Development and piloting of a prevention assessment and response tool for healthcare-associated Staphylococcus aureus bloodstream infection (the SAB-PART Study) using a Delphi method.

BACKGROUND: Healthcare-associated Staphylococcus aureus bloodstream infection (HA-SAB) causes preventable harm in hospitalized patients. Currently, there is no standardized method available to review HA-SAB events in order to identify and target preventable risks requiring action at an organizational level. AIM: To develop a tool to classify SAB events, and the necessary response actions, according to the degree of preventability. METHODS: Following a literature review, a tool was developed. Consensus feedback and development of the tool was sought from experts (N = 11) in healthcare-associated infection surveillance using a Delphi technique. The completed tool was retrospectively applied to HA-SAB events (N = 43) that occurred at a large healthcare organization. FINDINGS: Survey completion rates were high (91-100%). Clinicians' poor adherence to infection prevention practices and lack of engagement with feedback processes was established as the key modifiable element. A second key theme was the need for structured and detailed response actions. This feedback was incorporated into the tool and refined until consensus on all elements was achieved. Pilot application of the tool found that 56% of HA-SAB events were highly or possibly preventable; modifiable factors for HA-SAB prevention were not present in the remainder of cases. CONCLUSION: A prevention assessment and response tool was successfully developed via a consensus method to assist organizations in investigating and responding to individual cases of HA-SAB and identify future priority areas for SAB reduction strategies. Wider use of the tool with routine surveillance activities is required to evaluate impact upon infection prevention programmes and patient outcomes.

Neurosyphilis: Concordance between cerebrospinal fluid analysis and subsequent antibiotic strategy for patients undergoing evaluation of a diagnosis of neurosyphilis.

INTRODUCTION: The confirmation or analysis and exclusion of a diagnosis of neurosyphilis has long presented a challenge for infectious diseases clinicians. The authors reviewed the concordance between cerebrospinal fluid (CSF) analysis and the subsequent antibiotic strategy for patients undergoing evaluation of a diagnosis of neurosyphilis. METHODS: All patients with positive serum syphilis serology referred for CSF analysis between January 2009 and May 2016 were included. Indications for CSF analysis were determined by review of the hospital electronic medical records. CSF parameters were determined from the hospital pathology database. Cases were defined as either 'confirmed', 'supportive' of, or 'not supportive' of a diagnosis of neurosyphilis based on existing definitions. Subsequent therapy was defined as for neurosyphilis, late latent primary syphilis or no therapy based on existing guidelines. RESULTS: Of 131 patients reviewed, 95.4% were male and HIV co-infected (74%). A confirmed diagnosis of neurosyphilis was met by fourteen patients (10.7%). All but two of these were treated with a neurosyphilis-directed regimen. Of the 58 patients treated with neurosyphilis antibiotics, 17.2% had no CSF findings suggestive of the diagnosis. Seventy-three patients were not treated for neurosyphilis; however 35 of these met the CSF criteria for a diagnosis supportive of neurosyphilis. CONCLUSIONS: The results of routine CSF analysis in patients with a possible diagnosis of neurosyphilis are inconsistently applied in the clinical setting, calling into question the value of routine CSF. Empirical neurosyphilis treatment should be considered up front in patients with high pre-test probability of the diagnosis.

Mobile phones and computer keyboards: unlikely reservoirs of multidrug-resistant organisms in the tertiary intensive care unit.

Few studies have used molecular epidemiological methods to study transmission links to clinical isolates in intensive care units. Ninety-four multidrug-resistant organisms (MDROs) cultured from routine specimens from intensive care unit (ICU) patients over 13 weeks were stored (11 meticillin-resistant Staphylococcus aureus (MRSA), two vancomycin-resistant enterococci and 81 Gram-negative bacteria). Medical staff personal mobile phones, departmental phones, and ICU keyboards were swabbed and cultured for MDROs; MRSA was isolated from two phones. Environmental and patient isolates of the same genus were selected for whole genome sequencing. On whole genome sequencing, the mobile phone isolates had a pairwise single nucleotide polymorphism (SNP) distance of 183. However, >15,000 core genome SNPs separated the mobile phone and clinical isolates. In a low-endemic setting, mobile phones and keyboards appear unlikely to contribute to hospital-acquired MDROs.

