Changing characteristics of S. aureus bacteremia caused by PVL-negative, MRSA strain over 11 years.

Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important cause of infection. We conducted a longitudinal study to evaluate changes in clinical and microbiological characteristics as well as outcomes of sequence type (ST) 72 MRSA bacteremia. We reviewed adult patients enrolled in a prospective cohort with ST72 MRSA bacteremia from August 2008 to December 2018 at Asan Medical Center, Seoul, South Korea. Changes in clinical characteristics, outcomes, and microbiological characteristics of patients over time were evaluated. Generalized linear and linear regression models were used to evaluate changes. Of the 1,760 isolates, 915 (62%) were MRSA bacteremia and 292 (31.9%) were ST72 MRSA. During the study period, the relative risk (RR) of MRSA bacteremia decreased annually by 3.7%; however, among MRSA bacteremia, RR of ST72 MRSA increased annually by 8.5%. Vancomycin minimum inhibitory concentration (MIC) decreased over the study period. Metastatic infection, persistent bacteremia, and recurrence of bacteremia within 12 weeks decreased significantly. There were no significant changes in 30-d and 12-week mortality. Antibiotic susceptibility of ST72 MRSA was evaluated, and the resistance rate to erythromycin decreased significantly. ST72 MRSA incidence increased annually; its vancomycin MIC and erythromycin resistance rate decreased over the 11 years.

Genetic and phenotypic diversity of methicillin-resistant Staphylococcus aureus among Japanese inpatients in the early 1980s.

To trace the linkage between Japanese healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) strains in the early 1980s and the 2000s onward, we performed molecular characterizations using mainly whole-genome sequencing. Among the 194 S. aureus strains isolated, 20 mecA-positive MRSA (10.3%), 8 mecA-negative MRSA (4.1%) and 3 mecA-positive methicillin-susceptible S. aureus (MSSA) (1.5%) strains were identified. The most frequent sequence type (ST) was ST30 (n = 11), followed by ST5 (n = 8), ST81 (n = 4), and ST247 (n = 3). Rates of staphylococcal cassette chromosome mec (SCCmec) types I, II, and IV composed 65.2%, 13.0%, and 17.4% of isolates, respectively. Notably, 73.3% of SCCmec type I strains were susceptible to imipenem unlike SCCmec type II strains (0%). ST30-SCCmec I (n = 7) and ST5-SCCmec I (n = 5) predominated, whereas only two strains exhibited imipenem-resistance and were tst-positive ST5-SCCmec II, which is the current Japanese HA-MRSA genotype. All ST30 strains shared the common ancestor strain 55/2053, which caused the global pandemic of Panton-Valentine leukocidin-positive MSSA in Europe and the United States in the 1950s. Conspicuously more heterogeneous, the population of HA-MRSA clones observed in the 1980s, including the ST30-SCCmec I clone, has shifted to the current homogeneous population of imipenem-resistant ST5-SCCmec II clones, probably due to the introduction of new antimicrobials.

Methicillin-resistant Staphylococcus aureus bacteraemia, 2003-2015: Comparative evaluation of changing trends in molecular epidemiology and clinical outcomes of infections.

Methicillin-resistant Staphylococcus aureus (MRSA) is a prominent pathogen causing invasive infections such as bacteraemia. The continued excessive use of antibiotics to treat MRSA infections has resulted in the evolution of antimicrobial resistant of S. aureus. This study aims to perform a comparative evaluation of changing trends in molecular epidemiology of MRSA and clinical characteristics of patients. This study shows that ST22-MRSA-IV has gradually replaced ST239-MRSA-III as the predominant MRSA clone in the tertiary teaching hospital studied. Independent predictors of mortality among patients included devices in situ at the time of infection, pre-exposure to macrolides, catheter-related bloodstream infection and mono-microbial infection. Hence, our study affirmed community-associated MRSA, which was previously identified from individuals without any exposure to healthcare settings, has now emerged in healthcare settings, causing healthcare-associated MRSA infections.

The 'H-Bug' epidemic: lessons from antibiotic-resistant staphylococcal outbreaks in New Zealand hospitals from 1955-1963.

