Extended-spectrum beta-lactamases in Ireland,including a novel enzyme,TEM-102

Organisms producing extended-spectrum beta-lactamases (ESBLs) have been reported in many countries, but there is no information on the prevalence of ESBL-producing members of the family Enterobacteriaceae in Ireland. A total of 925 isolates of ampicillin-resistant members of the Enterobacteriaceae were received from six hospitals in Ireland over a 3-year period from September 1996 to September 1999. Isolates were screened for ESBL production by the double-disk diffusion (DDD) method. DDD-positive isolates that were (i) confirmed as ESBL producers by National Committee for Clinical Laboratory Standards (NCCLS) confirmatory testing and (ii) susceptible to cefoxitin by disk diffusion were considered ESBL producers. By these criteria, 27 (3%) of the ampicillin-resistant members of the Enterobacteriaceae studied were categorized as ESBL producers. Molecular typing suggested that some intra- and interhospital spread of ESBL-producing isolates had occurred. DNA sequencing of amplified bla(TEM) and bla(SHV) genes resulted in the detection of a novel bla(TEM) ESBL gene, bla(TEM-102) in two isolates (Klebsiella pneumoniae and Enterobacter cloacae) received from the same hospital but isolated from different patients. The study suggests dissemination of ESBL-producing bacteria within the health care system in Ireland and emphasizes the need for measures to control such spread.     

Clinical significance of extended-spectrum beta-lactamases

The spread of extended-spectrum beta-lactamases (ESBLs) in nosocomial and community-acquired enterobacteria is an important challenge for clinicians as the therapeutic options for these organisms are limited. The emergence of ESBL-producing Escherichia coli in the community, associated with the spread of CTX-M ESBL, is one of the most significant epidemiologic changes in infectious diseases during recent years. The epidemiology of these infections is complex and combines the expansion of mobile genetic elements with clonal spread. Infections caused by ESBL producers are associated with increased mortality, length of stay and increased cost. An inadequate empirical therapy for serious infections caused by these organisms is independently associated with increased mortality. Carbapenems are the drugs of choice for serious infections caused by ESBL-producing organisms but their overuse is a cause of concern.     

Clinical significance of extended-spectrum β-lactamases

The spread of extended-spectrum β-lactamases (ESBLs) in nosocomial and community-acquired enterobacteria is an important challenge for clinicians as the therapeutic options for these organisms are limited. The emergence of ESBL-producing Escherichia coli in the community, associated with the spread of CTX-M ESBL, is one of the most significant epidemiologic changes in infectious diseases during recent years. The epidemiology of these infections is complex and combines the expansion of mobile genetic elements with clonal spread. Infections caused by ESBL producers are associated with increased mortality, length of stay and increased cost. An inadequate empirical therapy for serious infections caused by these organisms is independently associated with increased mortality. Carbapenems are the drugs of choice for serious infections caused by ESBL-producing organisms but their overuse is a cause of concern.     

Prevalence of AmpC and other beta-lactamases in enterobacteria at a large urban university hospital in Brazil

Production of extended-spectrum beta-lactamases (ESBLs) has been reported in virtually all species of Enterobacteriaceae, which greatly complicates the therapy for infections caused by these organisms. However, the frequency of isolates producing AmpC beta-lactamases, especially plasmid-mediated AmpC (pAmpC), is largely unknown. These beta-lactamases confer resistance to extended-spectrum cephalosporins and aztreonam, a multidrug-resistant (MDR) profile. The aim of the present study was to determine the occurrence of ESBL and pAmpC beta-lactamases in a hospital where MDR enterobacterial isolates recently emerged. A total of 123 consecutive enterobacterial isolates obtained from 112 patients at a university hospital in Rio de Janeiro, Brazil, during March to June 2001 were included in the study. ESBL was detected by the addition of clavulanate to cephalosporin containing disks and by double diffusion. AmpC production was evaluated by a modified tridimensional test and a modified Hodge test. The presence of plasmid-mediated ampC beta-lactamase genes was evaluated by multiplex polymerase chain reaction. Sixty-five (53%) of 123 enterobacterial isolates were MDR obtained from 56 patients. ESBL production was detected in 35 isolates; 5 clonal Escherichia coli isolates exhibited high levels of chromosomal AmpC and ESBL production. However, no isolates contained pAmpC genes. Infection or colonization by MDR enterobacteria was not associated with any predominant resistant clones. A large proportion of hospital infections caused by ESBL-producing enterobacteria identified during the study period were due to sporadic infections rather than undetected outbreaks. This observation emphasizes the need to improve our detection methods for ESBL- and AmpC-producing organisms in hospitals where extended-spectrum cephalosporins are in wide use.     

