A longitudinal molecular surveillance of clinical methicillin-resistant Staphylococcus aureus isolates in neonatal units in a teaching hospital, 2003–2018

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) has been an important nosocomial pathogen in our neonatal units since 1990s. To understand the longitudinal changing molecular epidemiology of these MRSA isolates, we conducted this study.MaterialsFrom 2003 to 2018, we collected clinical MRSA isolates from 536 infants hospitalized at neonatal units of a medical center in northern Taiwan. First isolate from each infant was characterized.ResultsThe case/isolate number ranged from 7 cases/isolates (the lowest) in 2010 to 71 cases/isolates (the highest) in 2004. Of the 536 isolates, a total of 15 pulsotypes were identified. Three major clones were identified and characterized as sequence type (ST) 239/pulsotype A/staphylococcal chromosomal cassette (SCC) mec III/Panton-Valentine leukocidin (PVL)-negative, accounting for 22.2% of the isolates, ST59/pulsotype C/SCCmec IV/PVL-negative, accounting for 34.3% and ST59/pulsotype D/SCCmec V_T/PVL-positive, accounting for 30.0%. The first clone (hospital strains) dominated in the first two years, and became weakened from 2005 through 2016. Clonal complex (CC) 59 (combined the second and third clones) dominated (>50% of the isolates) from 2005 through 2018. One community clone (ST573) demonstrated a marked increase since 2007 and vanished abruptly since 2010. Several minor MRSA clones emerged after 2010.ConclusionThe molecular epidemiology of MRSA isolates in our neonatal units from 2003 to 2018 revealed that an epidemic as well as endemic hospital clone of ST239 dominated before 2005 and was replaced by the local community clone of CC59 thereafter.     

A twenty years’ results of the antimicrobial resistance profile and multidrug resistance trend of invasive Streptococcus pneumoniae isolates recovered from adult patients in Turkey: A literature review

PurposeThe aim of this study is to analyze antimicrobial resistance and multidrug (MDR)/extensively (XDR) resistance trend among Streptococcus pneumoniae isolates causing invasive disease in adult patients.MethodsWe analyzed antimicrobial resistance and multidrug resistance trend among invasive S.pneumoniae isolates recovered from adult patients (≥18-years) in a tertiary University Hospital, Turkey between 1996 and 2018. The antibiotic susceptibility pattern was determined by using gradient-test for penicillin and cefotaxime and disk-diffusion method for other antibiotics.ResultsA total of 272 isolates (74.3% from the bloodstream) of S. pneumoniae were collected during the study period. The highest non-susceptibility rate was obtained for tetracycline (63.5%), followed by trimethoprim/sulfamethoxazole (48%), penicillin-oral (30.4%), erythromycin (21.7%), clindamycin (15.8%), ciprofloxacin/levofloxacin (5.9%), penicillin-parenteral (5.5%), cefotaxime (2.2%), and rifampisin (1.8%), respectively. No resistance was observed against vancomycin during the years studied. Over the study period, a significant increase in the rate of antimicrobial resistance among invasive pneumococcal isolates was detected with a peak at period 2014–2018. Although there was an increase in the rates of non-susceptibility to penicillin oral, parenteral penicillin, cefotaxime, erythromycin and clindamycin in adult patients, the results were not statistically significant except erythromycin. Prevalence of MDR and XDR S. pneumoniae were 29% and 9.2% respectively. When the serotypes of MDR isolates were examined, it was noted that serotype 19F (35%) and 14 (12.5%) were the most common.ConclusionsOur study showed an overall increase in non-susceptibility rates of penicillin and erythromycin in invasive S.pneumoniae isolates recovered from Turkish adult patients. Although the prevalence of MDR showed fluctuation between years, the incidence of MDR remained stable. These data indicate the necessity for continuous monitoring and assessment of serotypes and antimicrobial resistance trends in S.pneumoniae in different age groups at both the national and the regional levels as it can be affected by the serotypes dominant in that region, rational use of antibiotics and the vaccination programs.     

emm Types, virulence factors, and antibiotic resistance of invasive Streptococcus pyogenes isolates from Italy: What has changed in 11 years?

