Meticillin-susceptible Staphylococcus Aureus Research Articles

Meticillin-susceptible Staphylococcus aureus transmission among healthcare workers, patients and the environment in a large acute hospital under non-outbreak conditions investigated using whole-genome sequencing

The role of meticillin-susceptible Staphylococcus aureus (MSSA) colonization of healthcare workers (HCWs), patients and the hospital environment in MSSA transmission events (TEs) is poorly understood. The role of meticillin-resistant Staphylococcus aureus (MRSA) was investigated recently under non-outbreak conditions in a large hospital with a history of endemic MRSA over 2 years using whole-genome sequencing (WGS). Numerous potential MRSA TEs were identified. The present study investigated MSSA TEs from the same sources during the same 2-year hospital study. HCW (N=326) and patient (N=388) volunteers on nine wards were tested for nasal and oral MSSA colonization over 2 years. Near-patient environment (N=1164), high-frequency touch sites (N=810) and air (N=445) samples were screened for MSSA. Representative MSSA and clinical isolates were sequenced and analysed by core genome multi-locus sequence typing. Closely related isolates (≤24 allelic differences) were segregated into related isolate groups (RIGs). Potential TEs involving MSSA in RIGs from HCWs, patients and patient infections were identified in combination with epidemiological data. In total, 635 MSSA were recovered: clinical isolates (N=82), HCWs (N=170), patients (N=120), and environmental isolates (N=263). Twenty-four clonal complexes (CCs) were identified among 406/635 MSSA sequenced, of which 183/406 segregated into 59 RIGs. Numerous potential HCW-to-patient, HCW-to-HCW and patient-to-patient TEs were identified, predominantly among CC5-MSSA, CC30-MSSA and CC45-MSSA. HCW, patient, clinical and environmental isolates were identified in 33, 24, six and 32 RIGs, respectively, with 19/32 of these containing MSSA related to HCW and/or patient isolates. WGS detected numerous potential hospital MSSA TEs involving HCWs, patients and environmental contamination under non-outbreak conditions.

Effects of antibiotics on biofilm and unattached cells of a clinical Staphylococcus aureus isolate from bone and joint infection.

Treatment of orthopaedic infections remains challenging owing to the inability of antibiotics to eradicate biofilms and prevent their regrowth. The present study characterized the effects of 12 antibiotics on in vitro biofilm formed by a representative strain of meticillin-susceptible Staphylococcus aureus (MSSA) isolated from a bone infection. Determination of the minimum biofilm eradication concentrations indicated that in vitro eradication of 24 h-old biofilms required concentrations up to 51,200 times higher than MICs. The influence of the same panel of antibiotics was also investigated on biofilm formation at concentrations including the breakpoints, by numbering viable cells in the suspensions (individual cells) and the biofilm biomass. Except for fusidic acid, the presence of antibiotics during the initial steps of biofilm formation resulted in significant decreases in the number of sessile viable bacteria at the highest concentrations tested. Ceftarolin, daptomycin, fosfomycin, gentamicin, ofloxacin, rifampicin and vancomycin were the most effective drugs. Confocal microscopy analysis indicated that daptomycin was more efficient at bacteria lysis than gentamicin and vancomycin. However, viable individual cells were still detectable in the assays performed with ceftarolin, fosfomycin, ofloxacin, rifampicin and vancomycin at concentrations for which no sessile cells were detected. Although none of the molecules tested was effective at classical therapeutic concentrations against 24 h-old MSSA biofilms, all except fusidic acid were able to impair biofilm formation at concentrations near the breakpoints. However, presence of viable individual unattached cells could imply a significant risk of microbial dissemination and increased risk of infections.

