James O. Robinson

Antibiotic Choice May Not Explain Poorer Outcomes in Patients With Staphylococcus aureus Bacteremia and High Vancomycin Minimum Inhibitory Concentrations

BACKGROUND There are concerns about reduced efficacy of vancomycin in patients with Staphylococcus aureus bacteremia (SAB), especially when the minimum inhibitory concentration (MIC) nears the upper limit of the susceptible range. METHODS We examined the relationship between antibiotic treatment, 30-day mortality, and microbiologic parameters in a large Australasian cohort of patients with SAB. RESULTS We assessed 532 patients with SAB from 8 hospitals. All patients with methicillin-resistant S. aureus (MRSA) bacteremia were treated with vancomycin, and patients with methicillin-susceptible S. aureus (MSSA) bacteremia received either flucloxacillin or vancomycin. Increasing vancomycin MIC was associated with increased mortality in vancomycin-treated patients. However, even in patients with MSSA bacteremia treated with flucloxacillin, mortality was also higher if the vancomycin Etest MIC of their isolate was >1.5 μg/mL, compared with those with lower MIC isolates (26.8% vs 12.2%; P < .001). After adjustment in a multivariate model, age, hospital-onset SAB and vancomycin MIC were independently associated with mortality, but methicillin resistance and antibiotic choice were not. CONCLUSIONS We have confirmed an association between higher vancomycin MIC and increased mortality in patients with SAB, but surprisingly this relationship was not related to the antibiotic treatment received, suggesting that the use of vancomycin per se is not responsible for the poorer outcome.

Community-Acquired Pneumonia Due to Pandemic A(H1N1)2009 Influenzavirus and Methicillin Resistant Staphylococcus aureus Co-Infection

Background Bacterial pneumonia is a well described complication of influenza. In recent years, community-onset methicillin-resistant Staphylococcus aureus (cMRSA) infection has emerged as a contributor to morbidity and mortality in patients with influenza. Since the emergence and rapid dissemination of pandemic A(H1N1)2009 influenzavirus in April 2009, initial descriptions of the clinical features of patients hospitalized with pneumonia have contained few details of patients with bacterial co-infection. Methodology/Principal Findings Patients with community–acquired pneumonia (CAP) caused by co-infection with pandemic A(H1N1)2009 influenzavirus and cMRSA were prospectively identified at two tertiary hospitals in one Australian city during July to September 2009, the period of intense influenza activity in our region. Detailed characterization of the cMRSA isolates was performed. 252 patients with pandemic A(H1N1)2009 influenzavirus infection were admitted at the two sites during the period of study. Three cases of CAP due to pandemic A(H1N1)2009/cMRSA co-infection were identified. The clinical features of these patients were typical of those with S. aureus co-infection or sequential infection following influenza. The 3 patients received appropriate empiric therapy for influenza, but inappropriate empiric therapy for cMRSA infection; all 3 survived. In addition, 2 fatal cases of CAP caused by pandemic A(H1N1)2009/cMRSA co-infection were identified on post–mortem examination. The cMRSA infections were caused by three different cMRSA clones, only one of which contained genes for Panton-Valentine Leukocidin (PVL). Conclusions/Significance Clinicians managing patients with pandemic A(H1N1)2009 influenzavirus infection should be alert to the possibility of co-infection or sequential infection with virulent, antimicrobial-resistant bacterial pathogens such as cMRSA. PVL toxin is not necessary for the development of cMRSA pneumonia in the setting of pandemic A( H1N1) 2009 influenzavirus co-infection.

Community-associated versus healthcare-associated methicillin-resistant Staphylococcus aureus bacteraemia: A 10-year retrospective review

The objective was to compare the epidemiology and outcome of healthcare- (HA-) and community-associated (CA-) MRSA bacteraemia. A 10-year retrospective study of MRSA bacteraemia was carried out. Episodes were classified according to established criteria. Molecular typing was performed on a subset of isolates. Of 197 MRSA bacteraemia episodes, 178 (90.4%) were classified as HA-MRSA and 19 (9.6%) as CA-MRSA. All-cause 7- and 30-day mortality rates were similar in the HA and CA-MRSA bacteraemia groups; however, 1-year mortality was higher in the HA-MRSA bacteraemia group (48.3% vs 21.1% [p = 0.023]). Thirty-day all-cause mortality was significantly lower if empiric antimicrobial therapy included agent(s) to which the isolate tested susceptible, compared with patients receiving “inactive” therapy (19% vs 35.1% [p = 0.011]). The majority of MRSA bacteraemia episodes were caused by clones known to circulate in the community. All-cause mortality is as high in HA- as in CA-MRSA bacteraemia. Thirty-day mortality was significantly reduced if the patient received an antibiotic with activity against the MRSA isolate.

A comparison of long-term outcomes after meticillin-resistant and meticillin-sensitive Staphylococcus aureus bacteraemia: an observational cohort study

BACKGROUND Findings from previous studies have suggested that outcomes after meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia are worse than after meticillin-sensitive S. aureus (MSSA) bacteraemia. We assessed whether patients who had MRSA bacteraemia had a higher risk of death and recurrent infections than those who had MSSA bacteraemia. METHODS For this observational cohort study, we assessed data from the microbiology laboratory database at the Royal Perth Hospital (WA, Australia). Data were for all patients who had an episode of MRSA bacteraemia between July 1, 1997, and June 30, 2007, and, by use of a computer-generated randomisation sequence, a randomly selected subgroup of patients who had an episode of MSSA bacteraemia (patients with one or more set of blood cultures positive for S. aureus). The primary outcomes were survival time and subsequent infection-related hospital readmissions, analysed by Cox proportional hazards regression with adjustment for important prognostic factors. FINDINGS Of the 583 patients who had an episode of MRSA or MSSA bacteraemia, we used data for the 582 who had complete data linkage: 185 patients who had MRSA bacteraemia and 397 patients who had MSSA bacteraemia. The crude survival time of patients after MRSA bacteraemia was shorter than it was for patients with MSSA bacteraemia (14 months [IQR 1-86] vs 54 months [3-105]; hazard ratio 1·46, 95% CI 1·18-1·79; p=0·01). The adverse association between MRSA and all-cause mortality (0·98, 0·77-1·30; p=0·87) or infection-related mortality (1·22, 0·89-1·69; p=0·22) were not statistically significant after adjustment for important prognostic factors including age, comorbidities, severity of acute illness, metastatic infections, and long-term care facility resident status. After adjustment for these confounding factors, we saw no difference in infection-related hospital readmissions between patients who had MRSA bacteraemia and those who had MSSA bacteraemia (odds ratio 0·95, 95% CI 0·59-1·53; p=0·83). INTERPRETATION Long-term outcomes after MRSA bacteraemia were worse than those after MSSA bacteraemia through its confounding associations with other prognostic factors. Our findings might have implications for management strategies to control MRSA colonisation. FUNDING The Medical Research Foundation of Royal Perth Hospital.

Vancomycin minimum inhibitory concentration, host comorbidities and mortality in staphylococcus aureus bacteraemia

We reported an association between elevated vancomycin MIC and 30-day mortality in patients with Staphylococcus aureus bacteraemia (SAB), including patients with methicillin-susceptible S. aureus (MSSA) treated with flucloxacillin. A detailed analysis of comorbidities and disease severity scores in the same cohort of patients was performed to ascertain if unknown clinical parameters may have influenced these results. The association between elevated vancomycin MIC and 30-day mortality in SAB remained significant (p 0.001) on multivariable logistic regression analysis even when accounting for clinical factors. In addition, the association persisted when restricting analysis to patients with MSSA bacteraemia treated with flucloxacillin. This suggests that elevated vancomycin MIC is associated with but not causally linked to an organism factor that is responsible for increased mortality.

Prevalence of nasal methicillin-resistant Staphylococcus aureus colonization in healthcare workers in a Western Australian acute care hospital.

Due to a longstanding comprehensive “search and destroy policy”, methicillin-resistant Staphylococcus aureus (MRSA) is not endemic in Western Australian (WA) acute care hospitals. As the prevalence of MRSA in the community has increased, healthcare workers (HCW) are at risk of importing MRSA into hospitals. We aimed to determine the prevalence of and risk factors for nasal MRSA colonization in our HCW population. A period prevalence study was conducted at an 850-bed tertiary hospital. Basic demographics and a nasal swab were obtained. A total of 1,542 HCWs employed in our centre were screened for MRSA, of whom 3.4% (n = 52) were colonized. MRSA colonization was more common in patient care assistants (6.8%) and nurses (5.2%) than in allied health professionals (1.7%) and doctors (0.7%) (p < 0.01). Working in “high-risk” wards that cared for MRSA colonized/infected patients was the strongest risk factor for HCW MRSA colonization (p < 0.001). ST1-IV and ST78-IV (the most common community clones in the region) were the most frequently identified clones. In conclusion, MRSA colonization of HCWs occurs primarily in HCWs caring for patients colonized or infected with MRSA. Surveillance screening of HCWs should be regularly performed on wards with patients with high MRSA colonization prevalence to prevent further spread in the hospital.

Increased EMRSA-15 health-care worker colonization demonstrated in retrospective review of EMRSA hospital outbreaks

BackgroundHealth care worker (HCW) colonization with methicillin resistant Staphylococcus aureus (MRSA) is a documented cause of hospital outbreaks and contributes to ongoing transmission. At Royal Perth Hospital (RPH) it had been anecdotally noted that the increasing prevalence of EMRSA-15 appeared to be associated with increased HCW colonization compared with Aus2/3-EMRSA. Hence we compared HCW colonization rates during outbreaks of EMRSA-15 and Aus2/3-EMRSA at a single institution.MethodsWe performed a retrospective review of EMRSA-15 and Aus2/3-EMRSA outbreaks from 2000–2009 at RPH, a quaternary hospital in Western Australia. Outbreak files were reviewed and relevant data extracted.ResultsTen EMRSA-15 outbreaks were compared with seven Aus2/3 outbreaks. The number of patients colonized was similar between EMRSA-15 and Aus2/3-EMRSA outbreaks (median 7 [range 3–20] and 11 [5–26], respectively; P = 0.07) but the number of HCWs colonized was significantly higher in EMRSA-15 outbreaks compared to Aus2/3-EMRSA outbreaks (median 4 [range 0–15] and 2 [1-3], respectively; P = 0.013). The percentage of HCWs colonized was also higher in EMRSA-15 outbreaks versus Aus2/3-EMRSA outbreaks (median 3.4% [range 0–5.5%] and 0.81% [0.56–2.2%], respectively; P = 0.013).ConclusionsThis study demonstrates a higher level of HCW colonization during EMRSA-15 outbreaks compared with Aus2/3-EMRSA outbreaks. This finding suggests that MRSA vary in their ability to colonize HCWs and contribute to outbreaks. MRSA type should be determined during outbreaks and future research should investigate the mechanisms by which EMRSA-15 contributes to increased HCW colonization.

Intrafamilial transmission of methicillin-resistant Staphylococcus aureus.

To the Editor: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection was first described in our region over 15 years ago (1). More recently, CA-MRSA has become a global concern and is now a common cause of skin and soft tissue infections in the United States (2). An association between severe CA-MRSA infection (e.g., necrotizing fasciitis and pneumonia) and the synergohymenotrophic exotoxin Panton-Valentine leukocidin (PVL) has been made (3,4). Reports have documented CA-MRSA transmission among household members; however, most cases have been mild or moderate infections or asymptomatic colonization (5–7). We describe intrafamilial transmission of a PVL-containing CA-MRSA clone common in Australia (ST30-MRSA-IV) between a nurse who suffered recurrent abscesses and her husband, who died of severe pneumonia. In July 2006, a 61-year-old previously healthy nurse (Mrs A) sought treatment for an infected seborrheic cyst of the scalp. Culture of pus yielded MRSA that was susceptible to clindamycin. She was treated with oral clindamycin. After resolution of the infection, topical MRSA decolonization therapy with 3% hexachlorophane body wash (daily), 20% cetrimide shampoo (3×/wk), and 2% mupirocin nasal ointment (3×/d) was administered for 10 days, as per our institutional protocol for MRSA-colonized healthcare workers. Subsequently, MRSA surveillance swabs from the nose, throat, and scalp obtained weekly for 10 weeks and cultured on selective MRSA chromogenic agar and in selective broth enrichment media were negative. Household members were not screened for MRSA colonization. Six months later, in January 2007, the patient’s husband (Mr A), a 60-year-old smoker who was her only household contact, was admitted with a 1-day history of dyspnea, pleuritic chest pain, cough with sputum, fever, vomiting, and diarrhea. On admission, he was unwell, with tachycardia (pulse rate 132 bpm), hypotension (95/60 mm Hg), tachypnea (40 breaths/min), and hypoxia (oxygen saturation 93% on 15 L O2/min). A chest radiograph showed bilateral infiltrates and a right pleural effusion. He was diagnosed with community-acquired pneumonia and treated with intravenous ceftriaxone and azithromycin as per local protocol. However, within 12 hours, his condition deteriorated, necessitating admission to the intensive care unit for ventilation and inotropic support. Broncho-alveolar lavage (BAL) fluid demonstrated gram-positive cocci in tetrads, and intravenous vancomycin and dicloxacillin were added to therapy. Despite aggressive supportive measures, Mr A’s condition continued to deteriorate, and he died 28 hours after admission. MRSA was subsequently cultured from blood, sputum, and BAL fluid; an autopsy was not performed. In June 2007, Mrs A sought treatment for an abscess with cellulitis on the left thigh. The abscess was surgically drained, and cultures again yielded MRSA. She was treated with intravenous and oral clindamycin for 10 days and subsequently underwent repeat MRSA decolonization therapy; again, swabs taken 1×/wk for 10 weeks postdecolonization were negative. Molecular typing of the MRSA isolates obtained from Mrs A at the time of her initial skin infection, Mr A’s blood culture, and Mrs A’s second skin infection was performed by using contour-clamped homogenous electric field electrophoresis (CHEF) according to a previously described method (8) (Figure). The CHEF patterns were indistinguishable and were identical to the known CHEF pattern for ST30-MRSA-IV (9). All 3 isolates contained the lukF-PV/lukS-PV genes that encode PVL and had the same antibiogram (i.e., isolates were resistant only to β-lactam antimicrobial agents). Figure Contour-clamped homogenous electric field electrophoresis of Staphylococcus aureus isolates. Lanes 2, 3, and 4 (Sma1 restriction): methicillin-resistant S. aureus (MRSA) isolated from Mrs A’s first infection, Mr A’s blood culture, and ... We describe intrafamilial MRSA transmission (defined as >2 family members who live at the same postal address and who are colonized or infected with a MRSA strain having the same CHEF pattern) that resulted in a fatal outcome. The MRSA strain responsible (ST30-MRSA-IV, or Western Samoan phage pattern/Oceania strain MRSA) is a common cause of CA-MRSA infection in Australia. Recurrent MRSA infection developed in Mrs A several months after completion of apparently successful MRSA decolonization therapy. We could not determine whether this recurrence was because of persistent MRSA colonization not detected by surveillance (e.g., perineal or gastrointestinal colonization) or whether Mrs A was successfully decolonized but Mr A’s colonization/infection resulted in recolonization and subsequent infection. Whatever the explanation, this case highlights a potential weakness in MRSA surveillance programs that rely on short-term, limited-site surveillance. A comprehensive MRSA search-and-destroy policy in place for over 25 years has prevented MRSA from becoming endemic in our institution (10). However, the rapidly changing epidemiology of MRSA in becoming a predominantly community pathogen represents a significant challenge to the ongoing success of this policy. In response to this challenge, the Western Australian Department of Health has implemented a community-based MRSA search-and-destroy program for patients with MRSA infection caused by exotic PVL-positive clones (e.g., ST30-MRSA-IV, ST93-MRSA-IV, ST80-MRSA-IV, and ST8-MRSA-IV/USA300). This program includes treatment/decolonization therapy for the index case, screening of household members for MRSA infection/colonization, and simultaneous treatment/decolonization if MRSA is identified. Although a similar approach has proved successful in Denmark (6), whether this success can be sustainable on a larger scale remains to be seen.