The impact of 10-valent pneumococcal vaccine introduction on invasive disease in Fiji.

BACKGROUND: In 2012, Fiji introduced the 10-valent pneumococcal conjugate vaccine (PCV10). We assessed the impact of PCV10 on invasive pneumococcal disease (IPD), probable bacterial or pneumococcal meningitis (PBPM), meningitis and sepsis 3-5 years post-introduction. METHODS: Laboratory-confirmed IPD and PBPM cases were extracted from national laboratory records. ICD-10-AM coded all-cause meningitis and sepsis cases were extracted from national hospitalisation records. Incidence rate ratios were used to compare outcomes pre/post-PCV10, stratified by age groups: 1-23m, 2-4y, 5-9y, 10-19y, 20-54y, ≥55y. To account for different detection and serotyping methods in the pre-and post-PCV10 period, a Bayesian inference model estimated serotype-specific changes in IPD, using pneumococcal carriage and surveillance data. FINDINGS: There were 423 IPD, 1,029 PBPM, 1,391 all-cause meningitis and 7,611 all-cause sepsis cases. Five years post-PCV10 introduction, IPD declined by 60% (95%CI: 37%, 76%) in children 1-23m months old, and in age groups 2-4y, 5-9y, 10-19y although confidence intervals spanned zero. PBPM declined by 36% (95%CI: 21%, 48%) among children 1-23 months old, and in all other age groups, although some confidence intervals spanned zero. Among children <5y of age, PCV10-type IPD declined by 83% (95%CI; 70%, 90%) and with no evidence of change in non-PCV10-type IPD (9%, 95%CI; -69, 43%). There was no change in all-cause meningitis or sepsis. Post-PCV10, the most common serotypes in vaccine age-eligible and non-age eligible people were serotypes 8 and 23B, and 3 and 7F, respectively. INTERPRETATIONS: Our study demonstrates the effectiveness of PCV10 against IPD in a country in the Asia-Pacific of which there is a paucity of data. FUNDING: This study was support by the Department of Foreign Affairs and Trade of the Australian Government and Fiji Health Sector Support Program (FHSSP). FHSSP is implemented by Abt JTA on behalf of the Australian Government.

Longitudinal evaluation of laboratory-based serological assays for SARS-CoV-2 antibody detection.

Serological assays for SARS-CoV-2 infection are now widely available for use in diagnostic laboratories. Limited data are available on the performance characteristics in different settings, and at time periods remote from the initial infection. Validation of the Abbott (Architect SARS-CoV-2 IgG), DiaSorin (Liaison SARS-CoV-2 S1/S2 IgG) and Roche (Cobas Elecsys Anti-SARS-CoV-2) assays was undertaken utilising 217 serum samples from 131 participants up to 7 months following COVID-19 infection. The Abbott and DiaSorin assays were implemented into routine laboratory workflow, with outcomes reported for 2764 clinical specimens. Sensitivity and specificity were concordant with the range reported by the manufacturers for all assays. Sensitivity across the convalescent period was highest for the Roche at 95.2-100% (95% CI 81.0-100%), then the DiaSorin at 88.1-100% (95% CI 76.0-100%), followed by the Abbott 68.2-100% (95% CI 53.4-100%). Sensitivity of the Abbott assay fell from approximately 5 months; on this assay paired serum samples for 45 participants showed a significant drop in the signal-to-cut-off ratio and 10 sero-reversion events. When used in clinical practice, all samples testing positive by both DiaSorin and Abbott assays were confirmed as true positive results. In this low prevalence setting, despite high laboratory specificity, the positive predictive value of a single positive assay was low. Comprehensive validation of serological assays is necessary to determine the optimal assay for each diagnostic setting. In this low prevalence setting we found implementation of two assays with different antibody targets maximised sensitivity and specificity, with confirmatory testing necessary for any sample which was positive in only one assay.

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.

Vancomycin-intermediate Staphylococcus aureus isolates are attenuated for virulence when compared with susceptible progenitors.

