Burdens of Invasive Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus Disease, Minnesota, USA.

During August 1, 2014-July 31, 2015, in 2 counties in Minnesota, USA, incidence of invasive methicillin-susceptible Staphylococcus aureus (MSSA) (27.1 cases/100,000 persons) was twice that of invasive methicillin-resistant S. aureus (13.1 cases/100,000 persons). MSSA isolates were more genetically diverse and susceptible to more antimicrobial drugs than methicillin-resistant S. aureus isolates.

Randomized controlled trial of a self-administered five-day antiseptic bundle versus usual disinfectant soap showers for preoperative eradication of Staphylococcus aureus colonization.

OBJECTIVE: To determine the efficacy in eradicating Staphylococcus aureus (SA) carriage of a 5-day preoperative decolonization bundle compared to 2 disinfectant soap showers, with both regimens self-administered at home. DESIGN: Open label, single-center, randomized clinical trial. SETTING: Ambulatory orthopedic, urologic, neurologic, colorectal, cardiovascular, and general surgery clinics at a tertiary-care referral center in the United States.ParticipantsPatients at the University of Minnesota Medical Center planning to have elective surgery and not on antibiotics. METHODS: Consenting participants were screened for SA colonization using nasal, throat, axillary, and perianal swab cultures. Carriers of SA were randomized, stratified by methicillin resistance status, to a decolonization bundle group (5 days of nasal mupirocin, chlorhexidine gluconate [CHG] bathing, and CHG mouthwash) or control group (2 preoperative showers with antiseptic soap). Colonization status was reassessed preoperatively. The primary endpoint was absence of SA at all 4 screened body sites. RESULTS: Of 427 participants screened between August 31, 2011, and August 9, 2016, 127 participants (29.7%) were SA carriers. Of these, 121 were randomized and 110 were eligible for efficacy analysis (57 decolonization bundle group, 53 control group). Overall, 90% of evaluable participants had methicillin-susceptible SA strains. Eradication of SA at all body sites was achieved for 41 of 57 participants (71.9%) in the decolonization bundle group and for 13 of 53 participants (24.5%) in the control group, a difference of 47.4% (95% confidence interval [CI], 29.1%-65.7%; P<.0001). CONCLUSION: An outpatient preoperative antiseptic decolonization bundle aimed at 4 body sites was significantly more effective in eradicating SA than the usual disinfectant showers (ie, the control).Trial RegistrationClinicalTrials.gov identifier: NCT02182115.

Accuracy and reproducibility of the Etest to detect drug-resistant Neisseria gonorrhoeae to contemporary treatment.

PURPOSE: Neisseria gonorrhoeae is a sexually transmitted bacterial pathogen that continues to evolve to become resistant to known antibiotics. In preparing for potential emergence, the Centers for Disease Control and Prevention recommends that clinical laboratories maintain or develop protocols to assess antibiotic susceptibly for this organism. This study examines the intra-laboratory variability of using the Etest method to provide consistent MIC values for N. gonorrhoeae and also compared the results of the Etest to known agar dilution MIC values. METHODOLOGY: Clinical N. gonorrhoeae isolates, 100 paired duplicates, were tested by eight laboratories for antibiotic susceptibility to ceftriaxone, cefixime and azithromycin using Etest strips.Results/Key findings. Overall, >80 % of the paired Etest MIC values were within one log2 dilution of the replicate. When compared to the agar dilution reference method, the cefixime Etest MIC values were consistently underreported by one dilution (seven laboratories) or two dilutions (one laboratory). The azithromycin Etest MIC values agreed 90.7 % with the agar dilution MIC values while the agreement with ceftriaxone was 90.9 %. CONCLUSION: Overall, the Etest method yielded reproducible MIC values within each laboratory with the azithromycin and ceftriaxone MIC results consistent to the reference agar dilution method while the cefixime result tended to provide a lower MIC value.

vanG element insertions within a conserved chromosomal site conferring vancomycin resistance to Streptococcus agalactiae and Streptococcus anginosus.

