David J. Hetem

Transmissibility of Livestock-associated Methicillin-Resistant Staphylococcus aureus

Previous findings have suggested that the nosocomial transmission capacity of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is lower than that of other MRSA genotypes. We therefore performed a 6-month (June 1–November 30, 2011) nationwide study to quantify the single-admission reproduction number, RA, for LA-MRSA in 62 hospitals in the Netherlands and to compare this transmission capacity to previous estimates. We used spa typing for genotyping. Quantification of RA was based on a mathematical model incorporating outbreak sizes, detection rates, and length of hospital stay. There were 141 index cases, 40 (28%) of which were LA-MRSA. Contact screening of 2,101 patients and 7,260 health care workers identified 18 outbreaks (2 LA-MRSA) and 47 secondary cases (3 LA-MRSA). RA values indicated that transmissibility of LA-MRSA is 4.4 times lower than that of other MRSA (not associated with livestock).

Nosocomial transmission of community-associated methicillin-resistant Staphylococcus aureus in Danish Hospitals

OBJECTIVES The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has changed the epidemiology of MRSA infections worldwide. In contrast to hospital-associated MRSA (HA-MRSA), CA-MRSA more frequently affects healthy individuals, both with and without recent healthcare exposure. Despite obvious epidemiological differences, it is unknown whether differences in nosocomial transmissibility exist. We have, therefore, quantified the transmissibility, expressed by the single admission reproduction number (R(A)), of CA-MRSA and HA-MRSA in hospital settings in Denmark. METHODS MRSA index cases and secondary cases were investigated in four hospitals in the Copenhagen area. Index cases were defined as non-isolated, non-screened patients with MRSA, and secondary cases were defined as persons carrying MRSA isolates-identical to that of the corresponding index-as identified through contact screening. CA-MRSA and HA-MRSA were categorized upon genotyping [CA-MRSA: t008-ST8, PVL+; t019-ST30, PVL+; t127-ST1, PVL+; t044-ST80, PVL+; and their related spa types; and HA-MRSA: all other (where ST stands for sequence type and PVL stands for Panton-Valentine leucocidin)]. A mathematical model was applied to determine the genotype-specific transmission rate (i.e. R(A)) of CA-MRSA and HA-MRSA strains. RESULTS During the 7 year study period there were 117 MRSA index cases with subsequent post-contact screening (of 1108 patients and healthcare workers), revealing 22 outbreaks with a total of 52 secondary patients. R(A) values were 0.07 (95% CI 0.00-0.28) and 0.65 (95% CI 0.48-0.84) for CA-MRSA and HA-MRSA, respectively. CONCLUSIONS In four Danish hospitals the nosocomial transmission rate of CA-MRSA was 9.3 times lower than that of HA-MRSA.

Emergence of High-Level Mupirocin Resistance in Coagulase-Negative Staphylococci Associated with Increased Short-Term Mupirocin Use

ABSTRACT In our hospital, mupirocin has increasingly been used for peri-operative decolonization of Staphylococcus aureus. The target for mupirocin is isoleucyl tRNA synthetase (ileS). High-level resistance to mupirocin is conferred by acquisition of plasmids expressing a distinct ileS gene (ileS2). Here we evaluated the longitudinal trends in high-level mupirocin resistance in coagulase-negative staphylococci (CoNS) and linked this to the presence of ileS2 genes and mupirocin use. We assessed mupirocin resistance in CoNS bloodstream isolates from 2006 to 2011 tested by Phoenix automated testing (PAT). We evaluated the reliability of PAT results using Etest. PAT species determination was confirmed by MALDI-TOF (matrix-assisted laser desorption ionization–time of flight) mass spectrometry. We investigated the presence of ileS2 in the first 100 consecutive CoNS bloodstream isolates of each year using RT-PCR. Mupirocin use increased from 3.6 kg/year in 2006 to 13.3 kg/year in 2010 and correlated with the increase in the percentage of CoNS isolates carrying ileS2 (8% in 2006 to 22% in 2011; Spearmans rho, 0.137; P = 0.01). The sensitivity and specificity of PAT for detecting high-level mupirocin resistance were 0.97 and 0.97, respectively. ileS2 was detected in 81 of 82 phenotypically highly mupirocin-resistant strains and associated with resistance to ciprofloxacin, erythromycin, and clindamycin. In conclusion, we found a rapid increase in high-level resistance to mupirocin and resistance to other antibiotics in CoNS associated with an increase in mupirocin use. The associated resistance to other antibiotics may result in a reduction of oral antibiotic options for prolonged treatment of prosthetic infections with CoNS.

Prevention of Surgical Site Infections: Decontamination With Mupirocin Based on Preoperative Screening for Staphylococcus aureus Carriers or Universal Decontamination?

Perioperative decolonization of Staphylococcus aureus nasal carriers with mupirocin together with chlorhexidine body washing reduces the incidence of S. aureus surgical site infection. A targeted strategy, applied in S. aureus carriers only, is costly, and implementation may reduce effectiveness. Universal decolonization is more cost-effective but increases exposure of noncarriers to mupirocin and the risk of resistance to mupirocin in staphylococci. High-level mupirocin resistance in S. aureus can emerge through horizontal gene transfer originating from coagulase-negative staphylococci (CoNS) and through clonal transmission. The current evidence on the occurrence of high-level mupirocin resistance in S. aureus and CoNS, in combination with the results of mathematical modeling, strongly suggests that the increased selection of high-level mupirocin resistance in CoNS does not constitute an important risk for high-level mupirocin resistance in S. aureus. Compared with a targeted strategy, universal decolonization seems associated with an equally low risk of mupirocin resistance in S. aureus.

