Antimicrobial stewardship audit and feedback rounds: the impact of electronic systems and moving beyond the restricted antibiotic list.

BACKGROUND: Current methods of antimicrobial usage surveillance have limited efficacy in changing practice due to delayed reporting to clinicians and the inability to stratify by medical specialty. This study was undertaken in a tertiary teaching hospital with a well established antimicrobial stewardship (AMS) programme and electronic medicines management (eMM) system in Sydney, Australia. AIMS: To describe and analyse the implementation of a novel AMS audit and feedback method, in the context of an eMM system. METHODS: The AMS team conducted the audit weekly, and the study design was a prospective, observational study. All acute, adult inpatients were included in this intervention. All active systemic antimicrobial prescriptions on the day of the rounds were included. RESULTS: The prevalence of patients on antimicrobial therapy was 37%. The median time taken per round was 44 min for eMM compared to 58 min for paper. All key performance indicators improved over the study period. Appropriateness compared to guidelines increased from 55% to 71%, and documentation of an indication increased from 75% to 98%. There were 1413 recommendations made, with the most common being to cease an antimicrobial agent. The recommendation uptake rate was 47% at 24 h post-round. CONCLUSIONS: AMS rounds are an effective tool for auditing and providing feedback on antimicrobial use and should include all antimicrobials rather than solely 'restricted' agents. These rounds had a high uptake rate, improvements in the appropriateness of antimicrobial use, and a planned duration or review date. A benefit of eMM was improvement in the documentation of indication for antimicrobial agents, and reduced time taken to audit.

A multicentre outbreak of ST45 MRSA containing deletions in the spa gene in New South Wales, Australia.

BACKGROUND: Early identification of MRSA by diagnostic medical microbiology laboratories enables improved antimicrobial choice and outcomes. The Cepheid Xpert® MRSA/SA BC test rapidly identifies Staphylococcus aureus bloodstream infections through spa gene detection and methicillin resistance via mecA gene detection. Recent emergence of S. aureus with deletions in the spa gene has resulted in false-negative results for this test, leading to misidentification of infections with this organism, particularly MRSA ST45. OBJECTIVES: To investigate the emergence and prevalence of ST45 MRSA in New South Wales (NSW), Australia. METHODS: WGS read data from six NSW hospitals were collected for 131 ST45 MRSA isolates and analysed. RESULTS: Of the 131 ST45 MRSA investigated, 88.5% (116/131) contained a deletion in the spa gene that appeared to have arisen once in approximately 2010 followed by clonal expansion. Given the successful establishment of this 'spa-deletion' MRSA clone, the Cepheid Xpert® MRSA/SA BC test became unreliable for confirming S. aureus bacteraemia in NSW. Subsequently, the algorithm used by this test has been updated and evaluated to take into account the presence of S. aureus with either a spa deletion or SCCmec target variations. CONCLUSIONS: This study highlighted the applied use of WGS for assessing diagnostic assays and informing necessary changes to ensure the viability of the Cepheid Xpert® MRSA/SA BC test in the context of the new 'spa-deletion' MRSA clone. It demonstrated how continued surveillance through WGS can reveal evolutionary events that may impact diagnostic assays, allowing corrective modifications to be made in real time.

Identification of a novel lineage of plasmids within phylogenetically diverse subclades of IncHI2-ST1 plasmids.

IncHI2-ST1 plasmids play an important role in co-mobilizing genes conferring resistance to critically important antibiotics and heavy metals. Here we present the identification and analysis of IncHI2-ST1 plasmid pSPRC-Echo1, isolated from an Enterobacter hormaechei strain from a Sydney hospital, which predates other multi-drug resistant IncHI2-ST1 plasmids reported from Australia. Our time-resolved phylogeny analysis indicates pSPRC-Echo1 represents a new lineage of IncHI2-ST1 plasmids and show how their diversification relates to the era of antibiotics.

Is a 10-minute surgical scrub necessary in urologic prosthetic surgery? A randomized study of the effect of a 5- vs 10-minute surgical scrub on bacterial colony counts in the genital skin.

