Phylogenomic analysis reveals persistence of gonococcal strains with reduced-susceptibility to extended-spectrum cephalosporins and mosaic penA-34.

The recent emergence of strains of Neisseria gonorrhoeae associated with treatment failures to ceftriaxone, the foundation of current treatment options, has raised concerns over a future of untreatable gonorrhea. Current global data on gonococcal strains suggest that several lineages, predominately characterized by mosaic penA alleles, are associated with elevated minimum inhibitory concentrations (MICs) to extended spectrum cephalosporins (ESCs). Here we report on whole genome sequences of 813 N. gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project in the United States. Phylogenomic analysis revealed that one persisting lineage (Clade A, multi-locus sequence type [MLST] ST1901) with mosaic penA-34 alleles, contained the majority of isolates with elevated MICs to ESCs. We provide evidence that an ancestor to the globally circulating MLST ST1901 clones potentially emerged around the early to mid-20th century (1944, credibility intervals [CI]: 1935-1953), predating the introduction of cephalosporins, but coinciding with the use of penicillin. Such results indicate that drugs with novel mechanisms of action are needed as these strains continue to persist and disseminate globally.

Dynamics of extended-spectrum cephalosporin-resistant Escherichia coli in pig farms: A longitudinal study.

OBJECTIVES: Point prevalence estimates of extended-spectrum cephalosporin-resistant Escherichia coli (ESC-R-Ec) are important surveillance measures but may not uncover the ESC-R-Ec dynamics within pig farms. A longitudinal study was therefore performed by sampling individual pigs, pig farmers and the environment. METHODS: On average, 30 (range 10-46) piglets of 31 Swiss farms were sampled during the suckling, weaning and fattening stages (n= 2437 samples). In addition, stool from pig farmers and environmental samples were obtained and metadata collected by questionnaires. ESC-R-Ec was identified by routine culture, and clonal relationships and resistance genes were derived from whole genome sequencing data. RESULTS: Working on pig farms was not associated with an increased prevalence of ESC-R-Ec in humans. ESC-R-Ec prevalence significantly decreased from 6.2% to 3.9% and 1.8% for the suckling, weaned and fattening pigs, respectively (P < 0.001). Within the 57 ESC-R-positive suckling piglets, persisting carriage was detected in 25 animals at two consecutive time points and one animal at three consecutive time points. Clonal spread (n=7 farms, 22.6%) and horizontal gene transfer (n=1 farm, 3%) within pigs but not between humans and animals was detected. Liquid manure (n=10 samples, 16.7%) was identified as the major environmental reservoir of ESC-R-Ec in the pig farm environment. CONCLUSIONS: Pig farming practices like all-in-all-out systems, but not antimicrobial usage, were associated with reduced risk of ESC-R-Ec at the farm level. As carriage duration is normally short within the individual pigs, the risk of recolonisation and clonal spread of ESC-R-Ec might be reduced by applying appropriate decontamination strategies.

Third-Generation Cephalosporin Resistance and Associated Discordant Antibiotic Treatment in Emergency Department Febrile Urinary Tract Infections.