Daptomycin combinations as alternative therapies in experimental foreign-body infection caused by meticillin-susceptible Staphylococcus aureus

Whilst levofloxacin (LVX) in combination with rifampicin (RIF) is considered the optimal treatment for prosthetic joint infection (PJI) caused by meticillin-susceptible Staphylococcus aureus (MSSA), no therapeutic alternatives have been accurately evaluated. Based on the high effectiveness of the combination of daptomycin (DAP) plus RIF against meticillin-resistant S. aureus (MRSA) in this setting, in this study the efficacy of DAP+RIF and DAP+LVX combinations was tested as alternative therapies for foreign-body infections (FBIs) caused by MSSA. A tissue-cage infection model was performed using an MSSA strain. Male Wistar rats were treated for 7 days with LVX, DAP, RIF or the combinations LVX+RIF, DAP+RIF and DAP+LVX. Antibiotic efficacy was evaluated by bacterial counts from tissue cage fluid (TCF) and the cure rate was determined from adhered bacteria. Resistance was screened. Monotherapies were less effective than combinations (P<0.05), and resistance to DAP and RIF emerged. DAP+RIF (decrease in bacterial counts in TCF, −4.9logCFU/mL; cure rate, 92%) was the most effective therapy (P<0.05). There were no differences between LVX+RIF (−3.4logCFU/mL; 11%) and DAP+LVX (−3.3logCFU/mL; 47%). No resistant strains appeared with combined therapies. In conclusion, the combinations DAP+RIF and DAP+LVX showed good efficacy and prevented resistance. DAP+RIF provided higher efficacy than LVX+RIF. These DAP combinations were efficacious alternatives therapies for MSSA FBI. Further studies should confirm whether DAP+RIF may be useful as a first-line therapy in the setting of PJI caused by MSSA.

P106 Comparing susceptibility profiles of antibiotics by contour interval analysis: Ceftaroline and Belgian Streptococcus pneumoniae (SP) and MRSA isolates

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a novel cephalosporin exhibiting bactericidal activity in vitro against Gram-positive organisms, including meticillin-susceptible Staphylococcus aureus (MSSA), meticillin-resistant S. aureus (MRSA), β-haemolytic streptococci, viridans group streptococci (VGS) and Streptococcus pneumoniae, as well as against many common Gram-negative organisms. The objective of this study was to determine the spectrum and potency of ceftaroline against recent (2010) leading pathogens causing complicated skin and soft-tissue infections (cSSTIs) isolated in Europe. A total of 2438 isolates from the Assessing Worldwide Antimicrobial Resistance and Evaluation (AWARE) programme were identified as cSSTI pathogens. Isolates were collected from patients in 52 medical centres in 19 European countries. Reference susceptibility testing for ceftaroline and commonly used antimicrobials was performed by broth microdilution methodologies. Ceftaroline was very active overall against S. aureus (MIC50/90 = 0.25/1 mg/L) and inhibited 100.0% of isolates at a MIC of ≤2 mg/L. Activity against MRSA was documented (MIC50/90 = 1/2 mg/L) but was lower than that observed against MSSA (MIC50/90 = 0.25/0.25 mg/L). Ceftaroline was also very active against 460 β-haemolytic streptococci and 93 VGS (MIC90 = 0.015 mg/L and 0.06 mg/L, respectively). Ceftaroline was active against Escherichia coli (MIC50 = 0.12 mg/L) and Klebsiella pneumoniae (MIC50 = 0.06 mg/L) not expressing extended-spectrum β-lactamases, with activity similar to ceftriaxone and ceftazidime. In summary, this study documents the potent in vitro activity of ceftaroline when tested against recent pathogens isolated from patients with cSSTI in Europe.

Thirty-day mortality in UK patients with community-onset and hospital-acquired meticillin-susceptible Staphylococcus aureus bacteraemia

