An exception-reporting approach for wound swab culture: effect on post-report antibiotic initiation.

A prior analysis suggested that wound swab culture (WSC) results were driving unnecessary antibiotic use in patients who were not already receiving treatment. As a quality-improvement initiative, our laboratory introduced an "exception-reporting" protocol on 1 March 2023, whereby typical wound pathogens susceptible to recommended empiric therapy (flucloxacillin/cefalexin) were not reported, and a comment was provided, stating no significant resistant organisms had been detected. Full results were available to clinicians on request. Cultures falling outside protocol criteria were reported in the standard fashion. This analysis sought to assess the effect of exception-reporting on post-report antibiotic initiation (PRAI). All community WSC results were matched to antibiotic dispensing records from October 2021 to December 2023. Sampling without treatment pre-report was termed "test and wait" (TaW). Following TaW, PRAI was identified if antibiotics were started within 5 days post-report. There were 1,819 and 764 WSCs received in the pre-change and post-change periods, respectively, where an initial TaW approach had been taken and an organism eligible for exception-reporting had been isolated. In the post-change period, 407 (53.3%) met the criteria and were exception-reported. PRAI occurred in 901 (49.5%) pre-change samples, compared to 102 (25.1%, P < 0.01) with exception-reporting. There was no detectable increase in hospitalization or repeat WSC collection in the 30 days following exception-reporting. Exception-reporting was associated with a markedly reduced proportion of patients being initiated on antibiotics following WSC where an organism had been isolated. The naming of organisms in reports appears to drive unnecessary antibiotic prescribing in many patients. These results require confirmation in other jurisdictions. IMPORTANCE: Wound swab culture is a high-volume test performed in clinical microbiology laboratories. In this analysis, we have shown that an alternative approach to reporting positive wound swab cultures has resulted in a large reduction in post-report antibiotic initiation, suggesting that the current standard method of reporting generates considerable unnecessary antibiotic use. If these findings are replicated elsewhere, wider adoption of this reporting would represent an opportunity for many clinical microbiology laboratories to have a significant impact on community antimicrobial stewardship.

Effect of directive laboratory comments on prescribing response to positive throat swab cultures.

BACKGROUND: In patients without ethnicity risk factors for acute rheumatic fever (ARF), our local guidelines recommend limiting antibiotic use following a positive throat swab culture (TSC). If symptoms are severe, a 5-7 day course is recommended. Despite this, most local patients with a positive TSC for group A Streptococcus (GAS) or Streptococcus dysgalactiae subsp. equisimilis (SDSE) were being prescribed 10 days of antibiotics. In response, we added comments to positive TSC reports recommending shorter treatment durations in those without ARF risk factors. No other antimicrobial stewardship initiatives were implemented. OBJECTIVES: To assess the effect of these comments on antibiotic course duration after positive TSC. METHODS: All community TSC results from 1 October 2021 to 31 March 2023 (1 year pre- to 6 months post-change) were matched to antibiotic dispensing data. Patients who had been empirically dispensed an antibiotic prior to the culture report were excluded. The outcome of interest was the antibiotic duration dispensed in the 5 day period after the TSC report. RESULTS: Following introduction of the comments, median course duration reduced from 10 (IQR 5-10) to 7 days (IQR 0-10; P < 0.01) and from 7 (IQR 0-10) to 0 days (IQR 0-5; P < 0.01) following GAS- and SDSE-positive TSC, respectively, in those without ARF risk factors. The percentage of people receiving 10 days of antibiotics decreased from 63.0% to 37.0% (P < 0.01) and 41.2% to 14.6% (P < 0.01) for GAS and SDSE, respectively. CONCLUSIONS: The introduction of comments providing direct prescribing advice to requestors appears to have been highly effective at improving guideline-compliant prescribing following positive TSC report.

Post-report antibiotic initiation following community non-sterile-site microbiology results: an opportunity for labs to lead stewardship?

OBJECTIVES: Positive culture results from non-sterile sites (NSSs) are poorly predictive of clinical infection. Despite this, these results are often interpreted as an indication for antibiotics, even in patients with limited signs of infection. We sought to quantify the influence of NSS culture results on post-report antibiotic initiation (PRAI) in patients who had not been started on antibiotics pre-report. METHODS: All community wound/skin swab and sputum cultures were matched to antibiotic dispensing records from February 2017 to July 2022. Prescribing behaviour was assessed pre- and post-report. Sampling without treatment pre-report was termed 'test-and-wait' (TaW). Following TaW, PRAI was identified if antibiotics were started within 5 days post-report. RESULTS: There were 65 480 wound/skin swabs and 8126 sputum samples, with TaW occurring in 21 740 (35.1%) and 4185 (54.4%), respectively. Following a TaW approach PRAI occurred in 43.3% when an organism was reported, versus 10.8% (P < 0.01) for a 'no growth' report for wound/skin swabs. For the same comparison with sputum, PRAI occurred in 47.9% versus 10.8% (P < 0.01). On multivariate analysis reporting an organism remained strongly associated with PRAI. CONCLUSIONS: Reporting an organism in those not already on antibiotics was strongly associated with PRAI. We hypothesize that for many patients TaW suggests limited evidence of infection (i.e. insufficient to justify antibiotic treatment at time of sampling), meaning positive NSS results may be driving a considerable volume of potentially unnecessary antibiotic use. Further study on this topic is required, but strategies to reduce PRAI may offer laboratories an opportunity to meaningfully impact antimicrobial stewardship efforts.