STUDY OBJECTIVE: Third-generation cephalosporin-resistant (3GCR) Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis (EKP) are an increasingly common cause of community-onset urinary tract infections (UTIs) in the United States. The 3GCR antimicrobial resistance pattern in these Enterobacterales species is most commonly due to production of extended-spectrum ß-lactamases. We sought to provide contemporary, emergency department (ED)-focused data on 3GCR-EKP UTI regional prevalence, presentation, antibiotic susceptibility, and empiric treatment patterns, and outcomes. METHODS: We performed a retrospective cohort study of all adults admitted with a febrile UTI at 21 Kaiser Permanente Northern California EDs between January 2017 and June 2019. Inclusion criteria included fever; admitting diagnosis of UTI, pyelonephritis, or sepsis; and ED urine culture with greater than 100,000 colony-forming units/mL of an EKP species. 3GCR was defined as in vitro resistance to ceftriaxone, ceftazidime, or both. 3GCR-EKP cases were compared with non-3GCR-EKP controls for the following: demographics, comorbidities, presenting clinical features, urinary isolate antimicrobial susceptibility, treatment, and clinical outcomes. The primary outcome measure was the rate of discordant initial empiric antibiotic treatment (administered within 6 hours of ED arrival) when compared with antimicrobial susceptibility testing. Secondary outcomes included hospital length of stay and 90-day mortality, adjusted for comorbidities and severity of illness. RESULTS: There were 4,107 patients (median age 73 years and 35% men) who met study inclusion criteria. Of these patients, 530 (12.9%) had a 3GCR-EKP urinary tract infection. The proportion of subjects possessing risk factors for a health care-associated or extended-spectrum ß-lactamase infection was 92.8% of case patients and 86.1% of controls. When comparing 3GCR-EKP case and non-3GCR-EKP control isolates, ciprofloxacin susceptibility rates were 21% versus 88%, and piperacillin/tazobactam susceptibility rates were 89% versus 97%, respectively. Initial empiric antibiotic therapy was discordant with antimicrobial susceptibility testing results in 63% of case patients versus 7% of controls (odds ratio 21.0; 95% confidence interval 16.9 to 26.0). The hospital length of stay was longer for 3GCR-EKP case patients, with an adjusted mean difference of 29.7 hours (95% CI 19.0 to 40.4). Ninety-day mortality was 12% in case patients versus 8% in controls (adjusted odds ratio 1.56; 95% confidence interval 1.07 to 2.28). CONCLUSION: In this large, 2017 to 2019 Northern California ED study, nearly 13% of febrile EKP UTIs requiring hospitalization were caused by 3GCR-EKP, and in these cases, initial empiric therapy was often discordant with antimicrobial susceptibility testing. 3GCR-EKP infections were associated with a longer hospital length of stay and higher 90-day mortality. Similar data from other regions and for outpatient UTIs are needed.

Occurrence of ESBL-Producing Escherichia coli ST131, Including the H30-Rx and C1-M27 Subclones, Among Urban Seagulls from the United Kingdom.

Antimicrobial resistance is a public health concern. Understanding any role that urban seagulls may have as a reservoir of resistant bacteria could be important for reducing transmission. This study investigated fecal Escherichia coli isolates from seagulls (herring gulls and lesser black-backed gulls) to determine the prevalence of extended-spectrum cephalosporin-resistant (ESC-R) and fluoroquinolone-resistant E. coli among gull species from two cities (Taunton and Birmingham) in the United Kingdom (UK). We characterized the genetic background and carriage of plasmid-mediated resistance genes in extended-spectrum ß-lactamase (ESBL)-producing E. coli obtained from these birds. Sixty ESC-R E. coli isolates were obtained from 39 seagulls (39/78, 50%), of which 28 (28/60, 46.7%) were positive for plasmid-mediated CTX-M and/or AmpC ß-lactamase resistance genes. Among these, blaCTX-M-15, blaCTX-M-14, and blaCMY-2 predominated. Three isolates belonging to the B2-ST131 clone were detected, of which two harbored blaCTX-M-15 (typed to C2/H30Rx) and one harbored blaCTX-M-27 and was typed to C1/H30-R (recently described as the C1-M27 sublineage). The plasmid-mediated quinolone resistance (PMQR) gene carriage prevalence (11.7%) consisted of aac(6')-Ib-cr and qnrB genes. No carbapenem or colistin resistance genes were detected. Urban seagulls in the UK are colonized and can spread major antimicrobial-resistant E. coli isolates harboring ESBL and PMQR determinants, including clinically important strains such as the pandemic clone B2-ST131 and the C1-M27 subclade. This is the first report of ST131-C1-M27 subclade in wildlife in the UK and in seagulls worldwide.

Prior exposure of agriculture cephalosporin ceftiofur impaired conjugation of blaCTX-M-65 gene-bearing plasmid in Salmonella Saintpaul.