In vitro susceptibility of recent antibiotic-resistant urinary pathogens to ertapenem and 12 other antibiotics

Background: The treatment of complicated urinary tract infections may require the use of a parenteral antibiotic with potent activity against the most common urinary pathogens. Ertapenem is a broad-spectrum 1beta-methyl carbapenem with a long plasma half-life that allows administration of a single daily dose. METHODS: The purpose of this work was to test the in vitro susceptibility to ertapenem, ampicillin, cefazolin, cefuroxime, cefotaxime, co-amoxiclav, piperacillin/tazobactam, imipenem, gentamicin, amikacin, fosfomycin, ciprofloxacin and co-trimoxazole of 482 strains of urinary pathogens of the family Enterobacteriaceae isolated from patients in the community of Madrid (40% from males). The distribution was as follows: Escherichia coli (n = 315), Proteus mirabilis (n = 42), Klebsiella spp. (n = 14) and AmpC-producing Enterobacteriaceae (n = 111). The strains studied were selected based on their resistance to quinolones and aminoglycosides, and their production of extended-spectrum beta-lactamases (ESBLs) or AmpC-type beta-lactamases. RESULTS: All the strains were susceptible to ertapenem, imipenem and amikacin. The MIC(90) of ertapenem ranged from a minimum of 0.03 mg/L for Proteus vulgaris and a maximum of 1 mg/L for Enterobacter spp. Ertapenem was the most active of all drugs tested in all cases. On comparing antibiotic resistance among ESBL-producing strains of E. coli (n = 35) and E. coli strains not producing ESBLs (n = 280), statistically significant differences were obtained for ciprofloxacin (P = 0.002) and gentamicin (P = 0.011). Regarding ertapenem, only a slight increase in MIC(50) was seen, the value being 0.015 mg/L for strains not producing ESBLs versus 0.03 mg/L for ESBL-producing strains. CONCLUSIONS: In view of its significant antibiotic potency against antibiotic-resistant Enterobacteriaceae, ertapenem may constitute a good therapeutic alternative in urinary infections caused by these pathogens.     

Surveillance of extended-spectrum beta-lactamases from clinical samples and faecal carriers in Barcelona, Spain

OBJECTIVES: The aim of the present study was to characterize and compare the extended-spectrum beta-lactamase (ESBL)-producing organisms isolated from clinical samples and faecal carriers in 2001 and 2002. METHODS: A total of 5251 Enterobacteriaceae isolated from clinical samples and 1321 stool samples were evaluated for the presence of ESBLs. The stool samples were spread onto plates of MacConkey agar containing 2 mg/L cefotaxime for selection of ESBL-producing strains. These strains were defined as those showing synergism between amoxicillin/clavulanic acid and third-generation cephalosporins. The beta-lactamases involved were characterized by isoelectric focusing, PCR assays and DNA sequencing. RESULTS: The prevalence of ESBL-producing strains among clinical Enterobacteriaceae was 1.7%. Of these, 87.6% produced CTX-M, 25.8% produced SHV and 2.2% were TEM-type-producing strains. All clinical ESBL-producing strains were Escherichia coli, with the exception of four Klebsiella pneumoniae and one Citrobacter freundii. The prevalence of faecal carriage of ESBL-producing organisms was 3.3%. Of these, 75% produced CTX-M-type enzymes followed by 22.7% SHV-producing strains. All faecal ESBL-producing strains were E. coli except for one Enterobacter cloacae and one Proteus mirabilis. This latter strain produced the PER-1 enzyme reported for the first time in Spain. CONCLUSIONS: The prevalence of ESBL-producing strains in stool samples was higher than that observed in clinical samples from the same period. The different types of ESBLs found were similar in both contexts. The most prevalent ESBLs were the CTX-M-related enzymes, with nine different types, followed by SHV-12.     