The difference in mortality between patients with community-onset and hospital-acquired Staphylococcus aureus infections has rarely been described and where it has, results have been conflicting. To determine 30-day mortality in consecutive patients with meticillin-susceptible Staphylococcus aureus (MSSA) bacteraemia and the association between community-onset infection and outcome. From August 2007 to July 2011, demographic, clinical and microbiological data were prospectively collected on patients with MSSA bacteraemia. Patients were followed until death, hospital discharge or recovery from infection. Multivariate logistic regression was used to determine the association between community-onset infection and 30-day mortality. A total of 403 bacteraemic episodes occurred in 392 patients. Overall, there were 44 deaths (11.2%; 95% confidence interval: 7.9-14.0%) at 7 days and 101 deaths (25.8%; 21.5-30.4%) at 30 days. The difference in 30-day mortality between patients with community-onset and hospital-acquired infection was 71/256 (27.7%) versus 31/147 21.1%). Community-onset infection more frequently caused infective endocarditis (13/14, 92.9%), vertebral osteomyelitis (12/13, 92.3%) and skin and soft tissue infection (61/71, 85.9%) whereas intravascular catheter-associated infections were predominantly hospital-acquired (60/82, 73.2%). Age, Pitt score, Charlson comorbidity index (CCI), specific sites of infection (skin and soft tissue, lower respiratory tract and peripheral joints) and delay in appropriate treatment were strongly associated with 30-day mortality. In multivariate analysis, after adjustment for age, CCI and delay in appropriate treatment, community-onset infection was strongly associated with 30-day mortality (odds ratio: 1.59; 95% confidence interval: 0.91-2.80). Compared with hospital-acquired MSSA bacteraemic infection, community-onset infection was associated with worse 30-day outcomes. Hospital-acquired MSSA bacteraemic infections were rarely metastatic, frequently associated with medical devices and patients had better outcomes.

Effect of habituation to tea tree (Melaleuca alternifolia) oil on the subsequent susceptibility of Staphylococcus spp. to antimicrobials, triclosan, tea tree oil, terpinen-4-ol and carvacrol

The aim of this study was to seek additional data on the antimicrobial susceptibility of Staphylococcus spp. after habituation to low levels of the topical antimicrobial agent tea tree (Melaleuca alternifolia) oil. Meticillin-susceptible Staphylococcus aureus (MSSA), meticillin-resistant S. aureus (MRSA) and coagulase-negative staphylococci (CoNS) were habituated to 0.075% tea tree oil for 3 days. Subsequently, the susceptibility of five isolates each of MSSA, MRSA and CoNS to fusidic acid, mupirocin, chloramphenicol, linezolid and vancomycin was determined by Etest, and susceptibility to tea tree oil, terpinen-4-ol, carvacrol and triclosan was determined by agar dilution. Following habituation to 0.075% tea tree oil, antimicrobial MICs differed between control and habituated isolates on 33 occasions (out of a possible 150), with MICs being higher in habituated isolates on 22 occasions. Using clinical breakpoint criteria, one MSSA isolate changed susceptibility category from vancomycin-susceptible (MIC=2μg/mL) to intermediate susceptibility (MIC=3μg/mL) after habituation in one of two replicates. For the non-antibiotic antimicrobial agents, MICs of habituated and control isolates differed on 12 occasions (out of a possible 120); 10 occasions in MRSA and 2 occasions in MSSA. MICs were higher for habituated isolates on five occasions. However, all the differences were one serial dilution only and were not regarded as significant. Habituation to sublethal concentrations of tea tree oil led to minor changes in MICs of antimicrobial agents, only one of which may have been clinically relevant. There is no evidence to suggest that tea tree oil induces resistance to antimicrobial agents.

Spectrum and potency of ceftaroline tested against leading pathogens causing skin and soft-tissue infections in Europe (2010)

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a novel cephalosporin exhibiting bactericidal activity in vitro against Gram-positive organisms, including meticillin-susceptible Staphylococcus aureus (MSSA), meticillin-resistant S. aureus (MRSA), β-haemolytic streptococci, viridans group streptococci (VGS) and Streptococcus pneumoniae, as well as against many common Gram-negative organisms. The objective of this study was to determine the spectrum and potency of ceftaroline against recent (2010) leading pathogens causing complicated skin and soft-tissue infections (cSSTIs) isolated in Europe. A total of 2438 isolates from the Assessing Worldwide Antimicrobial Resistance and Evaluation (AWARE) programme were identified as cSSTI pathogens. Isolates were collected from patients in 52 medical centres in 19 European countries. Reference susceptibility testing for ceftaroline and commonly used antimicrobials was performed by broth microdilution methodologies. Ceftaroline was very active overall against S. aureus (MIC50/90=0.25/1mg/L) and inhibited 100.0% of isolates at a MIC of ≤2mg/L. Activity against MRSA was documented (MIC50/90=1/2mg/L) but was lower than that observed against MSSA (MIC50/90=0.25/0.25mg/L). Ceftaroline was also very active against 460 β-haemolytic streptococci and 93 VGS (MIC90=0.015mg/L and 0.06mg/L, respectively). Ceftaroline was active against Escherichia coli (MIC50=0.12mg/L) and Klebsiella pneumoniae (MIC50=0.06mg/L) not expressing extended-spectrum β-lactamases, with activity similar to ceftriaxone and ceftazidime. In summary, this study documents the potent in vitro activity of ceftaroline when tested against recent pathogens isolated from patients with cSSTI in Europe.