OBJECTIVES: Vancomycin-intermediate Staphylococcus aureus (VISA) is associated with genetic changes that may also impact upon pathogenicity. In the current study, we compared the virulence of clinical VISA strains with their isogenic vancomycin-susceptible progenitors (VSSA). METHODS: Production of the critical virulence protein, α toxin, was assessed using Western blot analysis and was correlated to agr activity using a bioluminescent agr-reporter. Cytotoxicity and intracellular persistence were compared ex vivo for VSSA and VISA within non-professional phagocytes (NPP). Virulence and host immune responses were further explored in vivo using a murine model of bacteraemia. RESULTS: VISA isolates produced up to 20-fold less α toxin compared with VSSA, and this was corroborated by either loss of agr activity due to agr mutation, or altered agr activity in the absence of mutation. VISA were less cytotoxic towards NPP and were associated with enhanced intracellular persistence, suggesting that NPP may act as a reservoir for VISA. Infection with VSSA strains produced higher mortality in a murine bacteraemia model (≥90% 7-day mortality) compared with infection with VISA isolates (20% to 50%, p <0.001). Mice infected with VISA produced a dampened immune response (4.6-fold reduction in interleukin-6, p <0.001) and persistent organ bacterial growth was observed for VISA strains out to 7 days. CONCLUSIONS: These findings highlight the remarkable adaptability of S. aureus, whereby, in addition to having reduced antibiotic susceptibility, VISA alter the expression of pathogenic factors to circumvent the host immune response to favour persistent infection over acute virulence.

Asymptomatic and symptomatic urethral gonorrhoea in men who have sex with men attending a sexual health service.

OBJECTIVES: Guidelines regarding whether men who have sex with men (MSM) without symptoms of urethritis should be screened for urethral gonorrhoea differ between countries. We examined the rate of asymptomatic urethral gonorrhoea in MSM using sensitive nucleic acid amplification testing. METHODS: This study was conducted on consecutive MSM attending the Melbourne Sexual Health Centre between July 2015 and May 2016 for sexually transmitted infections screening. Gonorrhoea testing with the Aptima Combo 2 (AC2) assay was performed on all urine specimens obtained from MSM, whether symptoms of urethritis were present or not. Men were classified as having: typical discharge if they reported symptoms suggesting purulent discharge; other symptoms if they reported other symptoms of urethritis; and no symptoms if they reported no urethral symptoms. RESULTS: During the study period, there were 7941 clinic visits by 5947 individual MSM with 7090 urine specimens obtained from 5497 individual MSM tested with the AC2 assay. Urethral gonorrhoea was detected in 242 urine specimens from 228 individual MSM. The majority (189/242, 78%, 95% CI 73-83) reported typical discharge, 27/242 (11%, 95% CI 8-16) reported other urethral symptoms, and 26/242 (11%, 95% CI 7-15) reported no symptoms on the day of presentation and testing. Among men with urethral gonorrhoea, the proportions with concurrent pharyngeal or rectal gonorrhoea were 32% (134/210) and 64% (74/235), respectively. The mean interval between last reported sexual contact and onset of typical urethral discharge, where present, was 3.9 days. CONCLUSION: The findings from our study lend support to guidelines that recommend screening asymptomatic MSM for urethral gonorrhoea.

A large outbreak of Campylobacter jejuni infection in a university college caused by chicken liver pâté, Australia, 2013.

In October 2013, public health authorities were notified of a suspected outbreak of gastroenteritis in students and guests following a catered function at a university residential college. A retrospective cohort study was undertaken to examine whether foods served at the function caused illness. A total of 56 cases of gastroenteritis, including seven laboratory-confirmed cases of Campylobacter jejuni infection, were identified in 235 eligible respondents. Univariate analysis showed a significant association with a chicken liver pâté entrée [relative risk (RR) 3·64, 95% confidence interval (CI) 2·03-6·52, P < 0·001], which retained significance after adjustment for confounding via multivariable analysis (adjusted RR 2·80, 95% CI 1·26-6·19, P = 0·01). C. jejuni and C. coli were also isolated in chicken liver pâté recovered from the college's kitchen. Subsequent whole genome multilocus sequence typing (wgMLST) of clinical and food-derived C. jejuni isolates showed three genetically distinct sequence types (STs) comprising ST528, ST535 (both clinically derived) and ST991 (food derived). The study demonstrates the value of utilizing complementary sources of evidence, including genomic data, to support public health investigations. The use of wgMLST highlights the potential for significant C. jejuni diversity in epidemiologically related human and food isolates recovered during outbreaks linked to poultry liver.