Three vancomycin-resistant streptococcal strains carrying vanG elements (two invasive Streptococcus agalactiae isolates [GBS-NY and GBS-NM, both serotype II and multilocus sequence type 22] and one Streptococcus anginosus [Sa]) were examined. The 45,585-bp elements found within Sa and GBS-NY were nearly identical (together designated vanG-1) and shared near-identity over an ~15-kb overlap with a previously described vanG element from Enterococcus faecalis. Unexpectedly, vanG-1 shared much less homology with the 49,321-bp vanG-2 element from GBS-NM, with widely different levels (50% to 99%) of sequence identity shared among 44 related open reading frames. Immediately adjacent to both vanG-1 and vanG-2 were 44,670-bp and 44,680-bp integrative conjugative element (ICE)-like sequences, designated ICE-r, that were nearly identical in the two group B streptococcal (GBS) strains. The dual vanG and ICE-r elements from both GBS strains were inserted at the same position, between bases 1328 and 1329, within the identical RNA methyltransferase (rumA) genes. A GenBank search revealed that although most GBS strains contained insertions within this specific site, only sequence type 22 (ST22) GBS strains contained highly related ICE-r derivatives. The vanG-1 element in Sa was also inserted within this position corresponding to its rumA homolog adjacent to an ICE-r derivative. vanG-1 insertions were previously reported within the same relative position in the E. faecalis rumA homolog. An ICE-r sequence perfectly conserved with respect to its counterpart in GBS-NY was apparent within the same site of the rumA homolog of a Streptococcus dysgalactiae subsp. equisimilis strain. Additionally, homologous vanG-like elements within the conserved rumA target site were evident in Roseburia intestinalis. Importance: These three streptococcal strains represent the first known vancomycin-resistant strains of their species. The collective observations made from these strains reveal a specific hot spot for insertional elements that is conserved between streptococci and different Gram-positive species. The two GBS strains potentially represent a GBS lineage that is predisposed to insertion of vanG elements.

Prevention of antibiotic-nonsusceptible Streptococcus pneumoniae with conjugate vaccines.

BACKGROUND: Streptococcus pneumoniae (pneumococcus) caused approximately 44000 US invasive pneumococcal disease (IPD) cases in 2008. Antibiotic nonsusceptibility complicates IPD treatment. Using penicillin susceptibility breakpoints adopted in 2008, we evaluated antibiotic-nonsusceptible IPD trends in light of the introductions of a 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 and a 13-valent pneumococcal conjugate vaccine (PCV13) in 2010. METHODS: IPD cases were defined by isolation of pneumococcus from a normally sterile site in individuals residing in Active Bacterial Core surveillance (ABCs) areas during 1998-2008. Pneumococci were serotyped and tested for antibiotic susceptibility using broth microdilution. RESULTS: During 1998-2008, ABCs identified 43198 IPD cases. Penicillin-nonsusceptible strains caused 6%-14% of IPD cases, depending on age. Between 1998-1999 and 2008, penicillin-nonsusceptible IPD rates declined 64% for children aged <5 years (12.1-4.4 cases per 100000), and 45% for adults aged ≥65 (4.8-2.6 cases per 100000). Rates of IPD nonsusceptible to multiple antibiotics mirrored these trends. During 2007-2008, serotypes in PCV13 but not PCV7 caused 78%-97% of penicillin-nonsusceptible IPD, depending on age. CONCLUSIONS: Antibiotic-nonsusceptible IPD rates remain below pre-PCV7 rates for children <5 and adults ≥65 years old. PCV13 vaccines hold promise for further nonsusceptibility reductions.

Evaluation of disk approximation and single-well broth tests for detection of inducible clindamycin resistance in Streptococcus pneumoniae.

This study evaluated an agar disk diffusion D-zone test and an erythromycin-clindamycin (ERY + CLI) single-well broth test for inducible CLI resistance in Streptococcus pneumoniae. The standard CLSI disk approximation test and a single-well combination test incorporating 1 plus 0.5 µg/ml ERY + CLI detected >96% of isolates containing the ermB determinant.

Collaborative evaluation of an erythromycin-clindamycin combination well for detection of inducible clindamycin resistance in beta-hemolytic streptococci by use of the CLSI broth microdilution method.