AIMS: Although a link between agricultural cephalosporin use and resistance in Salmonella has been demonstrated with the drug ceftiofur, the underlying mechanism of the correlation is unclear. This study investigated the impact of ceftiofur exposure in S. Saintpaul on ceftriaxone resistance, the gene expression and the conjugative transfer of the blaCTX-M-65 gene. METHODS AND RESULTS: Prior ceftiofur exposure caused a twofold increase in MIC from 1024 to 2048 µg ml-1 towards ceftriaxone and increased the enzymatic activity of BlaCTX-M-65 2·2 folds from 3·46 to 7·67 nmol nitrocefin hydrolysed min-1 . A threefold upregulation in gene expression of the blaCTX-M-65 gene was also observed. Donors exposed to ceftiofur subsequently demonstrated a 2·5-fold decrease in transfer efficiency. CONCLUSIONS: Prior exposure of S. Saintpaul to ceftiofur led to increased phenotypic resistance towards ceftriaxone while its ability to spread the cephalosporin resistance through conjugation, conversely, was impaired. SIGNIFICANCE AND IMPACT OF THE STUDY: Findings from this study shed light on one possible mechanism in which agricultural cephalosporin exposure in Salmonella may subsequently impact clinical treatment. The finding that cephalosporin exposure in donors may hinder the subsequent spread of resistance instead of aiding it up was counter-intuitive.

Resistencia de Staphylococcus aureus frente a cefalosporinas en la sepsis neonatal y puerperal / Staphylococcus Aureus Resistance against Cephalosporins in Neonatal and Puerperal Sepsis

Introducción: El mecanismo más común de actividad antibiótica es la interferencia en la síntesis de la pared celular bacteriana. Las cefalosporinas tienen el mismo mecanismo de acción que las penicilinas; sin embargo, tienen un espectro antibacteriano más amplio, son resistentes a muchas b-lactamasas y tienen propiedades farmacocinéticas mejoradas. Objetivos: Identificar por servicios los gérmenes aislados y determinar la resistencia del Staphylococcus aureus a las cefalosporinas. Método: Se realizó un estudio retrospectivo, transversal y descriptivo en hospital Ginecobstétrico de Guanabacoa desde enero de 2014 hasta diciembre de 2016. Se seleccionaron como variables los gérmenes aislados y el patrón de resistencia del germen que predominó frente a todas las generaciones de cefalosporinas. Resultados: En el servicio de neonatología el mayor aislamiento fue en el hemocultivo seguido del catéter venoso (19 pacientes) y tubo endotraqueal. En el servicio de Obstetricia, los loquios y el sitio quirúrgico fue donde se aisló mayor número (69 y 31 pacientes, respectivamente). Conclusiones: El germen más frecuente aislado en ambos servicios fue el Staphylococcus aureus y la resistencia a las cefalosporinas fue muy elevado(AU)

Introduction: The synthesis interference of bacterial cell wall is the most common antibiotic mechanism. Cephalosporins have the same mechanism of action as penicillin. However, they have wider antibacterial spectrum, they are more resistant to B-lactamases and better pharmacokinetics properties. Additionally, cephalosporins have higher activity in front of gram-negative bacteria than penicillin. Objective: To identify isolated germs in these services and to determine the Staphylococcus aureus resistance to cephalosporins. Method: A retrospective, transversal and descriptive study was conducted in Guanabacoa Gynecobstetric hospital from January 2014 to December 2016. selected variables as isolated microorganism, and resistance pattern in front of cephalosporin generations. The isolated germs and the resistance pattern of the germ that prevailed against all generations of cephalosporins were selected as variables. In the Obstetrics Service, the largest number of germs was isolated in the lochia and surgical sites. (69 and 31, respectively). Results: In neonatology service, the most frequent isolation occurred in blood culture (35), venous catheter (19) and endotracheal tube (10). In Obstetric service, the most frequent isolation occurred in liquors (69) and the surgical site isolated (31). Conclusions: Staphylococcus Aureus was the main microorganism isolated in hospital and its cephalosporin resistance was very high(AU)

The role of extended-spectrum cephalosporin-resistance in recurrent community-onset Enterobacteriaceae urinary tract infections: a retrospective cohort study.