Managing a nosocomial outbreak of carbapenem-resistant Klebsiella pneumoniae: an early Australian hospital experience.

BACKGROUND: Carbapenems are traditionally reserved as the last line of defence for treatment of serious infections with multiresistant Gram-negative bacilli. Reports of Klebsiella pneumoniae carbapenemase (KPC)-producing organisms have been emerging globally, but rare in Australasia to date. We describe an outbreak of KPC-2 producing K. pneumoniae at an Australian hospital. METHODS: After initial detection in October 2012, a retrospective review of patients with meropenem-resistant K. pneumoniae to June 2012, and ongoing prospective surveillance, was undertaken. Included patients were admitted to the hospital after June 2012 and had meropenem-resistant K. pneumoniae isolated from any site. Available isolates underwent detection of the KPC-2 gene by polymerase chain reaction and molecular typing was performed to determine genetic relatedness between isolates. Point-prevalence screening was performed on selected wards to detect asymptomatic carriage. Infection control procedures were implemented to contain the outbreak. RESULTS: Ten cases were identified in the initial cluster. Eight were localised to a single inpatient ward. Point-prevalence screening revealed one extra case. After temporary containment, re-emergence of KPC-producing isolates was observed post October 2013 with 18 further cases identified. Four K. pneumoniae isolates in the 2012 cluster and 16 from the 2013-2014 cluster were referred for further testing. All carried the KPC-2 beta-lactamase gene. The 2012 isolates were genetically similar to the 2014 isolates. CONCLUSION: KPC-2 mediated resistance is an emerging threat in Australia. The re-emergence of KPC despite initial containment emphasises the need for constant vigilance in the microbiology laboratory and ongoing maintenance of infection control and antimicrobial stewardship activity.

Effects of vapocoolant spray on skin sterility prior to intravenous cannulation.

BACKGROUND: Alkane vapocoolant sprays evaporate rapidly, lower skin temperature and result in a temporary interruption in pain sensation. They reduce the pain of intravenous cannulation. However, concern exists that they may recontaminate the sterile cannulation site. AIM: To determine the effects of vapocoolant spray on skin sterility prior to cannulation. METHODS: Fifty patients from the emergency department of a large tertiary metropolitan hospital were enrolled in this study. Bacterial skin swabs were taken from the dorsum of both hands of each patient. From one hand, a swab was taken following standard chlorhexidine disinfection, and a second swab was taken following the application of vapocoolant spray. From the other hand, a swab was taken from unprepared (non-disinfected) skin, and a second swab was taken following vapocoolant application. Skin swabs were sent for microbiological culture and quantitative comparison. FINDINGS: The administration of vapocoolant after skin disinfection did not increase the bacterial colony count significantly: median 0.0 [interquartile range (IQR) 0.0] vs 0.0 (IQR 0.0) (P = 0.71). The administration of vapocoolant to the unprepared skin decreased the colony count significantly: median 33.5 (IQR 68) vs 3.0 (IQR 11) (P < 0.001). CONCLUSION: Alkane vapocoolant spray does not recontaminate the skin after disinfection, and should pose no increased risk of infection when used as an anaesthetic agent prior to intravenous cannulation following disinfection. While it does have inherent bactericidal activity, this is not sufficient for it to be used as the sole disinfectant.

Whole genome sequencing in clinical and public health microbiology.