Constitutive or inducible clindamycin resistance can occur in beta-hemolytic streptococci due to the presence of an erm gene. The Clinical and Laboratory Standards Institute (CLSI) has recommended a disk approximation test (D-zone test) with erythromycin and clindamycin disks and a single-well broth test combining erythromycin and clindamycin for detection of inducible clindamycin resistance in staphylococci, but only a disk approximation test for the beta-hemolytic streptococci. This collaborative study assessed two different erythromycin and clindamycin concentration combinations in single wells (1 µg/ml + 0.25 µg/ml [erythromycin plus clindamycin] and 1 µg/ml + 0.5 µg/ml) with three different brands of Mueller-Hinton broth supplemented with 3% lysed horse blood for testing of frozen panels prepared for this study. All labs performed the D-zone test as described by the CLSI. A total of 155 nonduplicate streptococcal isolates (50 group A, 48 group B, 28 group C, and 29 group G isolates) were tested; 99 isolates showed inducible resistance by the D-zone test. There were some differences noted based upon the test medium. The sensitivity of the erythromycin plus clindamycin combination of 1 µg/ml + 0.25 µg/ml was 91 to 100%, while the sensitivity of the combination of 1 µg/ml + 0.5 µg/ml was 95 to 100%. Specificity overall was 98%. The slightly higher sensitivity of the combination of 1 µg/ml + 0.5 µg/ml is recommended. This study has demonstrated that a single-well microdilution test incorporating erythromycin and clindamycin in combination is a sensitive and specific indicator of inducible clindamycin resistance and could be included in routine test panels.

Invasive group B streptococcal disease in the elderly, Minnesota, USA, 2003-2007.

In Minnesota, incidence of invasive group B streptococcal disease was 3 times greater in older adults in long-term care facilities than in older adults in community settings (67.7/100,000 vs. 21.4/100,000) during 2003-2007. The overall case-fatality rate was 6.8%, and concurrent conditions were common among both groups.

Community-associated methicillin-resistant Staphylococcus aureus: trends in case and isolate characteristics from six years of prospective surveillance.

OBJECTIVES: In 2000, the Minnesota Department of Health (MDH) implemented active, sentinel site surveillance for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Data from 2000-2005 were analyzed to determine trends in case characteristics, pulsed-field types (PFTs), and antimicrobial susceptibilities including inducible clindamycin resistance (ICR). METHODS: Active sentinel site surveillance was initiated in 2000 at 12 hospital laboratories that served inpatients and outpatients. Patient medical records were reviewed to determine if they met the epidemiologic case criteria for CA-MRSA; isolates were obtained from patients meeting these criteria. The MDH Public Health Laboratory performed pulsed-field gel electrophoresis subtyping and antimicrobial susceptibility testing, including ICR. RESULTS: The proportion of MRSA cases classified as CA increased from 11% to 33% (p<0.01). The proportion of cases with skin or soft tissue infections also increased compared with other infection types from 75% to 87% (p<0.01). During the surveillance period, USA300 replaced USA400 as the dominant PFT. With the change in dominant PFT, the proportion of isolates susceptible to erythromycin (45% to 13%, p<0.01) and ciprofloxacin (80% to 59%, p<0.01) decreased. The proportion of erythromycin-resistant/clindamycin-susceptible isolates with ICR (93% to 14%, p<0.01) decreased. The proportion of susceptible isolates also changed within the USA300 PFT; the proportion of isolates susceptible to erythromycin (33% vs. 3%) and the proportion susceptible to ciprofloxacin (67% to 62%) decreased significantly. CONCLUSION: CA-MRSA increased dramatically from 2000 to 2005. Changes in the predominant PFT have impacted susceptibility profiles of CA-MRSA, including ICR. Continued surveillance is needed to monitor the changing epidemiology of CA-MRSA and to inform clinical decisions.

Emergence of ciprofloxacin-resistant Neisseria meningitidis in North America.