BACKGROUND: Bacterial resistance to first line antibiotics used to treat community-onset urinary tract infections (UTIs) continues to emerge. We sought to determine the association between extended-spectrum cephalosporin resistance (ESC-R) and recurrence among Enterobacteriaceae (EB) UTIs. METHODS: A retrospective cohort study was performed. All patients presenting to the Emergency Departments (EDs) or outpatient practices in a large health system with EB UTIs between 2010 and 2013 were included. Exposed patients had ESC-R EB UTIs. Unexposed patients had ESC-susceptible EB UTIs and were matched to exposed patients 1:1 on study year. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between ESC-R EB UTI and time to recurrent UTI within 12 months. RESULTS: A total of 302 patients with an index community-onset EB UTI were included, with 151 exposed and 151 unexposed. Overall, 163 (54%) patients experienced a recurrent UTI with a median time to recurrence of 69 days (interquartile range 25-183). On multivariable analyses, ESC-resistance was associated with an increased hazard of recurrent UTI (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.01-1.91, P = 0.04). Other variables that were independently associated with recurrence included a history of UTI prior to the index UTI and presence of a urinary catheter at the time of the index UTI. Secondarily, we found that when the treatment for the index UTI was adjusted for, there was no longer a significant association between ESC-R status and time to recurrent UTI (aHR 1.26, 95% CI 0.91-1.76, P = 0.17). CONCLUSIONS: Community-onset UTI due to EB demonstrating ESC-resistance is associated with a significantly increased hazard of recurrent UTI within 12 months compared to ESC-susceptible EB, even after adjusting for baseline factors that predispose patients to UTI recurrence. This association appears to be driven primarily by delayed or inappropriate treatment for the index ESC-R EB UTI.

Evaluation of Susceptibilities to Carbapenems and Faropenem Against Cephalosporin-Resistant Neisseria gonorrhoeae Clinical Isolates with penA Mosaic Alleles.

Neisseria gonorrhoeae is a principal pathogen for sexually transmitted infections, especially for male urethritis. Currently, the prevalence of multidrug resistance is increasing. Carbapenems are broad-spectrum antimicrobials that are widely used in the clinical setting, especially for multidrug-resistant Gram-negative bacteria. However, susceptibility to carbapenems has not been well evaluated for cephalosporin-resistant N. gonorrhoeae isolates. In this study, we determined the susceptibility to a series of carbapenems (meropenem, imipenem, doripenem, and biapenem) and faropenem against cephalosporin-resistant (resistant to cefixime, but susceptible to ceftriaxone) and cephalosporin-susceptible N. gonorrhoeae clinical isolates. The gene mutations associated with ß-lactam resistance were evaluated. All cephalosporin-resistant N. gonorrhoeae isolates possessed mosaic mutation alleles in penA (NG-STAR penA-10.001, 27.001, or 108.001). They exhibited a low minimum inhibitory concentration (MIC) (≤0.125 mg/L) for meropenem and markedly high MICs (0.5-2 mg/L) for other carbapenems and faropenem. The strongest association was observed between the mosaic alleles in penA and decreased susceptibility to carbapenems and faropenem compared with mutations in mtrR, porB, and ponA. These results suggest that meropenem may serve as an alternative therapeutic agent for cephalosporin-resistant N. gonorrhoeae with a mosaic allele in penA, whereas other carbapenems and faropenem may be ineffective.

ESCMID-EUCIC clinical guidelines on decolonization of multidrug-resistant Gram-negative bacteria carriers

The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings. Methods: These evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporinresistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same timepoints and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations.

Antimicrobial resistance of Neisseria gonorrhoeae in Germany: low levels of cephalosporin resistance, but high azithromycin resistance.

BACKGROUND: The widespread antimicrobial resistance of Neisseria gonorrhoeae is a serious problem for the treatment and control of gonorrhoea. Many of the previously effective therapeutic agents are no longer viable. Because N. gonorrhoeae infections are not reportable in Germany, only limited data on disease epidemiology and antimicrobial susceptibility patterns are available. The Gonococcal Resistance Network (GORENET) is a surveillance project to monitor trends in the antimicrobial susceptibility of N. gonorrhoeae in Germany in order to guide treatment algorithms and target future prevention strategies. METHODS: Between April 2014 and December 2015, data on patient-related information were collected from laboratories nationwide, and susceptibility testing was performed on 537 N. gonorrhoeae isolates forwarded from the network laboratories to the Conciliar Laboratory for gonococci. Susceptibility results for cefixime, ceftriaxone, azithromycin, ciprofloxacin and penicillin were defined according to EUCAST 4.0 standards. Percentages, medians and interquartile ranges (IQR) were calculated. RESULTS: Altogether, 90% of isolates were from men. The median age was 32 (IQR 25-44) years for men and 25 (IQR 22-40) years for women (p-value < 0.001). The most frequently tested materials among men were urethral (96.1%) and rectal swabs (1.7%), and among women, it was mainly endocervical and vaginal swabs (84.3%). None of the isolates were resistant to ceftriaxone. Furthermore, 1.9% (in 2014) and 1.4% (in 2015) of the isolates were resistant to cefixime, 11.9% and 9.8% showed resistance against azithromycin, 72.0% and 58.3% were resistant to ciprofloxacin, and 29.1% and 18.8% were resistant to penicillin. CONCLUSIONS: Resistance to ceftriaxone was not detected, and the percentage of isolates with resistance to cefixime was low, whereas azithromycin resistance showed high levels during the observation period. The rates of ciprofloxacin resistance and penicillin resistance were very high across Germany. Continued surveillance of antimicrobial drug susceptibilities for N. gonorrhoeae remains highly important to ensure efficient disease management.