Genomics and whole genome sequencing (WGS) have the capacity to greatly enhance knowledge and understanding of infectious diseases and clinical microbiology.The growth and availability of bench-top WGS analysers has facilitated the feasibility of genomics in clinical and public health microbiology.Given current resource and infrastructure limitations, WGS is most applicable to use in public health laboratories, reference laboratories, and hospital infection control-affiliated laboratories.As WGS represents the pinnacle for strain characterisation and epidemiological analyses, it is likely to replace traditional typing methods, resistance gene detection and other sequence-based investigations (e.g., 16S rDNA PCR) in the near future.Although genomic technologies are rapidly evolving, widespread implementation in clinical and public health microbiology laboratories is limited by the need for effective semi-automated pipelines, standardised quality control and data interpretation, bioinformatics expertise, and infrastructure.

The epidemiology of sepsis during rapid response team reviews in a teaching hospital.

In a three-month retrospective study, we assessed the proportion of rapid response team (RRT) calls associated with systemic inflammatory response syndrome (SIRS) and sepsis. We also documented the site of infection (whether it was community- or hospital-acquired), antibiotic modifications after the call and in-hospital outcomes. Amongst 358 RRT calls, two or more SIRS criteria were present in 277 (77.4%). Amongst the 277 RRT calls with SIRS criteria, 159 (57.4%) fulfilled sepsis criteria in the 24 hours before and 12 hours after the call. There were 118 of 277 (42.6%) calls with SIRS criteria but no evidence of sepsis and 62 of 277 (22.3%) calls associated with both criteria for sepsis as well as an alternative cause for SIRS. Hence, 159 (44.4%) of all 358 RRT calls over the three-month study period fulfilled criteria for sepsis and in 97 (159-62) (27.1%) of the 358 calls, there were criteria for sepsis without other causes for SIRS criteria. The most common sites of infection were respiratory tract (86), abdominal cavity (38), urinary tract (26) and bloodstream (26). Infection was hospital-acquired in 91 (57.2%) and community-acquired in 67 (42.1%) cases, respectively. Patients were on antibiotics in 127 of 159 (79.9%) cases before the RRT call and antibiotics were added or modified in 76 of 159 (47.8%) cases after RRT review. The hospital length-of-stay of patients who received an RRT call associated with sepsis was longer than those who did not (16.0 [8.0 to 28.5] versus 10 days [6.0 to 18.0]; P=0.002).

The epidemiology of bacteriuria and candiduria in critically ill patients.

An observational study was conducted to describe the epidemiology of bacteriuria and candiduria in the intensive care unit (ICU), and the occurrence of blood stream infection (BSI) associated with ICU-acquired positive urine culture. Between 2006 and 2011, 444 episodes of either bacteriuria or candiduria defined by positive urine culture (microorganisms ⩾105 c.f.u./ml) occurred in 406 patients. Three hundred and seventy-seven (85%) were hospital-acquired including 221 which were ICU-acquired (6·4 ± 0·8 episodes/1000 ICU days). Escherichia coli was the most common bacteria of both community- and ICU-acquired bacteriuria/candiduria (49·2% and 29%, respectively). Candida spp. represented 55% (129/236) of pathogens responsible for ICU-acquired positive urine cultures. Patients with ICU-acquired candiduria had greater illness severity at ICU admission than those with ICU-acquired bacteriuria (APACHE III score 79 ± 25 vs. 66 ± 31, P = 0·0015). BSI associated with ICU-acquired positive urine culture occurred in 0·15/1000 ICU days and was more often due to Candida. In this study, Candida was the most common pathogen responsible for ICU-acquired positive urine cultures and illness severity was a risk factor for candiduria in the study population.

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.

Community-onset Staphylococcus aureus infections presenting to general practices in South-eastern Australia.