Temporal changes in neutropenic blood culture isolates and disease associations: a single centre series of 1139 episodes.

Neutropenic infections are life-threatening and require empiric antibiotic treatment. We examined 1139 blood culture isolates from our institution over a 36-year period from neutropenic patients to examine temporal trends and disease associations. Positive associations were found between viridans streptococci and acute myeloid leukaemia, coagulase negative staphylococci and acute lymphoblastic leukaemia and Pseudomonas aeruginosa and indolent B-cell malignancies.

Supplementary testing is not required in the cobas 4800 CT/NG test for Neisseria gonorrhoeae weak-positive urogenital samples.

Weak-positive Neisseria gonorrhoeae nucleic acid amplification test results are difficult to interpret. We show that the frequency of unconfirmed N. gonorrhoeae results from the cobas 4800 test rises exponentially after 38.0 cycles, where the likelihood of an unconfirmed result exceeds 29%. Supplementary testing of such samples should be avoided; instead, treatment should be based on clinical pretest probability.

Incorporating patient, nursing and environmental factors into antimicrobial stewardship: effects of simplifying treatment from cefuroxime to ceftriaxone.

AIM: Our antimicrobial guidelines (AGs) were changed in 2021 to recommend once-daily ceftriaxone in place of three-times-daily cefuroxime as preferred cephalosporin. This analysis sought to assess the effects of this on incidence of Clostridioides difficile infection (CDI), third-generation cephalosporin-resistant Enterobacterales (3GCR-E) and resource utilisation. METHOD: Before and after analysis of 30-day CDI and 3GCR-E incidence following receipt of cefuroxime/ceftriaxone pre- and post-AG change. Total nursing time and waste production relating to cefuroxime/ceftriaxone delivery were calculated pre- and post-change. RESULTS: CDI incidence was 0.6% pre- and 1.0% post-change (adjusted odds ratio [aOR] 1.44, p=0.07) and 3GCR-E incidence 3.5% and 3.1% (aOR 0.90, p=0.33). Mean per-quarter estimated nursing administration time decreased from 2,065 to 1,163 hours (902 nurse-hour reduction) and antibiotic-related waste generation from 1,131kg to 748kg (383kg reduction). Overall days of therapy per-quarter of cefuroxime/ceftriaxone were unchanged between periods. CONCLUSION: This simplification of our AG from a three-times-daily to a once-daily antibiotic resulted in considerable savings for our hospital (roughly 1.7 full-time equivalent nurses and over a tonne of waste yearly), with no significant increases in CDI or 3GCR-E. The impact of dosing schedules on non-antibiotic-spectrum factors, such as nursing time and resource usage, is worthy of consideration when designing AGs.

Early identification of a ward-based outbreak of Clostridioides difficile using prospective multilocus sequence type-based Oxford Nanopore genomic surveillance.

OBJECTIVE: To describe an outbreak of sequence type (ST)2 Clostridioides difficile infection (CDI) detected by a recently implemented multilocus sequence type (MLST)-based prospective genomic surveillance system using Oxford Nanopore Technologies (ONT) sequencing. SETTING: Hemato-oncology ward of a public tertiary referral centre. METHODS: From February 2022, we began prospectively sequencing all C. difficile isolated from inpatients at our institution on the ONT MinION device, with the output being an MLST. Bed-movement data are used to construct real-time ST-specific incidence charts based on ward exposures over the preceding three months. RESULTS: Between February and October 2022, 76 of 118 (64.4%) CDI cases were successfully sequenced. There was wide ST variation across cases and the hospital, with only four different STs being seen in >4 patients. A clear predominance of ST2 CDI cases emerged among patients with exposure to our hemato-oncology ward between May and October 2022, which totalled ten patients. There was no detectable rise in overall CDI incidence for the ward or hospital due to the outbreak. Following a change in cleaning product to an accelerated hydrogen peroxide wipe and several other interventions, no further outbreak-associated ST2 cases were detected. A retrospective phylogenetic analysis using original sequence data showed clustering of the suspected outbreak cases, with the exception of two cases that were retrospectively excluded from the outbreak. CONCLUSIONS: Prospective genomic surveillance of C. difficile using ONT sequencing permitted the identification of an outbreak of ST2 CDI that would have otherwise gone undetected.