To investigate the epidemiology and characteristics of invasive group A streptococcal (GAS) disease over 11 years in Italy, this study compared the emm types and the superantigen toxin genes speA and speC as well as the erythromycin, clindamycin, and tetracycline susceptibilities of 207 invasive GAS strains collected during two national enhanced surveillance periods (1994 to 1996 and 2003 to 2005) and the time between each set of surveillance periods. The present study demonstrated that emm1 strains were consistently responsible for about 20% of invasive GAS infections, while variations in the frequencies of the other types were noted, although the causes of most cases of invasive infections were restricted to emm1, emm3, emm4, emm6, emm12, and emm18. During the 1994 to 1996 surveillance period, an emm89 epidemic clone spread across the northern part of Italy. A restricted macrolide resistance phenotype-type distribution of the bacteriophage-encoded speA toxin as well as of macrolide resistance genes was noted over time. Indeed, the recent acquisition of macrolide resistance in previously susceptible emm types was observed.     

Rapid emergence of daptomycin resistance in clinical isolates of Corynebacterium striatum… a cautionary tale

The objective of this study was to investigate the observation of daptomycin resistance in Corynebacterium striatum, both in vivo and in vitro. We describe a case of C. striatum bacteremia in a patient with a left ventricular assist device (LVAD); the initial isolate recovered was daptomycin susceptible with a minimum inhibitory concentration (MIC) of 0.125 μg/ml. Two months later, and after daptomycin therapy, the individual became bacteremic with an isolate of C. striatum with a daptomycin MIC of >256 μg/ml. To study the prevalence of daptomycin resistance in C. striatum, clinical isolates of C. striatum were grown in broth culture containing daptomycin to investigate the emergence of resistance to this antimicrobial. Molecular typing was used to evaluate serial isolates from the index patient and the clinical isolates of C. striatum we assayed. In vitro analysis of isolates from the index patient and 7 of 11 additional C. striatum isolates exhibited the emergence of high-level daptomycin resistance, despite initially demonstrating low MICs to this antimicrobial agent. This phenotype was persistent even after serial subculture in the absence of daptomycin. Together, these data demonstrate that caution should be taken when using daptomycin to treat high-inoculum infections and/or infections of indwelling medical devices with C. striatum. To our knowledge, this is the first report characterizing the emergence of daptomycin resistance in C. striatum.     

Is nasal carriage of Staphylococcus aureus the main acquisition pathway for surgical-site infection in orthopaedic surgery?

The endogenous or exogenous origin of Staphylococcus aureus, responsible for orthopaedic surgical-site infections (SSI), remains debated. We conducted a multicentre prospective cohort study to analyse the respective part of exogenous contamination and endogenous self-inoculation by S. aureus during elective orthopaedic surgery. The nose of each consecutive patient was sampled before surgery. Strains of S. aureus isolated from the nose and the wound, in the case of SSI, were compared by antibiotypes or pulsed-field gel electrophoresis (PFGE). A total of 3,908 consecutive patients undergoing orthopaedic surgery were included. Seventy-seven patients developed an SSI (2%), including 22 related to S. aureus (0.6%). S. aureus was isolated from the nose of 790 patients (20.2%) at the time of surgery. In the multivariate analysis, S. aureus nasal carriage was found to be a risk factor for S. aureus SSI in orthopaedic surgery. However, only nine subjects exhibiting S. aureus SSI had been found to be carriers before surgery: when compared, three pairs of strains were considered to be different and six similar. In most cases of S. aureus SSI, either an endogenous origin could not be demonstrated or pre-operative nasal colonisation retrieved a strain that was different from the one recovered from the surgical site     

Methicillin-resistant Staphylococcus aureus in HIV patients: Risk factors associated with colonization and/or infection and methods for characterization of isolates – a systematic review