Genotypic and epidemiologic characterization of extended-spectrum cephalosporin resistant Salmonella enterica from US beef feedlots.

In the US, nontyphoidal Salmonellae are a common foodborne zoonotic pathogen causing gastroenteritis. Invasive Salmonella infections caused by extended-spectrum cephalosporin resistant (ESCR) phenotypes are more likely to result in treatment failure and adverse health outcomes, especially in severe pediatric Salmonella infections where the extended-spectrum ß-lactams are the therapy of choice. To examine the genetic and epidemiologic characteristics of ESCR Salmonellae which may enter the food chain, we characterized 44 ceftiofur-resistant Salmonella isolates from the National Animal Health Monitoring System (NAHMS) 2011 beef cattle feedlot health and management study. As part of the NAHMS Feedlot 2011 study, 5050 individual fecal samples from 68 large (1000+ head capacity) feedlots were cultured for Salmonella spp. The resulting 460 positive samples yielded 571 Salmonella isolates with 44 (8%) expressing an AmpC ß-lactamase phenotype. These phenotypic blaCMY-2Salmonella isolates represented 8 serotypes, most commonly S. Newport (n=14, 32%), S. Typhimurium (n=13, 30%), and S. Reading (n=5, 11%), followed by S. Dublin, S. Infantis, S. Montevideo, S. Rough O:i;v:1;7, and S. Uganda. Carriage of the blaCMY-2 gene was confirmed for all isolates expressing an AmpC ß-lactamase phenotype by PCR. Additionally, all 44 isolates were shown to carry the blaCMY-2 gene on a large IncA/C plasmid, a gene/plasmid combination which has been previously reported in multiple species. Other plasmids, including IncN, FIC, and FIIA, were also detected in some isolates. Cattle fed chlortetracycline were less likely to be positive for a blaCMY-2Salmonella isolate in their enteric flora compared to those not receiving chlortetracycline during the feeding period. Carriage of blaCMY-2 was more prevalent in Salmonella isolates originating from lighter weight cattle, cattle fed tylosin and dairy breeds. Our characterization of the NAHMS Feedlot 2011 study Salmonella isolates with ESCR phenotype shows that while other cephalosporin resistance mechanisms have been reported in US cattle, specific serotypes harboring blaCMY-2 on IncA/C plasmids may be the dominant resistance genotype.

Overall Low Extended-Spectrum Cephalosporin Resistance but high Azithromycin Resistance in Neisseria gonorrhoeae in 24 European Countries, 2015.