Investigation of extended-spectrum beta-lactamase in Klebsiellae pneumoniae and Escherichia coli from China

Extended-spectrum beta-lactamases (ESBLs) are an increasing cause of resistance to third-generation cephalosporins in Enterobacteriaceae. However, they have not been well studied in China. We investigated the prevalence, resistance, and probable gene type of ESBLs using MICs testing and polymerase chain reaction in 559 Klebsiellae pneumoniae and 427 Escherichia coli isolates collected from patients in Huashan Hospital from 1 January to 31 December 1999. The incidence of ESBL-producing strains was 51% among Klebsiellae pneumoniae (285/559) and 23.6% among Escherichia coli (101/427), most of which were collected from patients in intensive care unit and neurosurgical ward. PFGE showed that some epidemic ESBL-producing strains were present in the ICU, especially among ESBL-producing Klebsiellae pneumoniae. The major source of ESBL-producing Klebsiellae pneumoniae and Escherichia coli was sputum specimen (63.5%) and urine (64.3%), respectively. These strains were resistant to most beta-lactams (including the third-generation cephalosporins and monobactams) and non-beta-lactams (such as fluoroquinolones, aminoglycosides, tetracycline, and chloramphenicol), all or most ESBL producers were susceptible to imipenem, cefmetazole and beta-lactam/clavulanic acid. TEM was the main type of beta-lactamases and the CTX-M type of ESBLs was common in these isolates. Some ESBL-producing Escherichia coli and most ESBL-producing Klebsiellae pneumoniae produced more than one type of beta-lactamase. These data confirm that ESBL producers are common among hospital strains of Escherichia coli and Klebsiellae pneumoniae in China. It is important to monitor such strains closely and prevent their spread.     

Prevalence and Molecular Characterization of Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in a Pediatric Patient Population

Very little is known about the prevalence and composition of various types of extended-spectrum β-lactamases (ESBL) in pediatric patients. The aims of this study were the following: (i) to determine the prevalence of ESBLs among Enterobacteriaceae in a tertiary-care pediatric population; (ii) to characterize the genetic composition of the identified ESBL enzymes; and (iii) to determine the relative prevalence of CTX-M enzymes and Escherichia coli ST131 strains among ESBL-producing isolates in the same pediatric patient population. Among the 1,430 Enterobacteriaceae isolates screened for elevated MICs to cefotaxime and/or ceftazidime from pediatric patients during a 1-year period, 94 isolates possessed at least one ESBL gene. CTX-M was the most commonly isolated ESBL type, consisting of 74% of all ESBLs versus 27% TEM and 24% SHV enzymes. Sequence analysis and probe-specific real-time PCR revealed that the majority (80%) of the CTX-M-type ESBLs were CTX-M-15 enzymes, followed by CTX-M-14 (17%) and CTX-M-27(2.8%). Multilocus sequence typing (MLST) and repetitive PCR analyses revealed that the relative prevalence of ST131 among ESBL-producing E. coli isolates is 10.2%. This study highlights the growing problem of ESBL resistance in pediatric Enterobacteriaceae isolates and demonstrates a transition toward the predominance of CTX-M-type enzymes among ESBL-producing Enterobacteriaceae organisms causing pediatric infections.     

Antimicrobial resistance in Enterobacteriaceae in Brooklyn, NY: epidemiology and relation to antibiotic usage patterns

In November 1997, all Enterobacteriaceae isolated at 15 hospitals in Brooklyn were collected. Extended-spectrum beta-lactamases (ESBLs) were present in 44% of 409 Klebsiella pneumoniae isolates. Six isolates had reduced susceptibility to carbapenems, including two that were not susceptible to any of the antibiotics tested. Pulsed field gel electrophoresis revealed a commonality of resistant isolates within and between hospitals. The occurrence of ESBLcontaining isolates was associated with cephalosporin usage (P = 0.055). ESBLs were present in 4.7% of Escherichia coli and 9.5% of Proteus mirabilis isolates. It is concluded that ESBL-producing Enterobacteriaceae are endemic in Brooklyn, are spread between hospitals, and may be associated with cephalosporin usage.     