Acquisition of high-level mupirocin resistance in CoNS following nasal decolonization with mupirocin

OBJECTIVES The association between mupirocin use and plasmid-based high-level resistance development mediated through mupA in CoNS has not been quantified. We determined acquisition of mupirocin resistance in Staphylococcus aureus and CoNS in surgery patients treated peri-operatively with mupirocin. PATIENTS AND METHODS Patients admitted for surgery were treated with nasal mupirocin ointment and chlorhexidine soap for 5 days, irrespective of S. aureus carrier status. Nasal swabs were obtained before decolonization (T1) and 4 days after surgery (T2) and were inoculated onto agars containing 8 mg/L mupirocin. Staphylococci were identified by MALDI-TOF MS and mupirocin resistance was confirmed by Etest. RESULTS Among 1578 surgical patients, 936 (59%) had nasal swabs obtained at T1 and T2; 192 (21%) patients carried mupirocin-resistant CoNS at T1 and 406 (43%) at T2 (P<0.001). Of 744 patients not colonized at T1, 277 acquired resistance (37%), corresponding to an acquisition rate of 7.4/100 patient days at risk. In all, 588 (97%) of 607 mupirocin-resistant CoNS had an MIC >256 mg/L (high level) and 381 of 383 (99.5%) were mupA positive. No acquisition of mupirocin resistance was observed in S. aureus. CONCLUSIONS Acquisition of mupirocin resistance following decolonization was widespread in CoNS and absent in S. aureus. As almost all isolates harboured the mupA gene, monitoring resistance development in S. aureus when decolonization strategies containing mupirocin are used is recommended.

Molecular epidemiology of MRSA in 13 ICUs from eight European countries

OBJECTIVES The European epidemiology of MRSA is changing with the emergence of community-associated MRSA (CA-MRSA) and livestock-associated MRSA (LA-MRSA). In this study, we investigated the molecular epidemiology of MRSA during 2 years in 13 ICUs in France, Greece, Italy, Latvia, Luxemburg, Portugal, Slovenia and Spain. METHODS Surveillance cultures for MRSA from nose and wounds were obtained on admission and twice weekly from all patients admitted to an ICU for ≥3 days. The first MRSA isolate per patient was genotyped in a central laboratory by MLST, spa typing, agr typing and SCCmec (sub)typing. Risk factors for patients with an unknown history of MRSA colonization were identified. RESULTS Overall, 14 390 ICU patients were screened, of whom 8519 stayed in an ICU for ≥3 days. Overall MRSA admission prevalence was 3.9% and ranged from 1.0% to 7.0% for individual ICUs. Overall MRSA acquisition rate was 2.5/1000 patient days at risk and ranged from 0.2 to 8/1000 patient days at risk per ICU. In total, 557 putative MRSA isolates were submitted to the central laboratory for typing, of which 511 (92%) were confirmed as MRSA. Each country had a distinct epidemiology, with ST8-IVc (UK-EMRSA-2/-6, USA500) being most prevalent, especially in France and Spain, and detected in ICUs in five of eight countries. Seventeen (3%) and three (<1%) isolates were categorized as CA-MRSA and LA-MRSA, respectively. Risk factors for MRSA carriage on ICU admission were age >70 years and hospitalization within 1 year prior to ICU admission. CONCLUSIONS The molecular epidemiology of MRSA in 13 European ICUs in eight countries was homogeneous within, but heterogeneous between, countries. CA-MRSA and LA-MRSA genotypes and Panton-Valentine leucocidin-producing isolates were detected sporadically.

Relationship between bacterial colonization of external cerebrospinal fluid drains and secondary meningitis: a retrospective analysis of an 8-year period

OBJECT A frequent complication of CSF drains is secondary meningitis. This study was designed to assess the predictive value of a positive culture from a CSF drain tip for the development of secondary meningitis. METHODS The authors conducted a retrospective study of an 8-year period in which patients were treated in a tertiary care hospital in The Netherlands. Patients with positive cultures from CSF drain tips were identified from the microbiology database. Patient charts were reviewed to retrieve demographic, clinical, and laboratory data. Statistical analysis was performed using multivariate logistic regression to determine significant risk factors for the development of secondary meningitis. RESULTS A total of 139 patients with positive CSF-drain cultures were included; 72 patients (52%) suffered secondary meningitis at the time of CSF drain removal, or developed it consecutively. Development of secondary meningitis was associated with use of ventricular drains (OR 3.4 vs lumbar drains; 95% CI 1.7-6.8), with age less than 18 years (OR 4.7; 95% CI 1.3-17.3), and with colonization with Staphylococcus aureus (OR 3.1 vs other microorganisms; CI 1.2-8.5). Thirty-two patients (44% of total secondary meningitis) were diagnosed with secondary meningitis 24 hours or more after CSF drain removal; in 13 patients (18%) the diagnosis was made after 48 hours or more. CONCLUSIONS Positive CSF-drain cultures are strongly associated with development of secondary meningitis. A positive CSF-drain culture may precede clinical symptoms and should therefore be communicated to the treating physician by the microbiological laboratory as soon as possible, and prophylactic antibiotic therapy should be considered.