Deadly outbreaks of antibiotic-resistant staphylococcal infection occurred in New Zealand from the mid-1950s to early 1960s. The 'H' or 'Hospital-Bug' epidemic was part of a pandemic wave characterised by high numbers of nosocomial staphylococcal infections and the capacity of Staphylococcus aureus to develop resistance to commonly used antibiotics. Surgical patients and childbearing women and babies proved particularly vulnerable to the predominant pathogenic strain, identified as phage type 80/81. The post-war baby boom was at its height in New Zealand, and overcrowded maternity hospitals and outdated nursing techniques increased the risks of infection. The outbreaks challenged the medical profession, which had become reliant on antibiotics for prophylaxis and treatment. The Health Department ascribed responsibility for the indiscriminate use of antibiotics to medical practitioners but had little control over their prescribing habits. Confronted by increasing infection rates and falling public confidence in the maternity services, health officials supported a fundamental change in maternity care to 'rooming-in' of mother and baby, epidemiological research on staphylococcal transmission in hospitals, notification of nosocomial infections, improved barrier nursing and heightened awareness of appropriate aseptic techniques. Phage type 80/81 waned in the early 1960s concurrent with the arrival of methicillin but the emergence of methicillin-resistant S. aureus (MRSA) in the 1980s, vancomycin-resistant S. aureus (VRSA) in the 2000s, and the rapid emergence and spread of multi-drug resistant Gram-negative bacteria over the past decade, highlights the potential for further outbreaks while the use of antimicrobials remains high. Non-pharmacological interventions such as those promoted during the 'H-Bug' epidemic are likely to be central to controlling future waves of resistant nosocomial infection.

Age-Dependent Increase in Incidence of Staphylococcus aureus Bacteremia, Denmark, 2008-2015.

Staphylococcus aureus bacteremia (SAB) is a major cause of illness and death worldwide. We analyzed temporal trends of SAB incidence and death in Denmark during 2008-2015. SAB incidence increased 48%, from 20.76 to 30.37 per 100,000 person-years, during this period (p<0.001). The largest change in incidence was observed for persons >80 years of age: a 90% increase in the SAB rate (p<0.001). After adjusting for demographic changes, annual rates increased 4.0% (95% CI 3.0-5.0) for persons <80 years of age, 8.4% (95% CI 7.0-11.0) for persons 80-89 years of age, and 13.0% (95% CI 9.0-17.5) for persons >90 years of age. The 30-day case-fatality rate remained stable at 24%; crude population death rates increased by 53% during 2008-2015 (p<0.001). Specific causes and mechanisms for this rapid increase in SAB incidence among the elderly population remain to be clarified.

Staphylococcus aureus Bacteremia in Children of Rural Areas of The Gambia, 2008-2015.

Staphylococcus aureus bacteremia is a substantial cause of childhood disease and death, but few studies have described its epidemiology in developing countries. Using a population-based surveillance system for pneumonia, sepsis, and meningitis, we estimated S. aureus bacteremia incidence and the case-fatality ratio in children <5 years of age in 2 regions in the eastern part of The Gambia during 2008-2015. Among 33,060 children with suspected pneumonia, sepsis, or meningitis, we performed blood culture for 27,851; of 1,130 patients with bacteremia, 198 (17.5%) were positive for S. aureus. S. aureus bacteremia incidence was 78 (95% CI 67-91) cases/100,000 person-years in children <5 years of age and 2,080 (95% CI 1,621-2,627) cases/100,000 person-years in neonates. Incidence did not change after introduction of the pneumococcal conjugate vaccine. The case-fatality ratio was 14.1% (95% CI 9.6%-19.8%). Interventions are needed to reduce the S. aureus bacteremia burden in The Gambia, particularly among neonates.

USA300 methicillin-resistant Staphylococcus aureus in Stockholm, Sweden, from 2008 to 2016.