Prevalence and mechanisms of cephalosporin resistance in Enterobacteriaceae in London and South-East England

OBJECTIVES: To investigate the molecular epidemiology of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in London and South-East England. METHODS: A prospective study involving 16 hospital microbiology laboratories in London and South-East England was undertaken over a 12 week period. Each laboratory submitted up to 100 consecutive cephalosporin-resistant Enterobacteriaceae isolates judged clinically significant by microbiology staff. Centralized testing was undertaken to confirm organism identification and cephalosporin resistance and to analyse resistance mechanisms. RESULTS: The predominant mechanism of cephalosporin resistance in isolates from both hospital and community settings was the production of CTX-M-type ESBLs, with CTX-M-producing Escherichia coli as the most numerous resistant organism overall. Other major mechanisms of cephalosporin resistance included production of non-CTX-M ESBLs and AmpC beta-lactamases. Most ESBL (both CTX-M and non-CTX-M) producers were multiply resistant to non-beta-lactam antibiotics, including trimethoprim, ciprofloxacin and gentamicin. CONCLUSIONS: CTX-M enzymes, which were unrecorded in the UK prior to 2000, have become the major mechanism of cephalosporin resistance in Enterobacteriaceae in South-East England. E. coli has overtaken Klebsiella and Enterobacter spp. to become the major host for ESBLs. Due to the multiple antibiotic resistance exhibited by many ESBL-producers, these changes have major implications for antimicrobial therapy.     

Performance in detection and reporting beta-lactam resistance phenotypes in Enterobacteriaceae: a nationwide proficiency study in Italian laboratories

We evaluated the ability of 60 Italian clinical microbiology laboratories in detecting and reporting beta-lactam resistance phenotypes in Enterobacteriaceae. Laboratories received 5 well-characterized isolates producing extended-spectrum beta-lactamases (ESBLs), 2 hyperproducers of chromosomal enzymes, and 3 quality control strains. The performances in antimicrobial susceptibility testing (AST) were different depending on the species and type of ESBL produced. High rates of very major errors (up to 56%) were observed for ESBL producers when testing cephalosporins and aztreonam, especially in the case of CTX-M-1-producing Escherichia coli and TEM-52-producing Proteus mirabilis. Isolates hyperproducing chromosomal enzymes were erroneously reported as ESBL producers in approximately 20% of cases. Detection of ESBLs is still a problem for clinical microbiology laboratories. Overall, performances in AST appear to be better with Klebsiella spp. producing well-known enzymes (e.g., SHV type) than with strains producing emerging enzymes (e.g., CTX-M type) or organisms not well recognized as ESBL producers (e.g., P. mirabilis).     

Risk factors for community-onset urinary tract infections due to Escherichia coli harbouring extended-spectrum beta-lactamases