Overwhelming post-splenectomy sepsis in patients with asplenia and hyposplenia: a retrospective cohort study.

Overwhelming post-splenectomy infection (OPSI) is a serious complication of asplenia and is associated with encapsulated organisms, most commonly Streptococcus pneumoniae, but also Haemophilus influenzae and Neisseria meningitidis. We aimed to estimate the risk of infection in this patient group. We reviewed data collected by the Victorian Spleen Registry in Australia. On registration, all patients are asked about significant infections requiring admission to hospital for intravenous antibiotics; those requiring admission to ICU were defined as OPSI. In the 3274 asplenic patients registered 492 patients reported at least one episode of infection. There were 47 episodes of OPSI requiring intensive care (incidence rate 1·11/1000 patient-years). The risk of OPSI was highest in older patients, and there were no statistically significant differences in incidence by reason for splenectomy except for a higher rate in patients with medical hyposplenia. This study reinforces that post-splenectomy infection is a clinically significant but uncommon complication, and that fulminant infection requiring intensive care is a minority of all infections.

Mucormycete infection or colonisation: experience of an Australian tertiary referral centre.

Mucormycosis is associated with significant morbidity and mortality. We reviewed patients with mucormycete isolated at Alfred Health, Australia. A retrospective review of 66 patients with mucormycete(s) identified, between 1 April 2008 and 30 June 2014. Baseline demographic, microbiological, radiological, treatment/outcome data were recorded. Site of isolation was sinopulmonary in 77% and skin/soft tissue in 21%. A total of 32% of cases were proven-IFD, 12% probable-IFD and 56% were defined as no-IFD (or colonisation). Rhizopus spp. was identified in 48%. Comparing probable/proven-IFD with no-IFD/colonisation, more patients were postallogeneic stem cell transplantation (28% vs. 0%, P < 0.01) and were receiving immunosuppressive therapy (59% vs. 24%, P < 0.01) including prednisolone >20 mg daily (24% vs. 5%, P = 0.04). A total of 93% of patients with proven/probable IFD received treatment while 30% of no-IFD/colonisation were treated. A total of 72% of patients with proven/probable IFD and 92% of those with colonisation had no further mucormycete isolated. Thirty day mortality was higher in the proven/probable-IFD cohort (24%) compared with no-IFD/colonisation (3%) (P = 0.02). Mucormycosis remains uncommon, with 56% of cases not associated with clinical infection. Immunosuppressive therapy remains strongly associated with mucormycosis. Mortality remains high in those with proven/probable IFD.

Differing epidemiology of two major healthcare-associated meticillin-resistant Staphylococcus aureus clones.

BACKGROUND: Two meticillin-resistant Staphylococcus aureus (MRSA) clones, sequence type (ST) 22 and ST239, have successfully spread globally. Across Australia, ST22 has supplanted ST239 as the main healthcare-associated MRSA. To understand the reasons underlying this shift, the epidemiology and clinical features of infections due to ST22 and ST239 MRSA isolates from a tertiary hospital in Melbourne, Australia were compared. METHODS: Over six months, consecutive MRSA isolates with clinical data were collected from specimens referred to Alfred Health Pathology (AHP). Isolates were genotyped by a multi-locus-sequence-typing-based high-resolution melting method. FINDINGS: Three hundred and twenty-eight of 1079 (30%) S. aureus isolated by AHP were MRSA. Of these, 313 were genotyped; 78 (25%) were clonal complex (CC) 22 (representing ST22) and 142 (45%) were CC239 (representing ST239). Common clinical syndromes included skin or soft tissue, respiratory tract and osteo-articular infections. On multi-variate logistic regression, compared with CC239, CC22 was associated with older patients [adjusted odds ratio (aOR) 1.04 for each year increase, 95% confidence interval (CI) 1.02-1.07)], and patients from subacute hospitals (aOR 2.7, 95% CI 1.2-5.8) or long-term care facilities (LTCFs; aOR 5.5, 95% CI 2.0-14.5). Median time from patient admission to MRSA isolation was nine days for CC239 and one day for CC22 (P < 0.01). MRSA strain epidemiology varied according to hospital unit. CONCLUSIONS: CC22 and CC239 MRSA have differing ecological niches. CC22 is associated with elderly patients in LTCFs, and CC239 is associated with nosocomial acquisition. Infection control strategies involving LTCFs and their residents will likely be required to achieve continued MRSA control.