Staphylococcus aureus is an important cause of infections and HIV-infected individuals are frequently susceptible to this pathogen. The aim of this study was to perform a systematic review to identify both the risk factors associated with colonization/infection by methicillin-resistant S. aureus in HIV patients and the methods used for characterization of isolates. An electronic search of articles published between January 2001 and December 2013 was first conducted. Among 116 studies categorized as being at a quality level of A, B or C, only 9 studies were considered to have high methodological quality (level A). The majority of these studies were retrospective (4/9 studies). The risk factors associated with colonization/infection by S. aureus were use of antimicrobials (4/9 studies), previous hospitalization (4/9 studies) and low CD4+ T lymphocyte counts (<200 cells/μl) (3/9 studies). Culture in mannitol salt agar (3/9 studies) and the latex agglutination test (5/9 studies) were the main methods used for bacterial phenotypic identification. Genotypic profiles were accessed by pulsed-field gel electrophoresis (6/9 studies) and USA300 was the most prevalent lineage (5/9 studies). Most isolates were resistant to erythromycin (3/9 studies) and susceptible to vancomycin (4/9 studies). Ultimately, use of antimicrobials and previous hospitalization were the main risk factors for colonization/infection by methicillin-resistant S. aureus in HIV-infected individuals. However, the numbers of evaluated patients, the exclusion and inclusion criteria and the characterization of the S. aureus isolates were not uniform, which made it difficult to establish the characteristics associated with HIV patients who are colonized/infected by S. aureus.     

Panton-Valentine leukocidin–positive Staphylococcus aureus in skin and soft tissue infections from primary care patients

ObjectivesTo characterize deep skin and soft tissue infections (dSSTI) caused by Panton-Valentine leukocidin (PVL)-positive versus PVL-negative Staphylococcus aureus isolates.MethodsWe performed a retrospective analysis of patients' records including S. aureus isolates from outpatients with dSSTI. Samples had been submitted by primary care physicians, i.e. general practitioners, surgeons, dermatologists and paediatricians, located in Berlin, Germany, in 2007–2017. Bacterial isolates were identified and tested for antimicrobial susceptibility by VITEK 2; PVL was detected by PCR.ResultsIn total, 1199 S. aureus isolates from 1074 patients with dSSTI were identified, and 613 (51.1%) of 1199 samples were PVL⁺. The median age of patients with PVL⁺ S. aureus was lower than in patients with PVL− S. aureus (34 years, range 0–88 years, vs. 44 years, range 0–98 years; p < 0.0001). PVL was associated with repeated/multiple samples compared to single sample submission (69/92, 75% vs. 448/982, 45.6%, p < 0.0001; odds ratio (OR), 3.6; 95% confidence interval (CI), 2.2–5.8). Interestingly, the highest PVL positivity rate was found in isolates from gluteal (82/108, 75.9%; OR, 3.6; 95% CI, 2–5) or axillary (76/123, 61.8%; OR, 2; 95% CI, 1.1–3.3) localizations compared to isolates from the arm. The PVL positivity rate did not increase over time. Yet we noticed an increase in the trimethoprim/sulfamethoxazole (SXT) resistance rate in PVL⁺ isolates, mainly methicillin-sensitive S. aureus, when considering SXT resistance rates of 2007–2012 versus 2013–2017 (35/226, 15.5% vs. 74/289, 25.6%; p 0.01).ConclusionsIn outpatients, gluteal and axillary dSSTI are indicative of PVL⁺ S. aureus. Providing SXT as a complementary treatment for dSSTI should be based on susceptibility testing.     

Evaluation of a commercial microarray as a confirmation test for the presence of extended-spectrum β-lactamases in isolates from the routine clinical setting

Since the diagnostic characteristics of the Check-KPC ESBL microarray as a confirmation test on isolates obtained in a routine clinical setting have not been determined, we evaluated the microarray in a random selection of 346 clinical isolates with a positive ESBL screen test (MIC >1 mg/L for cefotaxime or ceftazidime or an ESBL alarm from the Phoenix or Vitek-2 expert system) collected from 31 clinical microbiology laboratories in the Netherlands in 2009. Using sequencing as the reference method the sensitivity of the microarray was 97% (237/245), the specificity 98% (97/99), the positive predictive value 99% (237/239) and the negative predictive value 92% (97/105).     