BACKGROUND: Surveillance of Neisseria gonorrhoeae antimicrobial susceptibility in Europe is performed through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), which additionally provides data to inform the European gonorrhoea treatment guideline; currently recommending ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. We present antimicrobial susceptibility data from 24 European countries in 2015, linked to epidemiological data of patients, and compare the results to Euro-GASP data from previous years. METHODS: Antimicrobial susceptibility testing by MIC gradient strips or agar dilution methodology was performed on 2134 N. gonorrhoeae isolates and interpreted using EUCAST breakpoints. Patient variables associated with resistance were established using logistic regression to estimate odds ratios (ORs). RESULTS: In 2015, 1.7% of isolates were cefixime resistant compared to 2.0% in 2014. Ceftriaxone resistance was detected in only one (0.05%) isolate in 2015, compared with five (0.2%) in 2014. Azithromycin resistance was detected in 7.1% of isolates in 2015 (7.9% in 2014), and five (0.2%) isolates displayed high-level azithromycin resistance (MIC ≥ 256 mg/L) compared with one (0.05%) in 2014. Ciprofloxacin resistance remained high (49.4%, vs. 50.7% in 2014). Cefixime resistance significantly increased among heterosexual males (4.1% vs. 1.7% in 2014), which was mainly attributable to data from two countries with high cefixime resistance (~11%), however rates among men-who-have-sex-with-men (MSM) and females continued to decline to 0.5% and 1%, respectively. Azithromycin resistance in MSM and heterosexual males was higher (both 8.1%) than in females (4.9% vs. 2.2% in 2014). The association between azithromycin resistance and previous gonorrhoea infection, observed in 2014, continued in 2015 (OR 2.1, CI 1.2-3.5, p < 0.01). CONCLUSIONS: The 2015 Euro-GASP sentinel system revealed high, but stable azithromycin resistance and low overall resistance to ceftriaxone and cefixime. The low cephalosporin resistance may be attributable to the effectiveness of the currently recommended first-line dual antimicrobial therapy; however the high azithromycin resistance threatens the effectiveness of this therapeutic regimen. Whether the global use of azithromycin in mono- or dual antimicrobial therapy of gonorrhoea is contributing to the global increases in azithromycin resistance remains to be elucidated. The increasing cefixime resistance in heterosexual males also needs close monitoring.

Real-Time PCR Targeting the penA Mosaic XXXIV Type for Prediction of Extended-Spectrum-Cephalosporin Susceptibility in Clinical Neisseria gonorrhoeae Isolates.

Neisseria gonorrhoeae isolates with decreased susceptibility to extended-spectrum cephalosporins (ESCs) are increasing. We developed an assay to predict N. gonorrhoeae susceptibility to ESCs by targeting penA mosaic XXXIV, an allele prevalent among U.S. isolates with elevated ESC MICs. The assay was 97% sensitive and 100% specific for predicting at least one ESC MIC above the CDC alert value among clinical isolates, and it could be multiplexed with a previously validated gyrA PCR to predict ciprofloxacin susceptibility.

Emergence and Spread of Neisseria gonorrhoeae Isolates With Decreased Susceptibility to Extended-Spectrum Cephalosporins in Argentina, 2009 to 2013.

BACKGROUND: The emergence of Neisseria gonorrhoeae strains with decreased susceptibility to cephalosporins represents a major concern globally. The aim of this study was to examine the phenotypic and molecular characteristics of N. gonorrhoeae isolates with decreased susceptibility to ceftriaxone and cefixime in Argentina. METHODS: A total of 1987 isolates were collected during 2009 and 2013. The susceptibility to penicillin G, tetracycline, ciprofloxacin, cefixime, ceftriaxone, and azithromycin was determined using the agar dilution method. The major extended-spectrum cephalosporin resistance determinants (penA, mtrR, and porB1b) were sequenced in 42 N. gonorrhoeae isolates that showed decreased susceptibility to ceftriaxone (minimum inhibitory concentration [MIC], 0.06-0.125 mg/L) and cefixime (MIC, 0.125-0.25 mg/L). Genotyping by N. gonorrhoeae multiantigen sequence typing (NG-MAST) was performed. RESULTS: Between 2009 and 2013, there was a shift in the modal MICs for ceftriaxone. Among the 42 isolates exhibiting decreased susceptibility to ceftriaxone and cefixime, 95.2% were resistant to penicillin G, 95.2% to tetracycline, 97.6% to ciprofloxacin, and 33.3% to azithromycin. Thirty-five (83.3%) of the 42 isolates had a mosaic penA allele XXXIV, which has been previously associated with resistance to ceftriaxone and cefixime as well as treatment failures. The isolates that contained the mosaic penicillin-binding protein 2 (PBP2) XXXIV were associated with NG-MAST ST1407 or closely related genotypes. CONCLUSIONS: In Argentina, N. gonorrhoeae isolates with decreased susceptibility to cefixime and ceftriaxone have now emerged, mostly due to the introduction of the internationally spread multidrug-resistant NG-MAST ST1407.

First Report of Group CTX-M-9 Extended Spectrum Beta-Lactamases in Escherichia coli Isolates from Pediatric Patients in Mexico.