Clinical utility of panfungal polymerase chain reaction for the diagnosis of invasive fungal disease: a single center experience.

The role of panfungal polymerase chain reaction (PCR) assays for diagnosis of invasive fungal disease (IFD) is inadequately defined. We describe the use of an internal transcribed spacer 1 (ITS-1) region-directed panfungal PCR in this context at a tertiary referral transplant center. A retrospective review of patients at Alfred Health, Melbourne, Australia (2009-2014) who had clinical samples referred for panfungal PCR testing was conducted. Baseline patient characteristics, antifungal drug history, fungal culture/histopathology, and radiology results were recorded. For bronchoalveolar lavage (BAL) fluid samples, identification of a fungus other than a Candida spp. was defined as a potential pathogen.Of 138 panfungal PCR tests (108 patients), 41 (30%) were positive for a fungal product. Ninety-seven percent (134/138) of specimens were from immunocompromised hosts. Thirteen percent (19/138) of panfungal PCR positive results were for potential pathogens and potential pathogens were detected more frequently in tissue as compared with BAL (12/13 vs. 6/26; P = .0001). No positive panfungal PCR results were obtained from CSF specimens. If histopathology examination was negative, panfungal PCR identified a potential pathogen in only 12% (11/94) of specimens. For the 20 culture negative/histopathology positive specimens, diagnosis of IFD to causative species level by panfungal PCR occurred in 35% (6/20).Sterile site specimens, in particular tissue, were more frequently panfungal PCR positive for potential pathogens than BAL. The utility of panfungal PCR appears greatest in tissue specimens, as an adjunct to histopathology to improve diagnostic sensitivity and specificity. Based on the results of this study we are now only testing tissue specimens by panfungal PCR.

Reduced In Vitro Activity of Ceftaroline by Etest among Clonal Complex 239 Methicillin-Resistant Staphylococcus aureus Clinical Strains from Australia.

A total of 421 methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates were tested for ceftaroline susceptibility by Etest (bioMérieux). A multidrug resistant phenotype was found in 40.9%, and clonal complex 239 (CC239) was found in 33.5%. Ceftaroline nonsusceptibility (MIC, >1.0 µg/ml) was 16.9% overall. Nonsusceptibility was significantly higher in CC239 (41.1%, 58/141) and in isolates with a multidrug resistant phenotype (35.5%, 61/172) compared with comparators (P < 0.0001). Nonsusceptibility of common multidrug resistant MRSA clones limits the empirical use of ceftaroline for these infections.

Travel risk assessment, advice and vaccinations in immunocompromised travellers (HIV, solid organ transplant and haematopoeitic stem cell transplant recipients): A review.

International travellers with immunocompromising conditions such as human immunodeficiency virus (HIV) infection, solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT) are at a significant risk of travel-related illnesses from both communicable and non-communicable diseases, depending on the intensity of underlying immune dysfunction, travel destinations and activities. In addition, the choice of travel vaccinations, timing and protective antibody responses are also highly dependent on the underlying conditions and thus pose significant challenges to the health-care providers who are involved in pre-travel risk assessment. This review article provides a framework of understanding and approach to aforementioned groups of immunocompromised travellers regarding pre-travel risk assessment and management; in particular travel vaccinations, infectious and non-infectious disease risks and provision of condition-specific advice; to reduce travel-related mortality and morbidity.

Impact of vanB vancomycin-resistant enterococcal bacteraemia analysed as a time-varying covariate on length of hospital stay.