We report on three cases of meningococcal disease caused by ciprofloxacin-resistant Neisseria meningitidis, one in North Dakota and two in Minnesota. The cases were caused by the same serogroup B strain. To assess local carriage of resistant N. meningitidis, we conducted a pharyngeal-carriage survey and isolated the resistant strain from one asymptomatic carrier. Sequencing of the gene encoding subunit A of DNA gyrase (gyrA) revealed a mutation associated with fluoroquinolone resistance and suggests that the resistance was acquired by means of horizontal gene transfer with the commensal N. lactamica. In susceptibility testing of invasive N. meningitidis isolates from the Active Bacterial Core surveillance system between January 2007 and January 2008, an additional ciprofloxacin-resistant isolate was found, in this case from California. Ciprofloxacin-resistant N. meningitidis has emerged in North America.

Plasmid-Borne erm(T) from invasive, macrolide-resistant Streptococcus pyogenes strains.

Twenty-three isolates of group A streptococci (GAS) recovered from population-based invasive GAS surveillance in the United States were erythromycin resistant, inducibly clindamycin resistant, and lacked known macrolide resistance determinants. These 23 isolates, representing four different clones, contained a broad-host-range plasmid carrying the erm(T) methylase gene, which has not been detected in GAS previously.

A community outbreak of conjunctivitis caused by nontypeable Streptococcus pneumoniae in Minnesota.

BACKGROUND: The Minnesota Department of Health (MDH) was notified of an outbreak of conjunctivitis in city A with cultures positive for Streptococcus pneumoniae. METHODS: MDH staff contacted clinics and schools in city A and city B regarding conjunctivitis cases, reviewed clinical findings of conjunctivitis cases in city A and collected isolates for subtyping. RESULTS: Between September 1 and December 12, 2003, cities A and B reported 735 conjunctivitis cases. Fifty-one percent of the cases were reported from schools, childcare centers and colleges. Adults were more likely to report itching, burning or swelling of the eye(s); children were more likely to report crusty eyes (P < 0.05). Forty-nine percent of conjunctival cultures (71 of 144) were positive for S. pneumoniae. All isolates were nontypeable by serotyping. Pulsed field gel electrophoresis identified 3 clonal groups with 84% of isolates belonging to one clonal group. Multilocus sequence typing revealed that isolates had the same multilocus sequence type as isolates from a 2002 outbreak at a New England college. CONCLUSIONS: This outbreak was widespread in the community and conjunctivitis clinical presentation varied by age. The predominant strains in this outbreak were related to a pneumococcal strain implicated in prior conjunctivitis outbreaks, suggesting these strains have a predilection for causing conjunctivitis.

Multilaboratory evaluation of disk diffusion antimicrobial susceptibility testing of Neisseria meningitidis isolates.

In 2005, the Clinical and Laboratory Standards Institute published MIC interpretive criteria for 13 antimicrobial agents used for either therapy or prophylaxis of Neisseria meningitidis infections. The MIC method includes the use of lysed horse blood-supplemented Mueller-Hinton broth with incubation in 5% CO2 for 20 to 24 h. Since some clinical laboratories might prefer the option of disk diffusion testing for infrequently encountered isolates a multicenter collaborative study was conducted to evaluate the reproducibility of a disk diffusion method for testing isolates of N. meningitidis. Interpretive criteria were developed for 12 antimicrobial agents. Four laboratories tested a common collection of 50 meningococcal strains and then tested 25 unique isolates per laboratory. Isolates were tested using Mueller-Hinton sheep blood agar plates incubated for 20 to 24 h in 5% CO2; they were also tested by the reference broth microdilution method in parallel. Pooling of the MIC and disk diffusion data from the common and unique isolates provided a sufficient sample size to develop susceptible, intermediate, and resistant zone diameter interpretive criteria using the error rate-bounded method for the following agents: chloramphenicol, trimethoprim-sulfamethoxazole, ciprofloxacin, and rifampin. Due to the lack of resistant strains at the present time, "susceptible only" interpretive criteria were proposed for cefotaxime, ceftriaxone, meropenem, azithromycin, and minocycline. The numbers of minor interpretive errors with penicillin and ampicillin disk tests were unacceptably high and precluded recommended testing of those agents by the disk method. However, amdinocillin, an agent that preferentially binds to the altered penicillin binding protein responsible for diminished penicillin susceptibility, has potential utility as a surrogate screening reagent for ampicillin resistance. A disk diffusion breakpoint was derived for nalidixic acid to serve as a surrogate marker for gyrase A mutations associated with diminished fluoroquinolone susceptibility. Disk diffusion testing with meningococci can be performed in a reproducible manner with several antimicrobial agents and represents a practical and cost-effective option for testing sporadic clinical isolates or for surveillance purposes by resource-limited laboratories.