Methicillin-resistant Staphylococcus aureus (MRSA) USA300 isolates have been recognized globally, not only in community but also in healthcare settings. USA300 isolates were initially resistant only to methicillin, but resistance to non-ß-lactams has emerged with time. To evaluate the prevalence and antimicrobial susceptibility of USA300 isolates in Stockholm, we conducted a nine-year retrospective study. Of 5359 consecutive MRSA cases in Stockholm, isolates from 285 cases were USA300 strains according to the pulsed-field gel electrophoresis pattern. Of these cases, repeated isolates with altered antibiotic resistance patterns were observed in six individuals. Therefore, antimicrobial susceptibility testing was performed on totally 291 isolates. To study the phylogenetic relatedness of isolates in transmission events and genomic resistance traits, 35 isolates were further studied by whole genome sequencing (WGS). The incidence of MRSA was increased from 17.6 per 100,000 inhabitants in 2008 to 37.3 per 100,000 inhabitants in 2016, while the proportion of USA300 cases declined from 6.6% in 2008 to 2.6% in 2016. Among the USA300 isolates, 73.5% were community-associated, 21.3% healthcare-associated, and 5.2% had unknown acquisition. The highest resistance rate among non-ß-lactams was found in erythromycin (86%), followed by fluoroquinolones (68-69%). 57% of the isolates were resistant to both erythromycin and fluoroquinolone. Simultaneous resistance to four non-ß-lactam antibiotic classes was found in six isolates. Four isolates were susceptible to all non-ß-lactam antibiotics. Ceftaroline, daptomycin, linezolid, mupirocin, rifampicin, teicoplanin, telavancin, trimethoprim-sulfamethoxazole and vancomycin retained full activity in the study. WGS analysis indicated that isolates from an outbreak were phylogenetically closely related. In conclusion, USA300 MRSA isolates in Stockholm have neither been limited to the community setting, nor remained susceptible to non-ß-lactam agents. WGS is becoming a useful tool in tracing transmission events. The results herein provide the most up-to-date and comprehensive information regarding status of USA300 strains in this geographic area.

Increased Community-Associated Infections Caused by Panton-Valentine Leukocidin-Negative MRSA, Shanghai, 2005-2014.

During 2005-2014, community-associated methicillin-resistant Staphylococcus aureus infections increased in Shanghai, China. Most infections were caused by sequence type 59 S. aureus that lacked Panton-Valentine leukocidin. This finding challenges the notion that Panton-Valentine leukocidin is necessary for epidemiologic success of community-associated methicillin-resistant S. aureus.

Australian Group on Antimicrobial Resistance Australian Staphylococcus aureus Sepsis Outcome Programme annual report, 2014.

From 1 January to 31 December 2014, 27 institutions around Australia participated in the Australian Staphylococcal Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2014 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to methicillin and to characterise the molecular epidemiology of the isolates. Overall, 18.8% of the 2,206 SAB episodes were methicillin resistant, which was significantly higher than that reported in most European countries. The 30-day all-cause mortality associated with methicillin-resistant SAB was 23.4%, which was significantly higher than the 14.4% mortality associated with methicillin-sensitive SAB (P <0.0001). With the exception of the beta-lactams and erythromycin, antimicrobial resistance in methicillin-sensitive S. aureus remains rare. However in addition to the beta-lactams, approximately 50‰ of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin and ciprofloxacin and approximately 15% were resistant to co-trimoxazole, tetracycline and gentamicin. When applying the European Committee on Antimicrobial Susceptibility Testing breakpoints, teicoplanin resistance was detected in 2 S. aureus isolates. Resistance was not detected for vancomycin or linezolid. Resistance to non-beta-lactam antimicrobials was largely attributable to 2 healthcare-associated MRSA clones; ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). ST22-IV [2B] (EMRSA-15) has become the predominant healthcare associated clone in Australia. Sixty per cent of methicillin-resistant SAB were due to community-associated (CA) clones. Although polyclonal, almost 44% of community-associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA) and ST1-IV [2B] (WA1). CA-MRSA, in particular the ST45-V [5C2&5] (WA84) clone, has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. As CA-MRSA is well established in the Australian community it is important that antimicrobial resistance patterns in community and healthcare-associated SAB is monitored as this information will guide therapeutic practices in treating S. aureus sepsis.

Community-onset Staphylococcus aureus Surveillance Programme annual report, 2012.