The impact of vanB vancomycin-resistant enterococci (VRE) bacteraemia on length of stay (LOS) in hospital, after adjusting for the time-varying nature of enterococcal bacteraemia (variable onset of bacteraemia post-admission), is unknown. Survival analyses (time-varying Cox and competing risks regression) were performed on vanB VRE bacteraemia patients, matched 1:1 with vancomycin-susceptible enterococci bacteraemia patients to determine the factors associated with LOS in these patients. In Cox regression analysis, vanB VRE bacteraemia, intensive-care-unit admission, Charlson co-morbidity index score ⩾4, and an increase in the time to receive appropriate antibiotics were associated with prolonged LOS. Competing risks regression which accounts for the influence of in-patient mortality on the ability to observe the event discharge alive from hospital suggests that, vanB VRE bacteraemia was not significantly associated with prolonged LOS. For the first time, the rate of discharge from hospital in patients with vanB VRE bacteraemia has been quantified.

Enterococcal bacteraemia: factors influencing mortality, length of stay and costs of hospitalization.

Enterococci are a major cause of nosocomial bacteraemia. The impacts of vanB vancomycin resistance and antibiotic therapy on outcomes in enterococcal bacteraemia are unclear. Factors that affect length of stay (LOS) and costs of managing patients with enterococcal bacteraemia are also unknown. This study aimed to identify factors associated with mortality, LOS and hospitalization costs in patients with enterococcal bacteraemia and the impact of vancomycin resistance and antibiotic therapy on these outcomes. Data from 116 patients with vancomycin-resistant Enterococci (VRE), matched 1:1 with patients with vancomycin-susceptible Enterococcus (VSE), from two Australian hospitals were reviewed for clinical and economic outcomes. Univariable and multivariable logistic and quantile regression analyses identified factors associated with mortality, LOS and costs. Intensive care unit admission (OR, 8.57; 95% CI, 3.99-18.38), a higher burden of co-morbidities (OR, 4.55; 95% CI, 1.83-11.33) and longer time to appropriate antibiotics (OR, 1.02; 95% CI, 1.01-1.03) were significantly associated with mortality in enterococcal bacteraemia. VanB vancomycin resistance increased LOS (4.89 days; 95% CI, 0.56-11.52) and hospitalization costs (AU$ 28 872; 95% CI, 734-70 667), after adjustment for confounders. Notably, linezolid definitive therapy was associated with lower mortality (OR, 0.13; 95% CI, 0.03-0.58) in vanB VRE bacteraemia patients. In patients with VSE bacteraemia, time to appropriate antibiotics independently influenced mortality, LOS and hospitalization costs, and underlying co-morbidities were associated with mortality. The study findings highlight the importance of preventing VRE bacteraemia and the significance of time to appropriate antibiotics in the management of enterococcal bacteraemia.

Differing risk factors for vancomycin-resistant and vancomycin-sensitive enterococcal bacteraemia.

Enterococcus is an important cause of bacteraemia. Previous epidemiological studies examining risk factors for enterococcal bacteraemia have used traditional case-control study designs, which can be potentially biased. This case-case-control study examining risk factors for enterococcal bacteraemia was conducted over 10 years (January 2000 to December 2009) in a tertiary, university-affiliated hospital. There were 440 episodes of enterococcal bacteraemia, 80 of which were caused by vancomycin-resistant Enterococcus (VRE). Two multivariable models were generated, comparing VRE and vancomycin-susceptible Enterococcus (VSE) with the same control group. VRE bacteraemia was associated with central venous catheter use (OR 11.6, 95% CI 2.6-51.5), neutropenia (OR 16.9, 95% CI 2.4-120.2), and allogenic bone marrow transplantation (OR 18.0, 95% CI 2.4-133.4). In contrast, VSE bacteraemia risk factors included: age (OR 1.0, 95% CI 1.0-1.1), exposure to metronidazole (OR 8.7, 95% CI 1.7-43.5), and gastrointestinal disease (OR 6.4, 95% CI 1.2-34.5). Meropenem use decreased the risk of VSE bacteraemia (OR 0.3, 95% CI 0.1-0.9). Hypoalbuminaemia was the only factor identified in both models (VRE, OR 6.0, 95% CI 1.7-21.1; VSE, OR 3.3, 95% CI 1.4-7.7). The absence of substantial overlap of risk factors for VRE and VSE argues in favour of differences in pathogenesis. These data suggest that environmental sources are more important in VRE bacteraemia. Endogenous sources, particularly the gastrointestinal tract, play a pivotal role in VSE bacteraemia. This study highlights the importance of infection control protocols to reduce the risk of VRE bacteraemia.