AIMS: To determine the antiseptic efficacy on bacterial colony counts of a 5- vs 10-minute surgical site scrub in urologic surgery. METHODS: A prospective cohort study was conducted in 101 patients presenting for elective urological procedures. Patients were randomized to a 5- or 10-minute groin scrub with Betadine (povidone-iodine). Skin swabs were taken immediately after skin clipping and following routine painting with Betadine. A third swab was taken after the betadine skin scrub. Bacterial colony counts were reported as a number of colony-forming units (CFUs). The primary outcome measure was a quantitative comparison of CFUs in the two arms. RESULTS: Fifty-three patients were randomized to a 5-minute scrub and 48 to a 10-minute scrub. After Betadine painting, CFUs were present in 38% of patients in the 5-minute group (mean, 33.5 CFU) and in 27% of the 10-minute group (mean, 45.4 CFU). Following the surgical scrub, only 7.5% of the 5-minute group and 8.3% of the 10-minute group had a measurable CFU count of greater than or equal to 1, and colony counts were low in both groups (5- minute group: mean, 1.5 CFU; 10-minute group: mean, 2.0 CFU). There was no significant difference in CFUs following a 5- or 10-minute scrub (P = 0.28). CONCLUSIONS: The addition of a surgical skin scrub leads to a fourfold reduction in the skin CFU count compared with Betadine painting. However, there is no difference between the antibacterial effects of a 5- and 10-minute scrub. A 5-minute scrub may be sufficient in urologic prosthetic surgery.

The Hospital Water Environment as a Reservoir for Carbapenem-Resistant Organisms Causing Hospital-Acquired Infections-A Systematic Review of the Literature.

Over the last 20 years there have been 32 reports of carbapenem-resistant organisms in the hospital water environment, with half of these occurring since 2010. The majority of these reports have described associated clinical outbreaks in the intensive care setting, affecting the critically ill and the immunocompromised. Drains, sinks, and faucets were most frequently colonized, and Pseudomonas aeruginosa the predominant organism. Imipenemase (IMP), Klebsiella pneumoniae carbapenemase (KPC), and Verona integron-encoded metallo-ß-lactamase (VIM) were the most common carbapenemases found. Molecular typing was performed in almost all studies, with pulse field gel electrophoresis being most commonly used. Seventy-two percent of studies reported controlling outbreaks, of which just more than one-third eliminated the organism from the water environment. A combination of interventions seems to be most successful, including reinforcement of general infection control measures, alongside chemical disinfection. The most appropriate disinfection method remains unclear, however, and it is likely that replacement of colonized water reservoirs may be required for long-term clearance.

The Not-So-Good Prognosis of Streptococcal Periprosthetic Joint Infection Managed by Implant Retention: The Results of a Large Multicenter Study.

BACKGROUND.: Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success. METHODS.: A retrospective, observational, multicenter, international study was performed during 2003-2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy. RESULTS.: Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using ß-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%-46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with ß-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34). CONCLUSIONS.: This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of ß-lactams are confirmed and maybe also a potential benefit from adding rifampin.

Efficacy of ß-Lactam/ß-Lactamase Inhibitor Combinations for the Treatment of Bloodstream Infection Due to Extended-Spectrum-ß-Lactamase-Producing Enterobacteriaceae in Hematological Patients with Neutropenia.

ß-Lactam/ß-lactamase inhibitors (BLBLIs) were compared to carbapenems in two cohorts of hematological neutropenic patients with extended-spectrum-ß-lactamase (ESBL) bloodstream infection (BSI): the empirical therapy cohort (174 patients) and the definitive therapy cohort (251 patients). The 30-day case fatality rates and other secondary outcomes were similar in the two therapy groups of the two cohorts and also in the propensity-matched cohorts. BLBLIs might be carbapenem-sparing alternatives for the treatment of BSI due to ESBLs in these patients.

Healthcare-acquired infections: prevention strategies.

Healthcare-acquired infections (HAI) impact on patient care and have cost implications for the Australian healthcare system. The management of HAI is exacerbated by rising rates of antimicrobial resistance (AMR). Health-care workers and a contaminated hospital environment are increasingly implicated in the transmission and persistence of multi-resistant organisms (MRO), as well as other pathogens, such as Clostridium difficile. This has resulted in a timely focus on a range of HAI prevention actions. Core components include antimicrobial stewardship, to reduce overuse and ensure evidence-based antimicrobial use; infection prevention strategies, to control MRO - particularly methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE) and, more recently, multi-resistant Gram-negative bacteria; enhanced institutional investment in hand hygiene; hospital cleaning and disinfection; and the development of prescribing guidelines and standards of care. AMR surveillance and comparisons of prescribing are useful feedback activities once effectively communicated to end users. Successful implementation of these strategies requires cultural shifts at local hospital level and, to tackle the serious threat posed by AMR, greater co-ordination at a national level. HAI prevention needs to be multi-modal, requires broad healthcare collaboration, and the strong support and accountability of all medical staff.