1529 The Study of the Effect of Cumin Seeds Extracts on some Pathogenic Bacterial Agents

Background and AimsThe antimicrobial effects of cumin (Cuminum cyminum L.), as an agent, have been mentioned previously. In this study the inhibitory effect of alcoholic and aqueous extracts on some...

Antimicrobial susceptibility of bacterial pathogens associated with community-acquired respiratory tract infections in Asia: report from the Community-Acquired Respiratory Tract Infection Pathogen Surveillance (CARTIPS) study, 2009–2010

A multicentre resistance surveillance study [Community-Acquired Respiratory Tract Infection Pathogen Surveillance (CARTIPS)] investigating the susceptibilities of 2963 clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, meticillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus spp. from Asia against 12 antimicrobial agents was undertaken from 2009 to 2010. Based on the breakpoints for oral penicillin V recommended by the Clinical and Laboratory Standards Institute, the prevalence of penicillin-non-susceptible S. pneumoniae (PNSSP) ranged from 46% to 100%. Azithromycin and clarithromycin exhibited variable resistance rates of 0–88% against S. pneumoniae, 0–57% against MSSA and 0–76.5% against Streptococcus spp. isolates. The prevalence of extended-spectrum β-lactamase-producing K. pneumoniae varied from 5.1% to 58.5%. β-Lactamase production rates amongst H. influenzae isolates ranged from 15% to 46.6% and amongst M. catarrhalis isolates from 90% to 100%. Amongst M. catarrhalis isolates, macrolide resistance and cefaclor resistance rates of 5.8% and 1.2%, respectively, were found, mainly in Mainland China. Levofloxacin resistance rates of 0–3.9% with a MIC90 (minimum inhibitory concentration causing inhibition of 90% of isolates) of 1–2mg/L and moxifloxacin resistance rates of 0–1.7% with a MIC90 of 0.125–0.5mg/L were found amongst PNSSP isolates. Moxifloxacin was very active against Streptococcus spp., H. influenzae and M. catarrhalis isolates, with MIC90 values of 0.125–0.25, 0.032–0.5 and 0.064–0.125mg/L, respectively. These results from the CARTIPS study have confirmed some significant regional differences in the antimicrobial susceptibilities of S. pneumoniae, MSSA, K. pneumoniae, H. influenzae and Streptococcus spp. and emphasise the importance of antimicrobial surveillance programmes for guiding empirical therapy and for focusing interventional control of antimicrobial resistance in distinct geographic areas.

Evaluation of the activity of fusidic acid tested against contemporary Gram-positive clinical isolates from the USA and Canada

We evaluated the antimicrobial activity of fusidic acid (CEM-102) against 1140 clinical strains of Gram-positive bacteria obtained from patients with bacteraemia or skin and skin-structure infections collected in more than 30 medical centres in the USA and Canada over a 10-year period (1997–2006). Fusidic acid was very active against meticillin-susceptible Staphylococcus aureus (MSSA), meticillin-resistant S. aureus (MRSA) and coagulase-negative staphylococci (CoNS), with MIC 90 values (minimum inhibitory concentration encompassing 90% of isolates tested) at 0.12 μg/mL for US strains of MSSA, MRSA and CoNS and 0.25 μg/mL for Canadian strains of MSSA and MRSA. A progressive increase in fusidic acid resistance was observed among Canadian strains of S. aureus (12.2% in 2005–2006) and among Canadian strains of CoNS. In contrast, no fusidic acid resistance was detected among US S. aureus strains and only 1.5% among CoNS. Fusidic acid was equally active against community-acquired MRSA and linezolid-resistant staphylococci. Fusidic acid exhibited equal or greater potency against staphylococci compared with vancomycin, daptomycin and linezolid.

