identity, antimicrobial susceptibility, and strain type (plasmid content, tetM type, auxotype, and serovar). RESULTS: Most of the isolates (65/81; 85.2%) were resistant to tetracycline, penicillin, or both, with the majority (n = 62) carrying plasmid-mediated resistance to tetracycline (tetracycline-resistant N gonorrhoeae [TRNG]). All of the TRNG contained the Dutch-type tetM plasmid, and 18 were A/S class NR/IA-02. Penicillinase-producing N gonorrhoeae comprised 8.2% (7/81) of the isolates. Of these seven isolates, four also were TRNG, and two carried chromosomal resistance to tetracycline. The isolates were susceptible to ciprofloxacin, spectinomycin, and ceftriaxone. However, 23 isolates were characterized by reduced susceptibility to azithromycin (MIC, 0.25-0.5 microg/ml), and one isolate had reduced susceptibility to ciprofloxacin (MIC, 0.25 microg/ml). CONCLUSIONS: This study supports the continued use of third-generation cephalosporins, spectinomycin, and fluoroquinolone drugs for the primary treatment of gonococcal infections in Manaus. The occurrence of isolates with reduced susceptibility to azithromycin and ciprofloxacin underscores the importance of ongoing antimicrobial susceptibility monitoring to support decisions regarding appropriate drugs for the treatment of gonococcal infections.
Anti-Bacterial Agents↗
Multilocus sequence typing (MLST) shows that the 'Iberian' clone of methicillin-resistant Staphylococcus aureus has spread to France and acquired reduced susceptibility to teicoplanin.
Infection by methicillin-resistant Staphylococcus aureus (MRSA) presents a serious problem, as these organisms are resistant to a wide range of antibiotics. Moreover, MRSA with reduced susceptibility to glycopeptides (GISA) have emerged in recent years. In our hospital we were faced with an outbreak of GISA between January and March 2000, involving six patients who were free of MRSA when the GISA isolate emerged, and five of whom had not been given glycopeptides. The initial GISA isolate from the six patients was compared with six 'historical' multiple-resistant MRSA isolates (1996-1999), which had not been found to be GISA by the routinely used method. Antibiotic susceptibility was studied through the disc diffusion method, and MICs of glycopeptides were determined by Etest, agar and broth dilution techniques. Molecular strain typing was done by PFGE and multilocus sequence typing (MLST). All 12 isolates that belonged to the gentamicin-resistant group of MRSA were susceptible to vancomycin, but showed reduced susceptibility to teicoplanin through at least one MIC method. PFGE typing yielded five different but closely related profiles, and eight of the 12 clinical isolates were classified into a single PFGE type. MLST yielded an identical allelic profile for all 12 isolates, corresponding to the profile (3-3-1-12-4-4-16) of the 'Iberian' clone HPV107 of MRSA. MLST allowed us to confirm the presence of the 'Iberian' MRSA clone HPV107 with the same allelic profile in our hospital for several years. We can now note that strains of this clone have acquired reduced susceptibility to teicoplanin.
Anti-Bacterial Agents↗
Reduced susceptibility of Staphylococcus aureus to vancomycin--a review of current knowledge.
Antibiotic options for patients with methicillin resistant Staphylococcus aureus infections are severely limited. Unfortunately, infections with S. aureus with reduced susceptibility to vancomycin and teicoplanin have been recently reported for the first time. Commonly used laboratory methods for determining antibiotic susceptibility may be inadequate for detecting reduced susceptibility to vancomycin. Even though no confirmed cases have yet been detected in Australia, a high index of suspicion must be maintained for the occurrence of such organisms. Strategies for prevention of the spread of S. aureus with reduced susceptibility to vancomycin should be prepared by Australian hospitals prior to their first cases being identified. This article outlines the background to this developing issue and discusses laboratory methods and findings, with some current recommendations for diagnostic laboratories.
Australia↗