In 2012, the Australian Group on Antimicrobial Resistance (AGAR) conducted a community-onset period-prevalence survey of clinical Staphylococcus aureus isolated from hospital outpatients and general practice patients including nursing homes, long term care facilities and hospice patients. Day surgery and dialysis patients were excluded. Twenty-nine medical microbiology laboratories from all state and mainland territories participated. Isolates were tested by Vitek2® (AST-P612 card). Results were compared with previous AGAR community surveys. Nationally, the proportion of S. aureus that were methicillin-resistant S. aureus (MRSA) increased significantly from 11.5% in 2000 to 17.9% in 2012 (P<0.0001). Resistance to the non-ß-lactam antimicrobials varied between regions. No resistance was detected to vancomycin, teicoplanin or linezolid. Resistance in methicillin susceptible S. aureus was rare apart from erythromycin (12.8%) and was absent for vancomycin, teicoplanin, linezolid and daptomycin. The proportion of S. aureus characterised as health care-associated MRSA (HA-MRSA) was 5.1%. Three HA-MRSA clones were characterised, with 72.9% and 26.4% of HA-MRSA classified as ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA) respectively. Multi-clonal community-associated MRSA (CA-MRSA) accounted for 12.5% of all S. aureus. Regional variation in resistance in MRSA was primarily due to the differential distribution of the 2 major HA-MRSA clones; ST239-III [3A] (Aus-2/3 EMRSA), which is resistant to multiple non-ß-lactam antimicrobials, and ST22-IV [2B] (EMRSA-15), which is resistant to ciprofloxacin and typically erythromycin. Although the majority of CA-MRSA were non-multi-resistant, a significant expansion of Panton-Valentine leukocidin (PVL) positive CA-MRSA clones has occurred nationally. The mean age of patients (31.7 years, 95% CI 28.9-34.5) with a PVL positive CA-MRSA infection was significantly lower (P<0.0001), than the mean age of patients with a PVL negative CA-MRSA infection (55.7 years, 95% CI 50.7-60.6). This shift in the molecular epidemiology of MRSA clones in the Australian community will potentially increase the number of young Australians with skin and soft tissue infections requiring hospitalisation.

Staphylococcus aureus bacteremia at 5 US academic medical centers, 2008-2011: significant geographic variation in community-onset infections.

BACKGROUND: The incidence of community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) bacteremia rose from the late 1990s through the 2000s. However, hospital-onset (HO) MRSA rates have recently declined in the United States and Europe. METHODS: Data were abstracted from infection prevention databases between 1 January 2008 and 31 December 2011 at 5 US academic medical centers to determine the number of single-patient blood cultures positive for MRSA and methicillin-susceptible S. aureus (MSSA) per calendar year, stratified into CO and HO infections. RESULTS: Across the 5 centers, 4171 episodes of bacteremia were identified. Center A (Los Angeles, California) experienced a significant decline in CO-MRSA bacteremia rates (from a peak in 2009 of 0.42 to 0.18 per 1000 patient-days in 2011 [P = .005]), whereas CO-MSSA rates remained stable. Centers B (San Francisco, California), D (Chicago, Illinois), and E (Raleigh-Durham, North Carolina) experienced a stable incidence of CO-MRSA and CO-MSSA bacteremia. In contrast, at center C (New York, New York), the incidence of CO-MRSA increased >3-fold (from 0.11 to 0.34 cases per 1000 patient-days [P < .001]). At most of the sites, HO-MRSA decreased and HO-MSSA rates were stable. USA300 accounted for 52% (104/202) of genotyped MRSA isolates overall, but this varied by center, ranging from 35% to 80%. CONCLUSIONS: CO-MRSA rates and the contribution of USA300 MRSA varied dramatically across diverse geographical areas in the United States. Enhanced infection control efforts are unlikely to account for such variation in CO infection rates. Bioecological and clinical explanations for geographical differences in CO-MRSA bacteremia rates merit further study.

Molecular epidemiology and antimicrobial resistance of methicillin-resistant Staphylococcus aureus bloodstream isolates in Taiwan, 2010.

The information of molecular characteristics and antimicrobial susceptibility pattern of methicillin-resistant Staphylococcus aureus (MRSA) is essential for control and treatment of diseases caused by this medically important pathogen. A total of 577 clinical MRSA bloodstream isolates from six major hospitals in Taiwan were determined for molecular types, carriage of Panton-Valentine leukocidin (PVL) and sasX genes and susceptibilities to 9 non-beta-lactam antimicrobial agents. A total of 17 genotypes were identified in 577 strains by pulsotyping. Five major pulsotypes, which included type A (26.2%, belonging to sequence type (ST) 239, carrying type III staphylococcal chromosomal cassette mec (SCCmec), type F (18.9%, ST5-SCCmecII), type C (18.5%, ST59-SCCmecIV), type B (12.0%, ST239-SCCmecIII) and type D (10.9%, ST59-SCCmecVT/IV), prevailed in each of the six sampled hospitals. PVL and sasX genes were respectively carried by ST59-type D strains and ST239 strains with high frequencies (93.7% and 99.1%, respectively) but rarely detected in strains of other genotypes. Isolates of different genotypes and from different hospitals exhibited distinct antibiograms. Multi-resistance to ≥3 non-beta-lactams was more common in ST239 isolates (100%) than in ST5 isolates (97.2%, P = 0.0347) and ST59 isolates (8.2%, P<0.0001). Multivariate analysis further indicated that the genotype, but not the hospital, was an independent factor associated with muti-resistance of the MRSA strains. In conclusion, five common MRSA clones with distinct antibiograms prevailed in the major hospitals in Taiwan in 2010. The antimicrobial susceptibility pattern of invasive MRSA was mainly determined by the clonal distribution.