Methicillin resistance is not a predictor of severity in community-acquired Staphylococcus aureus necrotizing pneumonia—results of a prospective observational study

Staphylococcal necrotizing pneumonia (NP) is a severe disease associated with Panton–Valentine leucocidin (PVL). NP was initially described for methicillin-susceptible Staphylococcus aureus (MSSA) infection, but cases associated with methicillin-resistant S. aureus (MRSA) infection have increased concomitantly with the incidence of community-acquired MRSA worldwide. The role of methicillin resistance in the severity of NP remains controversial. The characteristics and outcomes of 133 patients with PVL-positive S. aureus community-acquired pneumonia (CAP) were compared according to methicillin resistance. Data from patients hospitalized for PVL-positive S. aureus CAP in France from 1986 to 2010 were reported to the National Reference Centre for Staphylococci and were included in the study. The primary end point was mortality. Multivariate logistic modelling and the Cox regression were used for subsequent analyses. We analysed 29 cases of PVL-MRSA and 104 cases of PVL-MSSA pneumonia. Airway haemorrhages were more frequently associated with PVL-MSSA pneumonia. However, no differences in the initial severity or the management were found between these two types of pneumonia. The rate of lethality was 39% regardless of methicillin resistance. By Cox regression analysis, methicillin resistance was not found to be a significant independent predictor of mortality at 7 or 30 days (p 0.65 and p 0.71, respectively). Our study demonstrates that methicillin resistance is not associated with the severity of staphylococcal necrotizing pneumonia.     

Declining drug resistance of Mycobacterium tuberculosis isolates from elderly patients in Taiwan, 2000–2008

We retrospectively investigated the prevalence of drug resistance in Mycobacterium tuberculosis (MTB) isolates recovered from elderly patients and compared the drug resistance patterns between the elderly (≥65 years old) and adult (15–64 years old) patients. Data on the prevalence of drug resistance in clinical and non-duplicate isolates of MTB recovered from 2000 to 2008 were evaluated. Among the 3,186 non-duplicate MTB isolates found during the study period, 1,497 isolates were recovered from elderly patients. Thirty-eight (2.54%) isolates were multidrug-resistant tuberculosis (MDRTB). The rates of resistance to isoniazid (INH), rifampicin (RIF), ethambutol (EMB), streptomycin (SM), ofloxacin, rifabutin, any one drug-resistant (ADR), and multidrug-resistant (MDR) were significantly lower in isolates from the elderly than from adults (p < 0.05). Significant decreasing trends in resistance rates to EMB, SM, at least any one of the four first-line agents (ADR), and MDRTB were observed (p < 0.05) . In conclusion, elderly patients had a lower rate of anti-TB drug resistance than adults and a decreasing overall trend of anti-TB drug resistance was found in the elderly in recent years, but the higher rate of MDRTB in Taiwan continues to present a challenge for the control of TB in the elderly.     

Impact of the European Antimicrobial Resistance Surveillance System on the development of a national programme to monitor resistance in Staphylococcus aureus and Streptococcus pneumoniae in Ireland, 1999–2003

Presented here is the 5-year impact of a national antimicrobial resistance surveillance system in Ireland, which was introduced in accordance with the European Antimicrobial Resistance Surveillance System (EARSS). Participation in EARSS began in Ireland in 1999. Initially, 12 laboratories serving a mix of general and tertiary hospitals participated, but by 2003, participation had increased to 28 laboratories with a population coverage of 89%. During 1999–2003, 4,146 episodes of Staphylococcus aureus bacteraemia were reported, and methicillin resistance was detected in 1,709 (41.2%) of these isolates. Over the same period, 1,245 invasive (blood or cerebrospinal fluid) episodes of Streptococcus pneumoniae infection were reported, and 160 (12.9%) isolates were found to be non-susceptible to penicillin, with 23 (1.8%) demonstrating high-level penicillin resistance. By 2003, most Irish hospitals were participating in EARSS, which has been a catalyst for the development of a national antimicrobial resistance surveillance programme.     

Diversity of carbapenemases in clinical isolates of Enterobacteriaceae in Croatia—the results of a multicentre study

Since the first carbapenem-resistant Klebsiella pneumoniae strain was isolated in 2008, Enterobacteriaceae with reduced susceptibility to one or more carbapenems have emerged sporadically in different geographical regions in Croatia. These observations gave rise to a multicenter study on carbapenem resistance in Enterobacteriaceae from Croatia. Fifty-seven carbapenem-non-susceptible strains of Enterobacteriaceae were collected during 2011–2012 from four large hospital centres in Croatia. Overall, 36 strains produced VIM-1 β-lactamase, three produced NDM-1, and one produced KPC-2. A high degree of clonal relatedness was observed in Enterobacter cloacae and Citrobacter freundii strains, in contrast to K. pneumoniae strains. Bla_VIM genes were located within class1 integron which contained genes encoding resistance to aminoglycosides (aac_A4). The study found strong association between bla_VIM and qnr_B6 and between bla_NDM and qnr_A6 genes.     