Community-acquired Staphylococcus aureus infections are a public health concern, yet little is known about infections that do not present to hospital. We identified community-onset S. aureus infections via specimens submitted to a community-based pathology service. Referring doctors confirmed eligibility and described infection site, severity and treatment. Isolates were characterized on antibiotic resistance, PFGE, MLST/SCCmec, and Panton-Valentine leukocidin (PVL), representing 106 community-onset infections; 34 non-multiresistant methicillin-resistant S. aureus (nmMRSA) (resistant to <3 non-ß-lactam antibiotics), 15 multiply antibiotic-resistant MRSA (mMRSA) and 57 methicillin-sensitive S. aureus (MSSA). Most (93%) were skin and soft tissue infections. PVL genes were carried by 42% of nmMRSA isolates [95% confidence interval (CI) 26-61] and 15% of MSSA (95% CI 8-28). PVL was associated with infections of the trunk, head or neck (56·4% vs. 24·3%, P=0·005) in younger patients (23 vs. 52 years, P<0·001), and with boils or abscesses (OR 8·67, 95% CI 2·9-26·2), suggesting underlying differences in exposure and/or pathogenesis.

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.

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.

Vancomycin therapeutics and monitoring: a contemporary approach.

Vancomycin remains a clinically useful antibiotic despite the advent of several alternative drugs. Optimising vancomycin therapy with therapeutic drug monitoring is widely recommended. The aim of therapeutic drug monitoring is to help the clinician to achieve target pharmacodynamic parameters in the case of vancomycin, an area under the concentration time curve/minimum inhibitory concentration ratio of ≥400. Vancomycin monitoring methods can be categorised into four categories: empiric trough concentrations; linear regression analysis (one-compartment model), population methods and Bayesian estimation procedures. Although the empiric trough concentrations and population methods are easy to use and require minimal resources, there are large differences in the published vancomycin model parameters. This demonstrates that there is great variance in pharmacokinetic parameters between the models and a single vancomycin model cannot be applied to all patient populations. The linear regression and Bayesian methods recommended more accurate dosage regimens; however, they require additional resources such as information technology and healthcare personnel with background training in pharmacokinetics. The Bayesian methods offered additional advantages such as calculation of doses based on a single-serum concentration and optimisation of the patient's previous pharmacokinetic data to determine subsequent dosage regimens. Computerised programs, utilising the Bayesian estimation procedures, are able to achieve target concentrations in a greater percentage of patients earlier in the course of therapy than the empiric trough concentrations and population methods. We recommend the use of these programs providing there is appropriate expertise available to make appropriate recommendations.

Comparison of the bacterial isolates and antibiotic resistance patterns of elderly nursing home and general community patients.

BACKGROUND: Nursing home-acquired infections may differ from general community-acquired infections in bacteriology and antibiotic resistance. However, there are currently limited data on this topic in the Australian setting. AIMS: To compare bacterial isolates and antibiotic resistance patterns, from pathology specimens of nursing home and community patients, and to comment on the suitability of empiric antibiotic guidelines for nursing home-acquired infection. METHODS: This was a retrospective cohort study of patients, aged ≥ 65 years, who resided in either nursing homes or the general community. Patients with a hospital admission in the previous 28 days were excluded. Positive specimen cultures, collected between July 2003 and June 2008 in the Emergency Department and Outpatient Clinics of the Austin Hospital (Melbourne), were examined. The main outcome measures were the bacterial isolates, and their antibiotic resistance patterns, of patients from nursing homes and the general community. RESULTS: Specimens of blood (638), sputum (425), urine (4044) and wound cultures (785) were examined. The bacteriology of blood culture isolates did not differ between the two groups (P= 0.3). However, the bacteriology of sputum, urine and wound cultures differed significantly between the groups (P= 0.025, P < 0.001, P= 0.004 respectively). There were also higher proportions of antibiotic resistance among some bacteria in nursing home patients, especially methicillin resistance among Staphylococcus aureus isolates across all specimen types, and resistance to several empiric antibiotics among Enterobacteriaceae isolates in urine cultures. CONCLUSION: Empiric antibiotic guidelines appear adequate to treat nursing home-acquired septicaemia and pneumonia. However, guidelines for urinary tract infections and wound infections may need to be refined.