OBJECTIVES: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have been increasingly recognized in the community. The aim of this study was to determine the prevalence, types of ESBLs and risk factors for community-onset ESBL-producing E. coli in urinary tract infections (UTIs). METHODS: Adults with community-onset UTIs due to ESBL-producing E. coli (cases) and non-ESBL-producing E. coli (controls) were identified through records of the clinical microbiology laboratory of the hospital. Two different periods were studied: from January 2000 to January 2001 and from October to December 2003. Controls were matched in a 3:1 ratio to case patients according to age, sex, date of isolation and residence in a long-term care facility. Potential risk factors were recorded. Isoelectric focusing as well as PCR and DNA sequencing were used to characterize the bla(TEM), bla(SHV) and bla(CTX-M) genes. A possible clonal relationship among the strains was determined by repetitive extragenic palindromic sequence PCR. RESULTS: The prevalence of infection due to ESBL-producing E. coli increased from 0.47% in 2000 to 1.7% in 2003 (P < 0.001). Community-onset ESBL-producing E. coli infection shifted from 50% in the first period to 79.5% in 2003 (P < 0.001). Nineteen cases and 55 matched controls of community-onset ESBL-producing E. coli UTI were included. ESBL-producing E. coli strains were clonally unrelated. On univariate analysis, genitourinary pathology (P < 0.03), previous bacterial infection (P = 0.01), intravenous antibiotic treatment (P = 0.01), hospitalization in the previous 12 months (P = 0.04) and previous exposure to oral second-generation cephalosporins (P < 0.05) were associated with community-onset infection due to ESBL-producing E. coli. In our regression model, only previous exposure to second-generation cephalosporins was strongly associated with E. coli harbouring ESBLs (OR, 21.42; CI 95%, 5.38-85.22; P < 0.05). In the first period, only TEM- and SHV-derived ESBLs were identified. The enzymes were characterized as members of the TEM group (60%), SHV group (16%) and CTX-M group (24%). CONCLUSIONS: We detected a marked increase in infections due to ESBL-producing E. coli, especially in the community, in the periods studied. Only previous exposure to the oxyimino cephalosporin cefuroxime, and not to ciprofloxacin, aminoglycosides or third-generation cephalosporins, was predictive of an ESBL-producing E. coli community-onset infection in our area. The emergence of the CTX-M type of beta-lactamase in E. coli follows closely the spread of ESBLs in community isolates.     

Antibiotic susceptibility of bacterial strains isolated from urinary tract infections in Poland

Worldwide data show that there is increasing resistance among urinary tract pathogens to conventional drugs. The aim of this study was to obtain data on susceptibility patterns of pathogens responsible for urinary tract infections (UTIs) in Poland to currently used antimicrobial agents. A multicentre study of 141 pathogens from hospital-acquired infections and 460 pathogens from community-acquired infections was carried out between July 1998 and May 1999. The most prevalent aetiological agent was Escherichia coli (73.0%), followed by Proteus spp. (8.9%) and other species of Enterobacteriaceae (9.6%). Few community infections were caused by Gram-positive bacteria (2.2%). Gram-positive cocci were isolated more frequently from a hospital setting (14.1%) and the most common were Enterococcus spp. (8.5%). Pseudomonas aeruginosa was found only among hospital isolates and was responsible for 10.7% of infections. E. coli isolates from both community and hospital infections were highly susceptible to many antimicrobial agents with the exception of those isolates producing extended-spectrum beta-lactamases (ESBLs). Of all Enterobacteriaceae tested, 38 strains (6.9%) were capable of producing ESBLs.     

The problem of complicated skin and skin structure infections: the need for new agents

Complicated skin and skin structure infections (cSSSIs) continue to pose a significant clinical challenge. The most frequent cause of these infections is Staphylococcus aureus, although other organisms, including Streptococcus pyogenes and, in certain circumstances, Enterobacteriaceae, are also involved. The relentless increase in methicillin resistance among S. aureus isolated in hospitals throughout the world has made it important to provide coverage for these organisms when treating cSSSIs in hospitals. More recently, however, there has been a striking increase in methicillin resistance among staphylococci isolated from infections acquired in the community, particularly in the USA. As a result, previous recommendations for empirical therapy of these important infections are now outdated. The papers in this Supplement detail the properties of a new broad-spectrum cephalosporin that has activity against MRSA and is, thus, an outstanding candidate for empirical therapy of cSSSIs. The papers included provide data on the in vitro activity, pharmacokinetics and pharmacodynamics as well as the clinical efficacy of ceftaroline fosamil, which is a welcome addition to our therapeutic armamentarium against cSSSIs.     