X-Ray treatment of carbuncles and furuncles (boils): a historical assessment.

The goal of this article was to assess the historical role of radiotherapy in the treatment of selected inflammatory diseases. The specific research involved a literature-based assessment of the use of x-rays during the first half of the 20th century for the treatment of furuncles and carbuncles, the potentially serious staphylococcus infections. X-Rays were reported to be effective as a treatment at relatively low dose, about 10-20% of the skin erythema dose, which often quickly and profoundly reduce pain and accelerate the resolution/healing of the furuncles and carbuncles. These findings were based on considerable clinical experience that was generally reported in the form of case studies. The mechanism of x-ray-induced reduction of inflammation and acceleration of healing was suggested to result from a combination of immune alterations that enhanced phagocytosis as well as via an anti-localization effect on the pathogenic organism that facilitates their destruction.

The challenge of antibiotic-resistant Staphylococcus: lessons from hospital nurseries in the mid-20th century.

In the late 1940s, epidemics of antibiotic-resistant strains of Staphylococcus aureus began to plague postpartum nurseries in hospitals across the United States. Exacerbated by overcrowding and nursing shortages, resistant S. aureus outbreaks posed a novel challenge to physicians and nurses heavily reliant on antibiotics as both prophylaxis and treatment. This paper explores the investigation of the reservoir, mode of transmission, and virulence of S. aureus during major hospital outbreaks and the subsequent implementation of novel infection control measures from the late 1940s through the early 1960s. The exploration of these measures reveals a shift in infection control policy as hospitals, faced with the failure of antibiotics to slow S. aureus outbreaks, implemented laboratory culture routines, modified nursery structure and layout, and altered nursing staff procedures to counter various forms of S. aureus transmission. Showcasing the need for widespread epidemiologic surveillance, ultimately manifesting itself in specialized "hospital epidemiology" training promoted in the 1970s, the challenges faced by hospital nurses in the 1950s prove highly relevant to the continued struggle with methicillin-resistant Staphylococcus aureus (MRSA) and other resistant nosocomial infections.

Changing epidemiology of methicillin-resistant Staphylococcus aureus in Canada.

OBJECTIVES: To compare the demographics, antimicrobial susceptibilities and molecular epidemiology of community-associated (CA) and healthcare-associated (HA) methicillin-resistant Staphylococcus aureus (MRSA) in Canada. METHODS: Between 2007 and 2011, 1266 MRSA were collected from inpatients and outpatients attending tertiary-care medical centres across Canada. Susceptibility testing was performed using broth microdilution and isolates were characterized by spa typing and PCR to detect the Panton-Valentine leucocidin (PVL) gene. Detection of heterogeneous vancomycin-intermediate S. aureus (hVISA) was performed using the Etest macromethod and confirmed by population analysis profiling. RESULTS: The annual proportion of S. aureus that were methicillin resistant decreased from 26.1% in 2007 to 19.3% in 2011 (P= 0.0002). Of 1266 MRSA isolated, 366 (28.9%) were CA-MRSA genotypes and 868 (68.6%) were HA-MRSA genotypes. The proportion of MRSA represented by CA-MRSA genotypes increased from 19.7% to 36.4% between 2007 and 2011 (P < 0.0001). CMRSA10 (USA300) was the predominant CA-MRSA genotype (22.1%); the most common HA-MRSA genotype was CMRSA2 (USA100/800) (58.1%). PVL was detected in 328/366 (89.6%) of CA-MRSA genotypes and 6/868 (0.7%) of HA-MRSA genotypes. The hVISA phenotype was detected in 7/27 (25.9%) of MRSA with a vancomycin MIC of 2 mg/L. CONCLUSIONS: The most frequent CA-MRSA genotype was CMRSA10 (USA300), while CMRSA2 (USA100/800) was the predominant HA-MRSA genotype. Despite a decrease in the numbers of MRSA, the proportion of CMRSA10 (USA300) CA-MRSA has risen significantly between 2007 and 2011 in Canada.