Aggregatibacter aphrophilus Sacroiliitis Following Gastroscopy in a Young Sportsman.

We report a case of Aggregatibacter aphrophilus sacroiliitis in a young sportsman, presenting 48 hours after endoscopy and biopsy. Microbiological diagnosis was made only after repeated attempt at joint aspiration. The patient was cured after radiologically guided drainage and a prolonged course of directed antibiotics.

Prosthetic Valve Infective Endocarditis With Mycobacterium Fortuitum: Antibiotics Alone Can Be Curative.

Rapidly growing non-tuberculous mycobacteria (RGM) are a rare, often fatal cause of infective endocarditis. Although surgery has been the cornerstone of RGM endocarditis therapy, we present the first documented adult case of Mycobacterium fortuitum endocarditis cured with antibiotic therapy.

Problematic Dichotomization of Risk for Intensive Care Unit (ICU)-Acquired Invasive Candidiasis: Results Using a Risk-Predictive Model to Categorize 3 Levels of Risk From a Multicenter Prospective Cohort of Australian ICU Patients.

BACKGROUND: Delayed antifungal therapy for invasive candidiasis (IC) contributes to poor outcomes. Predictive risk models may allow targeted antifungal prophylaxis to those at greatest risk. METHODS: A prospective cohort study of 6685 consecutive nonneutropenic patients admitted to 7 Australian intensive care units (ICUs) for ≥72 hours was performed. Clinical risk factors for IC occurring prior to and following ICU admission, colonization with Candida species on surveillance cultures from 3 sites assessed twice weekly, and the occurrence of IC ≥72 hours following ICU admission or ≤72 hours following ICU discharge were measured. From these parameters, a risk-predictive model for the development of ICU-acquired IC was then derived. RESULTS: Ninety-six patients (1.43%) developed ICU-acquired IC. A simple summation risk-predictive model using the 10 independently significant variables associated with IC demonstrated overall moderate accuracy (area under the receiver operating characteristic curve = 0.82). No single threshold score could categorize patients into clinically useful high- and low-risk groups. However, using 2 threshold scores, 3 patient cohorts could be identified: those at high risk (score ≥6, 4.8% of total cohort, positive predictive value [PPV] 11.7%), those at low risk (score ≤2, 43.1% of total cohort, PPV 0.24%), and those at intermediate risk (score 3-5, 52.1% of total cohort, PPV 1.46%). CONCLUSIONS: Dichotomization of ICU patients into high- and low-risk groups for IC risk is problematic. Categorizing patients into high-, intermediate-, and low-risk groups may more efficiently target early antifungal strategies and utilization of newer diagnostic tests.

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

The Australian Group on Antimicrobial Resistance performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2014 survey was the second year to focus on blood stream infections. During 2014, 5,798 Enterobacteriaceae species isolates were tested using commercial automated methods (Vitek 2, BioMérieux; Phoenix, BD) and results were analysed using the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (January 2015). Of the key resistances, non-susceptibility to the third-generation cephalosporin, ceftriaxone, was found in 9.0%/9.0% of Escherichia coli (CLSI/EUCAST criteria) and 7.8%/7.8% of Klebsiella pneumoniae, and 8.0%/8.0% K. oxytoca. Non-susceptibility rates to ciprofloxacin were 10.4%/11.6% for E. coli, 5.0%/7.7% for K. pneumoniae, 0.4%/0.4% for K. oxytoca, and 3.5%/6.5% in Enterobacter cloacae. Resistance rates to piperacillin-tazobactam were 3.2%/6.8%, 4.8%/7.2%, 11.1%/11.5%, and 19.0%/24.7% for the same 4 species respectively. Fourteen isolates were shown to harbour a carbapenemase gene, 7 blaIMP-4, 3 blaKPC-2, 3 blaVIM-1, 1 blaNDM-4, and 1 blaOXA-181-lke.