Epidemiology and clinical presentation of community-acquired Staphylococcus aureus bacteraemia in children under 5 years of age admitted to the Manhiça District Hospital,Mozambique, 2001–2019

Staphylococcus aureus bacteraemia (SAB) is one of the most common bloodstream infections globally. Data on the burden and epidemiology of community-acquired SAB in low-income countries are scarce but needed to define preventive and management strategies. Blood samples were collected from children < 5 years of age with fever or severe disease admitted to the Manhiça District Hospital for bacterial isolation, including S. aureus. Between 2001 and 2019, 7.6% (3,197/41,891) of children had bacteraemia, of which 12.3% corresponded to SAB. The overall incidence of SAB was 56.1 episodes/100,000 children-years at risk (CYAR), being highest among neonates (589.8 episodes/100,000 CYAR). SAB declined significantly between 2001 and 2019 (322.1 to 12.5 episodes/100,000 CYAR). In-hospital mortality by SAB was 9.3% (31/332), and significantly associated with infections by multidrug-resistant (MDR) strains (14.7%, 11/75 vs. 6.9%, 14/204 among non-MDR, p = 0.043) and methicillin-resistant S. aureus (33.3%, 5/15 vs. 7.6%, 20/264 among methicillin-susceptible S. aureus, p = 0.006). Despite the declining rates of SAB, this disease remains an important cause of death among children admitted to MDH, possibly in relation to the resistance to the first line of empirical treatment in use in our setting, suggesting an urgent need to review current policy recommendations.

     

Susceptibility of European Escherichia coli clinical isolates from intra-abdominal infections,extended-spectrum β-lactamase occurrence,resistance distribution,and molecular characterization of ertapenem-resistant isolates (SMART 2008–2009)

A total of 3160 clinical isolates of Escherichia coli from intra-abdominal infections were collected during 2008–2009 from 13 European countries. The frequency of extended-spectrum β-lactamase (ESBL)-producing isolates in Europe was 11%. The most active antibiotics tested were typically imipenem, ertapenem, and amikacin, although the activity of all non-carbapenem antibiotics was lower when tested against ESBL-positive isolates than when tested against ESBL-negative isolates. Ertapenem exhibited 99.3% susceptibility with all isolates, and 96.8% susceptibility with ESBL-positive isolates. With application of the ertapenem CLSI clinical breakpoint for resistance (MIC ≥1 mg/L), only six isolates (0.2%) were ertapenem-resistant, and only three of these were available for molecular characterization. Of those three, only one was ESBL-positive (CTX-M-14), and two were carbapenemase-positive (OXA-48). All three were negative for, VIM, NDM and KPC carbapenemases. Although the level of ertapenem resistance in E. coli is very low, further monitoring of ertapenem susceptibility and molecular characterization of ertapenem-resistant isolates is needed.     

Evaluation of vancomycin MIC creep in methicillin-resistant Staphylococcus aureus infections—a systematic review and meta-analysis

ObjectivesVancomycin is currently the primary option treatment for methicillin-resistant Staphylococcus aureus (MRSA). However, an increasing number of MRSA isolates with high MICs, within the susceptible range (vancomycin MIC creep), are being reported worldwide. Resorting to a meta-analysis approach, this study aims to assess the evidence of vancomycin MIC creep.MethodsWe searched for studies in the PubMed database. The inclusion criteria for study eligibility included the possibility of retrieving the reported data values of vancomycin MIC and information concerning the applied MIC methodology.ResultsThe mean values of vancomycin MICs, of all 29 234 S. aureus isolates reported in the 55 studies included in the meta-analysis, were 1.23 mg/L (95% CI 1.13–1.33) and 1.20 mg/L (95% CI 1.13–1.28) determined by Etest and broth microdilution method, respectively. No significant differences were observed between these two methodologies. We found negative correlation between pooled mean/pooled proportion and time strata.ConclusionsWe have found no evidence of the MIC creep phenomenon.