Community-associated methicillin-resistant Staphylococcus aureus, Minnesota, 2000-2003.

We compared characteristics of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs) and CA-MRSA invasive disease identified in Minnesota from 2000 through 2003. A total of 586 patients with SSTIs and 65 patients with invasive disease were identified. Patients with invasive disease were more likely to be smokers (p = 0.03), and report a history of immunosuppressive therapy (p = 0.03), emphysema (p = 0.011), or injection drug use (p = 0.020) than were SSTI patients. Invasive disease isolates were less likely to be susceptible to ciprofloxacin (p = 0.002) and clindamycin (p = 0.001) and more likely to have healthcare-associated pulsed-field gel electrophoresis subtypes than SSTI isolates (p<0.001). Patients with invasive disease may have had healthcare exposures that put them at risk of acquiring healthcare-associated MRSA and which were not exclusion criteria in the CA-MRSA case definition. Continued surveillance of MRSA is needed to better characterize CA-MRSA infections.

Outbreak of osteomyelitis/septic arthritis caused by Kingella kingae among child care center attendees.

OBJECTIVE: Kingella kingae often colonizes the oropharyngeal and respiratory tracts of children but infrequently causes invasive disease. In mid-October 2003, 2 confirmed and 1 probable case of K kingae osteomyelitis/septic arthritis occurred among children in the same 16- to 24-month-old toddler classroom of a child care center. The objective of this study was to investigate the epidemiology of K kingae colonization and invasive disease among child care attendees. METHODS: Staff at the center were interviewed, and a site visit was performed. Oropharyngeal cultures were obtained from the staff and children aged 0 to 5 years to assess the prevalence of Kingella colonization. Bacterial isolates were subtyped by pulsed-field gel electrophoresis (PFGE), and DNA sequencing of the 16S rRNA gene was performed. A telephone survey inquiring about potential risk factors and the general health of each child was also conducted. All children and staff in the affected toddler classroom were given rifampin prophylaxis and recultured 10 to 14 days later. For epidemiologic and microbiologic comparison, oropharyngeal cultures were obtained from a cohort of children at a control child care center with similar demographics and were analyzed using the same laboratory methods. The main outcome measures were prevalence and risk factors for colonization and invasive disease and comparison of bacterial isolates by molecular subtyping and DNA sequencing. RESULTS: The 2 confirmed case patients required hospitalization, surgical debridement, and intravenous antibiotic therapy. The probable case patient was initially misdiagnosed; MRI 16 days later revealed evidence of ankle osteomyelitis. The site visit revealed no obvious outbreak source. Of 122 children in the center, 115 (94%) were cultured. Fifteen (13%) were colonized with K kingae, with the highest prevalence in the affected toddler classroom (9 [45%] of 20 children; all case patients tested negative but had received antibiotics). Six colonized children were distributed among the older classrooms; 2 were siblings of colonized toddlers. No staff (n = 28) or children aged <16 months were colonized. Isolates from the 2 confirmed case patients and from the colonized children had an indistinguishable PFGE pattern. No risk factors for invasive disease or colonization were identified from the telephone survey. Of the 9 colonized toddlers who took rifampin, 3 (33%) remained positive on reculture; an additional toddler, initially negative, was positive on reculture. The children of the control child care center demonstrated a similar degree and distribution of K kingae colonization; of 118 potential subjects, 45 (38%) underwent oropharyngeal culture, and 7 (16%) were colonized with K kingae. The highest prevalence again occurred in the toddler classrooms. All 7 isolates from the control facility had an indistinguishable PFGE pattern; this pattern differed from the PFGE pattern observed from the outbreak center isolates. 16S rRNA gene sequencing demonstrated that the outbreak K kingae strain exhibited >98% homology to the ATCC-type strain, although several sequence deviations were present. Sequencing of the control center strain demonstrated more homology to the outbreak center strain than to the ATCC-type strain. CONCLUSIONS: This is the first reported outbreak of invasive K kingae disease. The high prevalence in the affected toddler class and the matching PFGE pattern are consistent with child-to-child transmission within the child care center. Rifampin was modestly effective in eliminating carriage. DNA sequence analysis suggests that there may be considerable variability within the species K kingae and that different K kingae strains may demonstrate varying degrees of pathogenicity.