Inoculum Effect with Cefazolin among Clinical Isolates of Methicillin-Susceptible Staphylococcus aureus : Frequency and Possible Cause of Cefazolin Treatment Failure

Methicillin (meticillin)-susceptible Staphylococcus aureus (MSSA) strains producing large amounts of type A beta-lactamase (Bla) have been associated with cefazolin failures, but the frequency and impact of these strains have not been well studied. Here we examined 98 MSSA clinical isolates and found that 26% produced type A Bla, 15% type B, 46% type C, and none type D and that 13% lacked blaZ. The cefazolin MIC(90) was 2 microg/ml for a standard inoculum and 32 microg/ml for a high inoculum, with 19% of isolates displaying a pronounced inoculum effect (MICs of >or=16 microg/ml with 10(7) CFU/ml) (9 type A and 10 type C Bla producers). At the high inoculum, type A producers displayed higher cefazolin MICs than type B or C producers, while type B and C producers displayed higher cefamandole MICs. Among isolates from hemodialysis patients with MSSA bacteremia, three from the six patients who experienced cefazolin failure showed a cefazolin inoculum effect, while none from the six patients successfully treated with cefazolin showed an inoculum effect, suggesting an association between these strains and cefazolin failure (P = 0.09 by Fisher's exact test). In summary, 19% of MSSA clinical isolates showed a pronounced inoculum effect with cefazolin, a phenomenon that could explain the cases of cefazolin failure previously reported for hemodialysis patients with MSSA bacteremia. These results suggest that for serious MSSA infections, the presence of a significant inoculum effect with cefazolin could be associated with clinical failure in patients treated with this cephalosporin, particularly when it is used at low doses.

Modification in prescribing practices for third-generation cephalosporins and ciprofloxacin is associated with a reduction in meticillin-resistant Staphylococcus aureus bacteraemia rate

To decrease the incidence of hospital infections caused by meticillin-resistant Staphylococcus aureus (MRSA), an educational intervention study was performed in which the use of intravenous ciprofloxacin and third-generation cephalosporins was discouraged. The effect was assessed by observing the MRSA bacteraemia rate both within the hospital and the intensive care unit for 18 months before, and 16 months after, the two-month intervention programme. MRSA bacteraemia rate throughout the hospital was reduced by 62.9% (P<0.001) by the end of the study and MRSA colonisation rate was reduced by 38.4% (not significant). There was no concomitant decrease in episodes of bacteraemia caused by meticillin-susceptible Staphylococcus aureus (MSSA) during the study period. There was a fall in hospital dispensing of both ciprofloxacin (80.4%) and third-generation cephalosporins (75.2%). The overall incidence of MRSA bloodstream infections within critical care was reduced (4.200 vs 0.272 per 1000 occupied bed-days) but this was not significant.

Long-term outcomes following infection with meticillin-resistant or meticillin-susceptible Staphylococcus aureus

Staphylococcus aureus (SA) is becoming increasingly resistant to antibiotics in hospitals and the community. Long-term outcomes following susceptible and resistant SA infection have not been studied. We performed a retrospective matched pair analysis of all patients with positive culture for meticillin-resistant SA (MRSA) or meticillin-susceptible SA (MSSA) from any site to assess the outcomes of infection. Data were collected for length of hospitalisation and in-hospital mortality, as well as longer-term outcomes including all-cause mortality, number of rehospitalisations and subsequent cultures for SA during the year following infection. Twelve months after their initial SA infection, 42% of patients were dead. There were no differences between the groups in short-term mortality, length of hospitalisation, number of subsequent hospitalisations and cultures for SA during the year following infection. Following discharge, however, MRSA infection was associated with higher mortality than MSSA at three months (32% vs 18% P=0.02), six months (42% vs 22% P=0.002) and 12 months (51% vs 32% P=0.005). In conclusion, SA infection is associated with a high one-year all-cause mortality. Most deaths occur after discharge. The likelihood of dying during the year following infection is higher for patients with MRSA infection than for those with MSSA infection.