Plasmodium species co-infection as a cause of treatment failure.

We report a case of Plasmodium falciparum and Plasmodium malariae coinfection with associated failure of clinical response to artemether + lumefantrine therapy. This case highlights the need to consider co-infection in the setting of apparent treatment failure and the impact of mixed species infection upon host dynamics and clinical presentation. Recognition of malarial co-infection is clinically important for determining appropriate therapy and preventing disease sequelae.

Candida infective endocarditis.

Candida infective endocarditis (IE) is uncommon but often fatal. Most epidemiologic data are derived from small case series or case reports. This study was conducted to explore the epidemiology, treatment patterns, and outcomes of patients with Candida IE. We compared 33 Candida IE cases to 2,716 patients with non-fungal IE in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS). Patients were enrolled and the data collected from June 2000 until August 2005. We noted that patients with Candida IE were more likely to have prosthetic valves (p < 0.001), short-term indwelling catheters (p < 0.0001), and have healthcare-associated infections (p < 0.001). The reasons for surgery differed between the two groups: myocardial abscess (46.7% vs. 22.2%, p = 0.026) and persistent positive blood cultures (33.3% vs. 9.9%, p = 0.003) were more common among those with Candida IE. Mortality at discharge was higher in patients with Candida IE (30.3%) when compared to non-fungal cases (17%, p = 0.046). Among Candida patients, mortality was similar in patients who received combination surgical and antifungal therapy versus antifungal therapy alone (33.3% vs. 27.8%, p = 0.26). New antifungal drugs, particularly echinocandins, were used frequently. These multi-center data suggest distinct epidemiologic features of Candida IE when compared to non-fungal cases. Indications for surgical intervention are different and mortality is increased. Newer antifungal treatment options are increasingly used. Large, multi-center studies are needed to help better define Candida IE.

Guidelines for the prevention of sepsis in asplenic and hyposplenic patients.

Asplenic or hyposplenic patients are at risk of fulminant sepsis. This entity has a mortality of up to 50%. The spectrum of causative organisms is evolving as are recommended preventive strategies, which include education, prophylactic and standby antibiotics, preventive immunizations, optimal antimalarial advice when visiting endemic countries and early management of animal bites. However, there is evidence that adherence to these strategies is poor. Consensus-updated guidelines have been developed to help Australian and New Zealand clinicians and patients in the prevention of sepsis in asplenic and hyposplenic patients.

In vitro activities of 'new' and 'conventional' antibiotics against multi-drug resistant Gram negative bacteria from patients in the intensive care unit.

OBJECTIVES: To identify and collect clinical isolates of multi-drug resistant Gram negative bacteria and to perform antimicrobial susceptibility testing using an extended panel of antibiotics including tigecycline, colistin, aztreonam, piperacillin/tazobactam and ampicillin/sulbactam. METHODS: Minimum inhibitory concentrations (MICs) using the Epsilometer test (E-test) methodology were determined for 28 distinct multi-drug resistant Gram negative isolates from patients in the intensive care unit (ICU). RESULTS: Tigecycline had good in vitro activity against Acinetobacter species and Enterobacter cloacae, and colistin had potent in vitro activity against Acinetobacter, E. cloacae and Pseudomonas aeruginosa. Enterobacter cloacae and Serratia marcescens but not P. aeruginosa or Acinetobacter species were susceptible to piperacillin/tazobactam. Ampicillin/sulbactam had poor in vitro activity for most isolates tested. The activity of tigecycline and colistin did not appear to be affected by the presence of extended spectrum beta-lactamases (ESBLs) and metallo-beta-lactamases (MBLs) and aztreonam maintained its in vitro activity against the Enterobacteriaceae tested despite the presence of MBLs. CONCLUSIONS: Tigecycline and colistin have potent in vitro activity and might have useful therapeutic activity in patients with infections due to multi-drug resistant Acinetobacter species and E. cloacae, including those harbouring ESBLs and MBLs. In addition, colistin demonstrated potent in vitro activity against multi-drug resistant P. aeruginosa.

A longitudinal study of Acinetobacter in three Australian hospitals.