The aim of this study was to identify the presence of group CTX-M-9 extended spectrum beta-lactamases (ESBL) in clinical Escherichia coli isolates from pediatric patients. A total of 404 non-repeated positive ESBL E. coli isolates were collected from documented clinical infections in pediatric patients over a 2-year period. The identification and susceptibility profiles were determined using an automated system. Isolates that suggested ESBL production based on their resistance profiles to third and fourth generation cephalosporin and monobactam were selected. ESBL production was phenotypically confirmed using a diffusion method with cefotaxime and ceftazidime discs alone and in combination with clavulanic acid. blaESBL gene identification was performed through PCR amplification and sequencing. Pulsed Field Gel Electrophoresis (PFGE) and Multilocus Sequence Typing (MLST) were performed to establish the clonal relationships of the E. coli isolates. CTX-M-9-type ESBLs were detected in 2.5% of the isolates. The subtypes corresponded to blaCTX-M-14 (n = 4) and blaCTX-M-27 (n = 6). Additionally, coexistence with other beta-lactamases was observed. A clonal relationship was established in three isolates; the rest were classified as non-related. We found seven different sequence type (ST) in CTX-M-9- producing E. coli isolates. ST38 was the most frequent. This study is the first report in Mexico to document the presence of group CTX-M-9 ESBLs in E. coli isolates from pediatric patients.

Genetic Characterization of a blaVEB-2-Carrying Plasmid in Vibrio parahaemolyticus.

This report describes the first detection of a blaVEB-2 gene in a Vibrio parahaemolyticus strain isolated from a shrimp sample. The blaVEB-2 gene was carried on a novel Inc-type plasmid that was likely to have originated from aquatic organisms, as indicated by a comparison with other known genetic elements in the GenBank database. However, the plasmid contains resistance elements usually harbored by members of the family Enterobacteriaceae, suggesting that gene transfer events occurred and contributed to the formation of this multidrug resistance-encoding plasmid.

Molecular Characterization of Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae from Wild Kelp Gulls in South America.

Extended-spectrum-cephalosporin-resistant Enterobacteriaceae are a public health concern due to limited treatment options. Here, we report on the occurrence and the molecular characteristics of extended-spectrum-cephalosporin-resistant Enterobacteriaceae recovered from wild birds (kelp gulls). Our results revealed kelp gulls as a reservoir of various extended-spectrum cephalosporinase genes associated with different genetic platforms. In addition, we report for the first time the presence of a known epidemic clone of Salmonella enterica serotype Heidelberg (JF6X01.0326/XbaI.1966) among wild birds.

IncI1 Plasmids Carrying Various blaCTX-M Genes Contribute to Ceftriaxone Resistance in Salmonella enterica Serovar Enteritidis in China.

Resistance to extended-spectrum ß-lactams in Salmonella, in particular, in serotypes such as Salmonella enterica serovar Enteritidis that are frequently associated with clinical infections, is a serious public health concern. In this study, phenotypic characterization of 433 clinical S. Enteritidis strains obtained from a nationwide collection of the Chinese Center for Disease Control and Prevention during the period from 2005 to 2010 depicted a trend of increasing resistance to ceftriaxone from 2008 onwards. Seventeen (4%) of the strains were found to be resistant to ceftriaxone, 7% were found to be resistant to ciprofloxacin, and 0.7% were found to be resistant to both ciprofloxacin and ceftriaxone. Most of the ceftriaxone-resistant S. Enteritidis strains (15/17) were genetically unrelated and originated from Henan Province. The complete sequence of an IncI1 plasmid, pSE115, which belonged to a novel sequence type, was obtained. This 87,255-bp IncI1 plasmid was found to harbor a blaCTX-M-14 gene in a novel multidrug resistance region (MRR) within the tra locus. Although the majority of strains were also found to contain conjugative IncI1 plasmids with a size similar to that of pSE115 (∼90 kb) and harbor a variety of blaCTX-M group 1 and group 9 elements, the novel MRR site at the tra locus in pSE115 was not detectable in the other IncI1 plasmids. The findings from this study show that cephalosporin resistance in S. Enteritidis strains collected in China was mainly due to the dissemination of IncI1 plasmids carrying blaCTX-M, resembling the situation in which IncI1 plasmids serve as major vectors of blaCTX-M variants in other members of the Enterobacteriaceae.

Antimicrobial resistance and management of invasive Salmonella disease.

Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20-30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50-75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries.