Effectiveness of adjunctive rifampicin for treatment of Staphylococcus aureus bacteraemia: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To assess whether the addition of rifampicin to conventional treatment of Staphylococcus aureus bacteraemia (SAB) reduces bacteriological or clinical failure or death. DATA SOURCES: PubMed, Embase and Cochrane CENTRAL databases were searched from inception to 31 December 2022. Reference lists and PubMed citations of eligible studies were checked. REVIEW METHODS: Two study authors independently identified randomized controlled trials (RCTs) involving adult participants with SAB, in which an intervention group received adjunctive rifampicin and the control group received usual care with or without a placebo. Dichotomous data (bacteriological and clinical failure and deaths) were analysed and pooled across studies using risk ratio (RR) with 95% confidence intervals (CI) using a Mantel-Haenszel random-effect model. The key variable of interest being whether rifampicin was used. RESULTS: Six RCTs including 894 participants-of which 758 (85%) were from one trial-met the inclusion criteria. The addition of rifampicin to conventional treatment of SAB significantly reduced bacteriological failure by 59% (RR 0.41, 95% CI 0.21-0.81, I2 = 0%, number need to treat 27). However, it did not reduce clinical failure (RR 0.70, 95% CI 0.47-1.03, I2 = 0%) or deaths (RR 0.96, 95% CI 0.70-1.32, I2 = 0%). Further, it did not reduce the duration of bacteraemia, or the length of hospital stay. Adjunctive rifampicin reduced SAB recurrences (1% versus 4%, P = 0.01). Emergence of rifampicin resistance during treatment was uncommon (<1%). CONCLUSION: Although adjunctive rifampicin reduced the risk of bacteriological failure and recurrences, we found no mortality benefit to support its use in SAB.

Delusional infestation: an Australian multicentre study of 23 consecutive cases.

Delusional infestation remains a debilitating condition that is therapeutically challenging for clinicians. This case series identifies 23 patients with delusional infestation in an Australian setting. The majority of patients are women and unlikely to have a psychiatric comorbid background. The use of unnecessary anti-parasitic medication is prevalent.

Clindamycin adjunctive therapy for severe Staphylococcus aureus treatment evaluation (CASSETTE)-an open-labelled pilot randomized controlled trial.

BACKGROUND: Combination antibiotic therapy with an antitoxin agent, such as clindamycin, is included in some guidelines for severe, toxin-mediated Staphylococcus aureus infections. The evidence to support this practice is currently limited to in vitro, animal and observational human case-series data, with no previous randomized controlled trials (RCTs). OBJECTIVES: This pilot RCT aimed to determine the feasibility of conducting a clinical trial to examine if adjunctive clindamycin with standard therapy has greater efficacy than standard therapy alone for S. aureus infections. METHODS: We performed an investigator-initiated, open-label, multicentre, pilot RCT (ACTRN12617001416381p) in adults and children with severe S. aureus infections, randomized to standard antibiotic therapy with or without clindamycin for 7 days. RESULTS: Over 28 months, across nine sites, 127 individuals were screened and 34 randomized, including 11 children (32%). The primary outcome-number of days alive and free of systemic inflammatory response syndrome ≤14 days-was similar between groups: clindamycin (3 days [IQR 1-6]) versus standard therapy (4 days [IQR 0-8]). The 90 day mortality was 0% (0/17) in the clindamycin group versus 24% (4/17) in the standard therapy group. Secondary outcomes-microbiological relapse, treatment failure or diarrhoea-were similar between groups. CONCLUSIONS: As the first clinical trial assessing adjunctive clindamycin for S. aureus infections, this study indicates feasibility and that adults and children can be incorporated into one trial using harmonized endpoints, and there were no safety concerns. The CASSETTE trial will inform the definitive S. aureus Network Adaptive Platform (SNAP) trial, which includes an adjunctive clindamycin domain and participants with non-severe disease.

Interpret with caution: An evaluation of the commercial AusDiagnostics versus in-house developed assays for the detection of SARS-CoV-2 virus.

INTRODUCTION: There is limited data on the analytical performance of commercial nucleic acid tests (NATs) for laboratory confirmation of COVID-19 infection. METHODS: Nasopharyngeal, combined nose and throat swabs, nasopharyngeal aspirates and sputum was collected from persons with suspected SARS-CoV-2 infection, serial dilutions of SARS-CoV-2 viral cultures and synthetic positive controls (gBlocks, Integrated DNA Technologies) were tested using i) AusDiagnostics assay (AusDiagnostics Pty Ltd); ii) in-house developed assays targeting the E and RdRp genes; iii) multiplex PCR assay targeting endemic respiratory viruses. Discrepant SARS-CoV-2 results were resolved by testing the N, ORF1b, ORF1ab and M genes. RESULTS: Of 52 clinical samples collected from 50 persons tested, respiratory viruses were detected in 22 samples (42 %), including SARS CoV-2 (n = 5), rhinovirus (n = 7), enterovirus (n = 5), influenza B (n = 4), hMPV (n = 5), influenza A (n = 2), PIV-2 (n = 1), RSV (n = 2), CoV-NL63 (n = 1) and CoV-229E (n = 1). SARS-CoV-2 was detected in four additional samples by the AusDiagnostics assay. Using the in-house assays as the "gold standard", the sensitivity, specificity, positive and negative predictive values of the AusDiagnostics assay was 100 %, 92.16 %, 55.56 % and 100 % respectively. The Ct values of the real-time in-house-developed PCR assay targeting the E gene was significantly lower than the corresponding RdRp gene assay when applied to clinical samples, viral culture and positive controls (mean 21.75 vs 28.1, p = 0.0031). CONCLUSIONS: The AusDiagnostics assay is not specific for the detection SARS-CoV-2. Any positive results should be confirmed using another NAT or sequencing. The case definition used to investigate persons with suspected COVID-19 infection is not specific.