Impact of the COVID-19 related border restrictions on influenza and other common respiratory viral infections in New Zealand.

BACKGROUND: New Zealand's (NZ) complete absence of community transmission of influenza and respiratory syncytial virus (RSV) after May 2020, likely due to COVID-19 elimination measures, provided a rare opportunity to assess the impact of border restrictions on common respiratory viral infections over the ensuing 2 years. METHODS: We collected the data from multiple surveillance systems, including hospital-based severe acute respiratory infection surveillance, SHIVERS-II, -III and -IV community cohorts for acute respiratory infection (ARI) surveillance, HealthStat sentinel general practice (GP) based influenza-like illness surveillance and SHIVERS-V sentinel GP-based ARI surveillance, SHIVERS-V traveller ARI surveillance and laboratory-based surveillance. We described the data on influenza, RSV and other respiratory viral infections in NZ before, during and after various stages of the COVID related border restrictions. RESULTS: We observed that border closure to most people, and mandatory government-managed isolation and quarantine on arrival for those allowed to enter, appeared to be effective in keeping influenza and RSV infections out of the NZ community. Border restrictions did not affect community transmission of other respiratory viruses such as rhinovirus and parainfluenza virus type-1. Partial border relaxations through quarantine-free travel with Australia and other countries were quickly followed by importation of RSV in 2021 and influenza in 2022. CONCLUSION: Our findings inform future pandemic preparedness and strategies to model and manage the impact of influenza and other respiratory viral threats.

Progression from new methicillin-resistant Staphylococcus aureus colonisation to infection: an observational study in a hospital cohort.

BACKGROUND: Patients newly colonised with methicillin-resistant Staphylococcus aureus (MRSA) are at higher risk of clinical MRSA infection. At present, there are limited data on the duration or magnitude of this risk in a hospital population with a known time of MRSA acquisition. METHODS: A retrospective cohort study of 909 adult patients known to have newly identified MRSA colonisation during admission to National University Hospital, Singapore between 1 July 2007 and 30 June 2011 was undertaken. Patients were excluded if they had history of previous MRSA colonisation or infection, or if they had been a hospital inpatient in the preceding 12 months. Data were collected on the development of MRSA infection requiring hospitalisation up to 30 June 2012. RESULTS: Of 840 patients newly colonised with MRSA as identified on active surveillance and not clinical specimens, 546 were men (65.0%) and the median age was 65 years (range 18-103 years). Median follow up was 24 months (range 0 -64 months, 85.1% followed >6 months). Clinical infection occurred in 121 patients (14.4%) with median time to infection of 22 days (95% CI 14-31). Overall 71.9% (87/121) of infected patients developed infection within 60 days of the date MRSA colonisation was detected. However, 17/121 patients (14.0%) developed clinical infection more than six months after documented MRSA acquisition. The most common sites of clinical infection were skin and soft tissue (49/121, 40.5%, 95% CI 31.7-49.8), respiratory tract (37/121, 30.6%, 95% CI 22.5-39.6) and bone and joint infections (14/121, 11.6%, 95% CI 6.5-18.7). Thirteen patients (13/121, 10.7%, 95% CI 5.8-17.7) had bacteraemias, of which six (5.0% 95% CI 1.8-10.5) were primary and seven (5.7%, 95% CI 2.3-11.6) were secondary to infection at other sites. Crude mortality at 30 days and six months was higher in patients with MRSA infection than colonisation alone (aOR 5.49, 95% CI 2.75-10.95, p<0.001 and aOR 2.94, 95% CI 1.78-4.85, p<0.001 respectively). CONCLUSION: Risk of clinical infection is highest soon after MRSA acquisition. Prevention of MRSA acquisition in hospital will have significant impact on morbidity and mortality for patients.

OXA-181-producing Klebsiella pneumoniae establishing in Singapore.