Extended-spectrum beta-lactamase-producing Enterobacteriaceae in different environments (humans, food, animal farms and sewage)

OBJECTIVES: This study aimed to determine the presence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in different environments. METHODS: Clinical samples and stool samples from animal farms, sewage, human faecal carriers attending the emergency room and faecal carriers in the context of food-borne disease outbreaks were subcultured onto MacConkey agar supplemented with cefotaxime for the detection of ESBL-producing Enterobacteriaceae. Identification, susceptibility pattern and ERIC-PCR were used for clone delineation in each sample. Community consumption of antibiotics was also recorded. RESULTS: An ESBL-producing Enterobacteriaceae prevalence of 1.9% was observed in human infections. A cross-sectional survey of human faecal carriers in the community showed a general prevalence of 6.6% with a temporal distribution. High use of antibiotics in winter coincided with a lower prevalence in carriers. ESBL-producing Enterobacteriaceae were detected in the five samples of human sewage, in samples from 8 of 10 pig farms, 2 of 10 rabbit farms, from all 10 poultry farms and in 3 of 738 food samples studied. Faecal carriage of ESBL-producing Enterobacteriaceae was detected in samples from 19 of 61 food-borne outbreaks evaluated. All food-borne outbreaks were due to enteropathogens. The prevalence of carriers in these outbreaks ranged from 4.4% to 66.6%. CONCLUSIONS: This widespread occurrence of ESBL-producing Enterobacteriaceae suggests that the community could act as a reservoir and that food could contribute to the spread of these strains.     

Occurrence of Extended-Spectrum β-Lactamases in Members of the Family Enterobacteriaceae in Italy: Implications for Resistance to β-Lactams and Other Antimicrobial Drugs

An Italian nationwide survey was carried out to assess the prevalences and the antimicrobial susceptibilities of members of the family Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs). Over a 6-month period, 8,015 isolates were obtained from hospitalized patients and screened for resistance to extended-spectrum cephalosporins and monobactams. On the basis of a synergistic effect between clavulanate and selected beta-lactams (ceftazidime, aztreonam, cefotaxime, cefepime, and ceftriaxone), 509 isolates were found to be ESBL positive (6.3%). Colony blot hybridization with bla(TEM) and bla(SHV) DNA probes allowed one to distinguish four different genotypes: TEM-positive, SHV-positive, TEM- and SHV-positive, and non-TEM, non-SHV ESBL types. MICs for each isolate (E-test) were obtained for widely used beta-lactams, combinations of beta-lactams with beta-lactamase inhibitors, aminoglycosides, and fluoroquinolones. Among ESBL-positive strains, Klebsiella pneumoniae, Proteus mirabilis, and Escherichia coli accounted for 73.6% of isolates. Overall, TEM-type ESBLs were more prevalent than SHV-type enzymes (234 versus 173), whereas the prevalence of strains producing both TEM- and SHV-type ESBLs was similar to that of isolates producing non-TEM, non-SHV enzymes (55 and 38, respectively). In vitro, all but one of the ESBL-producing isolates remained susceptible to imipenem. Susceptibility to other drugs varied: piperacillin-tazobactam, 91%; amoxicillin-clavulanic acid, 85%; cefoxitin, 78%; amikacin, 76%; ampicillin-sulbactam, 61%; ciprofloxacin, 58%; and gentamicin, 56%. Associated resistance to aminoglycosides and ciprofloxacin was observed most frequently among TEM-positive strains. Since therapeutic options for multiresistant Enterobacteriaceae are limited, combinations of beta-lactams and beta-lactamase inhibitors appear to represent an important alternative for treating infections caused by ESBL-producing ENTEROBACTERIACEAE:     

What are the risk factors for recurrent UTI with repeated ESBL-producing Enterobacteriaceae? A retrospective cohort study