Candida colonization as a risk marker for invasive candidiasis in mixed medical-surgical intensive care units: development and evaluation of a simple, standard protocol.

Colonization with Candida species is an independent risk factor for invasive candidiasis (IC), but the minimum and most practicable parameters for prediction of IC have not been optimized. We evaluated Candida colonization in a prospective cohort of 6,015 nonneutropenic, critically ill patients. Throat, perineum, and urine were sampled 72 h post-intensive care unit (ICU) admission and twice weekly until discharge or death. Specimens were cultured onto chromogenic agar, and a subset underwent molecular characterization. Sixty-three (86%) patients who developed IC were colonized prior to infection; 61 (97%) tested positive within the first two time points. The median time from colonization to IC was 7 days (range, 0 to 35). Colonization at any site was predictive of IC, with the risk of infection highest for urine colonization (relative risk [RR]=2.25) but with the sensitivity highest (98%) for throat and/or perineum colonization. Colonization of ≥2 sites and heavy colonization of ≥1 site were significant independent risk factors for IC (RR=2.25 and RR=3.7, respectively), increasing specificity to 71% to 74% but decreasing sensitivity to 48% to 58%. Molecular testing would have prompted a resistance-driven decision to switch from fluconazole treatment in only 11% of patients infected with C. glabrata, based upon species-level identification alone. Positive predictive values (PPVs) were low (2% to 4%) and negative predictive values (NPVs) high (99% to 100%) regardless of which parameters were applied. In the Australian ICU setting, culture of throat and perineum within the first two time points after ICU admission captures 84% (61/73 patients) of subsequent IC cases. These optimized parameters, in combination with clinical risk factors, should strengthen development of a setting-specific risk-predictive model for IC.

Dictyostelium discoideum Dgat2 can substitute for the essential function of Dgat1 in triglyceride production but not in ether lipid synthesis.

Triacylglycerol (TAG), the common energy storage molecule, is formed from diacylglycerol and a coenzyme A-activated fatty acid by the action of an acyl coenzyme A:diacylglycerol acyltransferase (DGAT). In order to conduct this step, most organisms rely on more than one enzyme. The two main candidates in Dictyostelium discoideum are Dgat1 and Dgat2. We show, by creating single and double knockout mutants, that the endoplasmic reticulum (ER)-localized Dgat1 enzyme provides the predominant activity, whereas the lipid droplet constituent Dgat2 contributes less activity. This situation may be opposite from what is seen in mammalian cells. Dictyostelium Dgat2 is specialized for the synthesis of TAG, as is the mammalian enzyme. In contrast, mammalian DGAT1 is more promiscuous regarding its substrates, producing diacylglycerol, retinyl esters, and waxes in addition to TAG. The Dictyostelium Dgat1, however, produces TAG, wax esters, and, most interestingly, also neutral ether lipids, which represent a significant constituent of lipid droplets. Ether lipids had also been found in mammalian lipid droplets, but the role of DGAT1 in their synthesis was unknown. The ability to form TAG through either Dgat1 or Dgat2 activity is essential for Dictyostelium to grow on bacteria, its natural food substrate.

Molecular epidemiology of enterococcal bacteremia in Australia.

Enterococci are a major cause of health care-associated infections and account for approximately 10% of all bacteremias globally. The aim of this study was to determine the proportion of enterococcal bacteremia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterize the molecular epidemiology of the Enterococcus faecalis and Enterococcus faecium isolates. From 1 January to 31 December 2011, 1,079 unique episodes of bacteremia were investigated, of which 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). The majority of bacteremias were health care associated, and approximately one-third were polymicrobial. Ampicillin resistance was detected in 90.4% of E. faecium isolates but was not detected in E. faecalis isolates. Vancomycin nonsusceptibility was reported in 0.6% and 36.5% of E. faecalis and E. faecium isolates, respectively. Unlike Europe and the United States, where vancomycin resistance in E. faecium is predominately due to the acquisition of the vanA operon, 98.4% of E. faecium isolates harboring van genes carried the vanB operon, and 16.1% of the vanB E. faecium isolates had vancomycin MICs at or below the susceptible breakpoint of the CLSI. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis pulsotypes, >50% belonged to two pulsotypes that were isolated across Australia. E. faecium consisted of 73 pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium isolates were identified as CC17 clones, of which approximately half were characterized as ST203, which was isolated Australia-wide. In conclusion, the Australian Enterococcal Sepsis Outcome Programme (AESOP) study has shown that although they are polyclonal, enterococcal bacteremias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.