Rifampin-resistant meningococcal disease.

Rifampin-resistant meningococcal disease occurred in a child who had completed rifampin chemoprophylaxis for exposure to a sibling with meningococcemia. Susceptibility testing of 331 case isolates found only 1 other case of rifampin-resistant disease in Minnesota, USA, during 11 years of statewide surveillance. Point mutations in the RNA polymerase Beta subunit (rpoB) gene were found in isolates from each rifampin-resistant case-patient.

Selection of strains for quality assessment of the disk induction method for detection of inducible clindamycin resistance in Staphylococci: a CLSI collaborative study.

A nine-laboratory collaborative study was conducted to select positive and negative quality assessment control strains for the detection of inducible clindamycin resistance in staphylococci. Four strains of Staphylococcus aureus were tested as unknowns on 10 different days in each laboratory using the recently recommended CLSI (formerly NCCLS) disk diffusion method and the inoculum purity control method. Strains contained either macrolide-lincosamide-streptogramin B (MLSB) resistance genes encoded by erm(A) or erm(C) or a macrolide resistance efflux pump encoded by msr(A). Based upon the results of this study, strain UT 32 (now designated ATCC strain BAA-977) containing erm(A) is recommended as the positive control organism for inducible clindamycin resistance. Strain UT 25 (now designated ATCC BAA-976), which harbors the efflux pump encoded by msr(A), is recommended as the negative control organism.

A high-morbidity outbreak of methicillin-resistant Staphylococcus aureus among players on a college football team, facilitated by cosmetic body shaving and turf burns.

BACKGROUND: Athletics-associated methicillin-resistant Staphylococcus aureus (MRSA) infections have become a high-profile national problem with substantial morbidity. METHODS: To investigate an MRSA outbreak involving a college football team, we conducted a retrospective cohort study of all 100 players. A case was defined as MRSA cellulitis or skin abscess diagnosed during the period of 6 August (the start of football camp) through 1 October 2003. RESULTS: We identified 10 case patients (2 of whom were hospitalized). The 6 available wound isolates had indistinguishable pulsed-field gel electrophoresis patterns (MRSA strain USA300) and carried the Panton-Valentine leukocidin toxin gene, as determined by polymerase chain reaction. On univariate analysis, infection was associated (P<.05) with player position (relative risk [RR], 17.5 and 11.7 for cornerbacks and wide receivers, respectively), abrasions from artificial grass (i.e., "turf burns"; RR, 7.2), and body shaving (RR, 6.1). Cornerbacks and wide receivers were a subpopulation with frequent direct person-to-person contact with each other during scrimmage play and drills. Three of 4 players with infection at a covered site (hip or thigh) had shaved the affected area, and these infections were also associated with sharing the whirlpool > or =2 times per week (RR, 12.2; 95% confidence interval, 1.4-109.2). Whirlpool water was disinfected with dilute povidone-iodine only and remained unchanged between uses. CONCLUSIONS: MRSA was likely spread predominantly during practice play, with skin breaks facilitating infection. Measures to minimize skin breaks among athletes should be considered, including prevention of turf burns and education regarding the risks of cosmetic body shaving. MRSA-contaminated pool water may have contributed to infections at covered sites, but small numbers limit the strength of this conclusion. Nevertheless, appropriate whirlpool disinfection methods should be promoted among athletic trainers.