IntroductionA previous study has shown that two-thirds of patients with urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae experience recurrence with the same bacteria on subsequent UTI episodes. However, little is known about which patients suffer from UTI due to ESBL-producing Enterobacteriaceae repeatedly. This study aimed to investigate the risk factors for recurrent UTI due to repeated ESBL-producing organism infections.MethodsThis retrospective, single-center, observational cohort study screened all patients with UTI caused by ESBL-producing strains between January 2012 and April 2019. Among the patients who were followed up, patients who experienced UTI recurrence were enrolled and divided into two groups: ESBL recurrence group and non-ESBL recurrence group. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between patient characteristics and the development of recurrent UTI caused by ESBL-producing Enterobacteriaceae.ResultsA total of 330 patients were followed up after the diagnosis of UTI caused by ESBL-producing organisms. Among the patients, 115 (34.8%) experienced UTI recurrence, and 71 (61.7%) of them experienced subsequent recurrent UTI due to ESBL-producing organisms. Patient's age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00–1.04; P = 0.046) and recurrent UTI history (HR, 1.69; 95% CI, 1.05–2.72; P = 0.031) were significantly associated with an increased risk of recurrence with ESBL-producing Enterobacteriaceae.ConclusionThese findings showed that a history of previous frequent UTI recurrence is the risk factor for recurrence of UTI due to repeated ESBL producing Enterobacteriaceae infections.     

Infections with nontyphoidal Salmonella species producing TEM-63 or a novel TEM enzyme, TEM-131, in South Africa

Salmonella spp. producing extended-spectrum beta-lactamases (ESBLs) have been reported in many countries, but there is no information on their prevalence in Africa. ESBL-producing Salmonella enterica serotype Isangi and S. enterica serotype Typhimurium strains have been noted in South Africa since 2001. A total of 160 consecutive isolates of Salmonella spp. were collected from 13 hospitals located in different cities in South Africa over a 5-month period from December 2002 to April 2003. All strains were screened for production of ESBLs by the double disk diffusion test and for AmpC production by assessing resistance to cefoxitin. bla(SHV), bla(TEM), bla(CTX-M), and bla(CMY-2) were sought from all ESBL-positive and cefoxitin-resistant isolates. A total of 15.6% (25 of 160) isolates produced SHV or TEM ESBLs, and 1.9% (3 of 160) produced CMY-2. Nine S. enterica serotype Typhimurium, eight S. enterica serotype Isangi, and three S. enterica serotype Muenchen strains produced either TEM-63 or a derivative of TEM-63 designated TEM-131. Both TEM-63 and TEM-131 have an isoelectric point of 5.6, and their sequences have the following amino acid substitutions compared to the TEM-1 sequence: Leu21Phe, Glu104Lys, Arg164Ser, and Met182Thr. Additionally, TEM-131 has an Ala237Thr substitution. ESBL-producing Salmonella spp. have become a significant public health problem in South Africa with particular implications for the treatment of serious nontyphoidal Salmonella infections in children, for whom extended-spectrum cephalosporins were the preferred treatment.     

Emergence of ArmA and RmtB aminoglycoside resistance 16S rRNA methylases in Belgium

OBJECTIVES: 16S rRNA methylase-mediated high-level resistance to aminoglycosides has been reported recently in clinical isolates of Gram-negative bacilli only from a limited number of countries. This study was conducted to investigate the occurrence of this type of resistance in clinical isolates of Enterobacteriaceae from two Belgian hospitals and the characteristics of the strains. METHODS: We screened for high-level gentamicin, tobramycin and amikacin resistance in clinical isolates of Enterobacteriaceae consecutively collected between 2000 and 2005 at two laboratories by PCR for the armA, rmtA and rmtB 16S rRNA methylase genes. The beta-lactamase presence in the strains was also determined by phenotypic and genotypic methods. RESULTS: Overall armA genes were detected in 18 Klebsiella pneumoniae, Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae and Citrobacter amalonaticus whereas rmtB was detected in a single E. coli isolate. The rmtA gene was not found. All 16S rRNA methylase-bearing strains produced extended-spectrum beta-lactamases (ESBLs), predominantly type CTX-M-3, as well as various types of beta-lactamases. In the majority of the strains, the armA gene was carried by conjugative plasmids of the IncL/M incompatibility group whereas rmtB was borne by an IncFI plasmid. CONCLUSIONS: This is the first report of the emergence of 16S rRNA methylases in Enterobacteriaceae in Belgium. The rapid spread of multidrug-resistant isolates producing both ESBLs and 16S rRNA methylases raises clinical concern and may become a major therapeutic threat in the future.