Acinetobacter has recently risen in prominence as a nosocomial pathogen, particularly due to increasing antibiotic resistance. The aim of this study was to describe changes in rates and antibiotic susceptibility patterns of Acinetobacter in three Melbourne hospitals. This was a retrospective review of microbiology records over five years. The rates of new clinical isolates of Acinetobacter per 10 000 discharges per quarter were calculated. Other information collected included antibiotic susceptibility patterns, age, gender, length of stay and ward [intensive care unit (ICU) or non-ICU]. Rates increased substantially at two hospitals, but not at the third. Increasing numbers at one hospital were associated with antibiotic resistance. Most first isolates were identified while the patient was in the ICU. Many isolates were from respiratory specimens, although a significant proportion was from blood. This study documents the establishment of Acinetobacter as a nosocomial pathogen in two Melbourne hospitals and serves as a warning for the future.

Strongyloides stercoralis: risks posed to immigrant patients in an Australian tertiary referral centre.

BACKGROUND: Strongyloides stercoralis is a nematode human parasite with a global prevalence that is able to maintain a prolonged infestation by means of its autoinfective life cycle. Immunosuppression may result in a life-threatening hyperinfection syndrome. Recent changes in migration have resulted in the arrival of many immigrants from endemic areas. As to whether physicians are alert to the risks of strongyloidiasis in these patient groups is unclear. The aim of the study was to assess the risks posed by chronic strongyloidiasis in patients presenting to a tertiary referral centre and the need for screening of immigrant patients before immunosuppression. METHODS: The study comprised a retrospective review of cases of strongyloidiasis presenting to the Alfred Hospital, Melbourne. Thirty-three cases were diagnosed by either positive serology or faecal microscopy between January 1998 and January 2005. The medical records for 29 cases were examined with regard to demographics, clinical features and complications. RESULTS: Two major groups were identified: immigrants (17) and returned travellers (11). Six immigrants, but no returned traveller, developed a hyperinfective syndrome. Five immigrants received immunosuppressive therapies before developing symptoms of hyperinfection and this was complicated by life-threatening sepsis in two patients. Diagnosis was frequently delayed in the immigrant group who were significantly more likely to present with respiratory symptoms. Four immigrants and two returned travellers were treated with corticosteroids for symptoms that were probably related to larval migration. CONCLUSION: Before giving immunosuppressive therapies, patients with a history of potential exposure must be investigated for strongyloidiasis and consideration given to empirical treatment.

Rate of nosocomial transmission of vancomycin-resistant enterococci from isolated patients.

To evaluate an isolation policy for patients colonised with vancomycin-resistant enterococci (VRE), we instituted active surveillance for transmission to uncolonised patients. Surveillance rectal swabs were taken and pulsed-field gel electrophoresis was performed on positive isolates. VRE transmission with an identical genotype occurred in 5 patients, giving a transmission rate of 3.7 per 1000 patient days, or 1 patient per ward each week. The present study provides a baseline for -assessment of VRE transmission and will be useful in evaluation of the effectiveness of infection control interventions.

Risk factors for acquisition of methicillin-resistant Staphylococcus aureus (MRSA) by trauma patients in the intensive care unit.

In a previous study in the intensive care unit (ICU) of the Alfred Hospital, Melbourne, Australia, it was demonstrated that trauma patients were at particular risk of becoming colonized by methicillin-resistant Staphylococcus aureus (MRSA). We examined risk factors for MRSA acquisition in these patients using a cohort study comparing the 31 patients who acquired MRSA with 65 who did not. Data collected included ICU length of stay (LOS), mechanism of trauma, site of injury, type of surgery, trauma severity and antibiotic usage. Odds ratios (OR) were determined and adjusted for LOS. LOS in the ICU was a significant univariate predictor of MRSA acquisition (OR 13.7). When adjusted for LOS, mechanism of trauma (OR 10.4), laparotomy (OR 6.3) and administration of ticarcillin/clavulanic acid (OR 4.5) or glycopeptides (OR 5.9) remained significant. We confirmed our previous finding that LOS was associated with MRSA acquisition. Receipt of antibiotics correlated with reported literature. Novel associations were road trauma as a mechanism and laparotomy.