Rapid, highly discriminatory binary genotyping to demonstrate methicillin-resistant Staphylococcus aureus transmission in a tertiary care intensive care unit.

OBJECTIVES: No previous studies of methicillin-resistant Staphylococcus aureus (MRSA) epidemiology in adult intensive care units (ICUs) have assessed the utility of rapid, highly discriminatory strain typing in the investigation of transmission events. DESIGN: Observational. SETTING: A 22-bed medical-surgical adult ICU. Patients Those admissions MRSA-positive on initial screening and all admissions <48 hours in duration were excluded, leaving a cohort of 653 patients (median age, 61 years; APACHE-II, 19). METHODS: We conducted this study of MRSA transmission over 1 year (August 1, 2011 to July 31, 2012) using a multiplex PCR-based reverse line blot (mPCR/RLB) assay to genotype isolates from surveillance swabs obtained at admission and twice weekly during ICU stays. MRSA prevalence and incidence rates were calculated and transmission events were identified using strain matching. Colonization pressure was calculated daily by summation of all MRSA cases. RESULTS: Of 1,030 admissions to ICU during the study period, 349 patients were excluded. MRSA acquisition occurred during 31 of 681 (4.6%) remaining admissions; 19 of 31(61%) acquisitions were genotype-confirmed, including 7 (37%) due to the most commonly transmitted strain. Moving averages of MRSA patient numbers on the days prior to a documented event were used in a Poisson regression model. A significant association was found between transmission and colonization pressure when the average absolute colonization pressure on the previous day was ≥3 (χ2=7.41, P=0.01). CONCLUSIONS: mPCR/RLB characterizes MRSA isolates within a clinically useful time frame for identification of single-source clusters within the ICU. High MRSA colonization pressure (≥3 MRSA-positive patients) on a given day is associated with an increased likelihood of a transmission event.

Histoplasmosis in Australia: a report of a case with a review of the literature.

Histoplasmosis is a rare but serious fungal infection commonly presenting as mucosal ulceration of the oral cavity. It is increasingly recognized in Australia but the source of infection remains obscure and it is likely to be under-diagnosed. We report a case of chronic mucosal ulceration which failed to fully respond to periodontal therapy. Histology and culture of a gingival biopsy was consistent with histoplasmosis, and the patient responded favourably to treatment with oral itraconazole. Histoplasmosis may present to general dental practitioners as chronic mucosal ulceration and should be considered in the differential diagnosis of such lesions. Diagnosis is best made by culture and histology of biopsy specimens.

Emergence and control of an outbreak of infections due to Panton-Valentine leukocidin positive, ST22 methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit.

Methicillin resistant Staphylococcus aureus (MRSA) infection can cause significant morbidity and mortality in neonates. We investigated a nosocomial MRSA outbreak in a neonatal intensive care unit (NICU), using a novel typing method. Following two fatal cases, in May 2011, a prospective outbreak investigation was conducted, involving neonates, mothers and healthcare workers in a large tertiary NICU in Sydney. MRSA isolates were characterized by antimicrobial susceptibility testing, a multiplex PCR-based reverse line blot (mPCR/RLB) binary typing system and other molecular typing methods. Over 7 months, 14 neonates were colonized with MRSA and six infected: three with superficial lesions and three with life-threatening disease, including the two index cases, who died despite empirical treatment with vancomycin. Isolates from 15 neonates were indistinguishable by RLB typing and identified as a PVL-producing ST22 SCCmec IV MRSA strain, which was resistant to gentamicin and trimethoprim-sulphamethoxazole. The outbreak strain was also isolated from one healthcare worker, one environmental swab and one father, but the source remained obscure. During the same period several different non-multiresistant and multiresistant MRSA strains were isolated from five neonates, five mothers (including two whose infants were colonized with the outbreak strain), one father, three healthcare workers and two environmental swabs. Rapid turnaround time of typing results allowed us to recognize and define the outbreak and implement targeted infection control interventions. PVL-producing ST22 SCCmec IV MRSA appears to be a virulent and highly transmissible pathogen in the NICU, which was difficult to control.

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.

Feedback to clinicians on preventable factors can reduce hospital onset Staphylococcus aureus bacteraemia rates.

Staphylococcus aureus bacteraemia (SAB) is associated with significant morbidity and mortality, yet there are limited data on preventable factors. This study aimed to evaluate SAB episodes at a tertiary care hospital; to identify factors that, if avoided, might have prevented the episode of SAB; and to provide feedback to treating clinicians. Of 187 episodes of SAB over 19 months 59.9% were caused by meticillin-susceptible S. aureus (MSSA) and 40.1% meticillin-resistant S. aureus (MRSA), 65.8% of SAB were healthcare-associated (HA) and 34.2% were community-acquired. Seven- and 30-day mortality rates, overall, were 11.2% and 20.9% respectively. At least one preventable factor was identified in 50.4% of HA-SAB episodes, including recent nosocomial MRSA acquisition in 53.7% MRSAB episodes and one or more factors associated with intravenous access in at least 24.3% of HA (35.7% of hospital onset) cases. SAB was more likely to be associated with at least one identifiable, preventable factor in surgical than in medical inpatients (86.2% vs 54.5%, P=0.004). Patients with HA-MRSAB were more likely than those with HA-MSSAB to require intensive care unit admission (44.4% vs 18.8%, P=0.003). Identifying and addressing preventable factors will better target resources for prevention of SAB. Feedback about preventable factors was associated with a reduction in HA-SAB rates from 0.29 to 0.20 per 1000 occupied bed-days, from 2008 to 2009.