Skin and soft tissue infections caused by nontuberculous mycobacteria.

PURPOSE OF REVIEW: Skin and soft tissues infections (SSTIs) caused by nontuberculous mycobacteria (NTM) are underrecognized and difficult to treat. Controversies exist for optimal medical management and the role of surgery. Defining the epidemiology in the environment, in animals and in healthcare aids disease prevention. This review focuses on recent advances in epidemiology, risk factors, diagnostics and therapy. RECENT FINDINGS: The increasing consumer appetite for cosmetic and body-modifying procedures (e.g. tattooing, mesotherapy, liposuction) has been associated with rises in sporadic cases and outbreaks of NTM SSTIs. In mainstream healthcare, recent epidemiological studies have helped to quantify the increased risk of NTM infection related to anti-tumour necrosis factor-α monoclonal antibody therapy. Cervicofacial lymphadenitis in children poses management dilemmas, but recent studies and resultant algorithms have simplified decision-making. Molecular studies have led to a better understanding of the epidemiology, therapy and course of Mycobacterium ulcerans infection (Buruli ulcer) that remains prevalent in many areas including sub-Saharan Africa and southeastern Australia. Apart from molecular methods, the widespread adoption of matrix-assisted laser desorption ionization-time of flight mass spectrometry by routine laboratories has potential to simplify and expedite the laboratory identification of NTMs. SUMMARY: An improved understanding of the epidemiology of NTM SSTIs indicates a need to apply effective infection control and ensure regulation of cosmetic and related procedures associated with nonsterile fluids. Broader access to newer diagnostic methods will continue to improve recognition of NTM disease. Along with a paucity of therapeutic agents, there is need for more reliable methods to assess susceptibility and selection of effective combination therapy.

Hospital-onset Gram-negative Surveillance Program annual report, 2011.

The Australian Group on Antimicrobial Resistance performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2011 survey focussed on hospital-onset infections, examining isolates from all specimens presumed to be causing disease. In 2011, 1,827 Escherichia coli, 537 Klebsiella species and 269 Enterobacter species were tested using a commercial automated method (Vitek 2, BioMérieux) and results were analysed using Clinical and Laboratory Standards Institute breakpoints from January 2012. Of the key resistances, non-susceptibilty to the third-generation cephalosporin, ceftriaxone, was found in 9.6% of E. coli and 9.5%-12.1% of Klebsiella spp. Non-susceptibility rates to ciprofloxacin were 10.6% for E. coli, 0.0%-8.3% for Klebsiella spp. and 0.0%-5.0% in Enterobacter spp. Resistance rates to gentamicin were 8.6%, 2.9%-10.9%, and 0.0%-15.6% for the same 3 groups respectively. Eight strains, 5 Klebsiella spp. and 3 Enterobacter spp. were shown to harbour a carbapenemase (IMP-4).

Community-onset Gram-negative Surveillance Program annual report, 2012.

The Australian Group on Antimicrobial Resistance performs regular period-prevalence studies to monitor changes in antimicrobial resistance in selected enteric Gram-negative pathogens. The 2012 survey focussed on community-onset infections, examining isolates from urinary tract infections from patients presenting to outpatient clinics, emergency departments or to community practitioners. In 2012, 2,025 Escherichia coli, 538 Klebsiella species and 239 Enterobacter species were tested using a commercial automated method (Vitek 2, BioMérieux) and results were analysed using Clinical and Laboratory Standards Institute breakpoints from January 2012. Of the key resistances, non-susceptibility to the third-generation cephalosporin, ceftriaxone, was found in 4.2% of E. coli and 4.6%-6.9% of Klebsiella spp. Non-susceptibility rates to ciprofloxacin were 6.9% for E. coli, 0.0%-3.5% for Klebsiella spp. and 0.8%-1.9% in Enterobacter spp, and resistance rates to piperacillin-tazobactam were 1.7%, 0.7%-9.2%, and 8.8%-11.4% for the same 3 groups respectively. Only 1 Enterobacter cloacae was shown to harbour a carbapenemase (IMP-4).