BACKGROUND: Carbapenemase producing Enterobacteriaceae are becoming a major public health concern globally, however, relatively little is known about the molecular and clinical epidemiology of these organisms in many parts of the world. METHODS: As part of a laboratory surveillance programme, 96 carbapenem non-susceptible Enterobacteriaceae isolates from clinical samples from patients in seven hospitals were referred for investigation for carbapenemases. Using polymerase chain reaction (PCR) to screen for a collection of genes encoding carbapenemases, 33 of 96 (34.5%) isolates were confirmed as carbapenemase producers. NDM-1 producers were the most prevalent at 64% (21/33) whilst OXA-181 was the second most common carbapenemase constituting 24.5% (8/33) of the carbapenemase producing isolates. Seven of these eight OXA-181 positive isolates underwent further characterisation with screening for other transmissible antimicrobial resistance determinants using PCR. Clonal relatedness was explored using Multilocus sequence typing (MLST) and Pulsed Field Gel Electrophoresis (PFGE). Plasmid characterisation was performed including restriction analysis and transfer by conjugation or transformation. RESULTS: In addition to the OXA-181 gene, all contained other transmissible resistance determinants including extended spectrum ß-lactamases, oxacillinases or 16S rRNA methylase genes, but none contained metallo-ß-lactamases or serine carbapenemases. All isolates had a multidrug resistant phenotype with two isolates being resistant to every antibiotic tested including colistin. Multilocus sequence typing confirmed five isolates belonged to ST17 and two to ST14, with those belonging to the same sequence type having identical PFGE profiles. The OXA-181 gene was typically carried on large plasmids which were mostly non-conjugative. CONCLUSIONS: OXA-181 carbapenemase appears to be an important and probably under-recognised cause of carbapenem resistance in Enterobacteriaceae in Singapore. Further coordinated research into clinical and molecular epidemiology of carbapenemases is urgently required in Singapore and throughout Asia.

Evolving swabbing practices for COVID-19 in a New Zealand emergency department during the early stages of an emerging pandemic.

OBJECTIVE: To review if tests for suspected COVID-19 were performed according to the Ministry of Health (MoH) case definitions, identify patterns associated with testing outside of the case definition, and discuss the potential impacts on hospital services. METHODS: This was a retrospective audit of patients presenting to the Wellington Hospital ED between 24 March 2020 and 27 April 2020 who were swabbed for COVID-19 in ED. Swabs were audited against the March 15th and April 8th MoH COVID-19 case definitions. RESULTS: Five hundred and thirty-six COVID-19 swabs for 518 patients were taken during the study period. There was poor alignment of testing with the March 15th case definition, with only 11.6% of the 164 swabs taken during this period meeting the case definition. Of the 145 swabs that did not meet the case definition, the majority (n = 119, 82.1%) met symptom criteria only. Alignment of testing with the wider April 8th case definition was much higher with 88.2% meeting criteria. Factors associated with being swabbed despite not meeting the case definitions included fever >38°, a diagnosis of cancer, subsequent hospital admission, and for the March case definition only 'contact with a traveller'. CONCLUSION: There were associations found between testing outside of criteria and specific variables potentially perceived as high-risk. Poor alignment of testing with case definitions can impact hospital services through the (mis)use of limited laboratory testing capacity and implications for resource management. Improved communication and feedback between clinicians and policymakers may improve case definition implementation in a clinical setting.

Molecular characterization of newly emerged blaKPC-2-producing Klebsiella pneumoniae in Singapore.

In Asia, bla(KPC) detection has been limited to East Asia and not yet seen in Southeast Asia. We report four bla(KPC-2)-containing Klebsiella pneumoniae isolates from two different hospitals in Singapore. All isolates belonged to strain type 11 (ST11) and were indistinguishable by pulsed-field gel electrophoresis (PFGE). bla(KPC-2) was located on nonconjugative plasmids and flanked by mobile genetic structures composed of a partial Tn4401 transposon and a Tn3-based transposon which previously have been described only in Chinese isolates.

A diagnostic polymerase chain reaction assay for Zika virus.

Zika virus (ZIKV) is a mosquito-borne flavivirus. Infection results in a dengue-like illness with fever, headache, malaise, and a maculopapular rash. Nearly all cases are mild and self-limiting but in 2007, a large outbreak of ZIKV was reported from the island of Yap (in Micronesia, northwest of Indonesia). Singapore is already endemic for dengue, and its impact on public health and economic burden is significant. Other dengue-like infections (e.g., Chikungunya virus) are present. Yet only 10% of reported dengue cases have laboratory confirmation. The identification and control of other dengue-like, mosquito-transmitted infections is thus important for the health of Singapore's population, as well as its economy. Given that ZIKV shares the same Aedes mosquito vector with both dengue and Chikungunya, it is possible that this virus is present in Singapore and causing some of the mild dengue-like illness. A specific and sensitive one-step, reverse transcription polymerase chain reaction (RT-PCR) with an internal control (IC) was designed and tested on 88 archived samples of dengue-negative, Chikungunya-negative sera from patients presenting to our hospital with a dengue-like illness, to determine the presence of ZIKV in Singapore. The assay was specific for detection of ZIKV and displayed a lower limit of detection (LoD) of 140 copies viral RNA/reaction when tested on synthetic RNA standards prepared using pooled negative patient plasma. Of the 88 samples tested, none were positive for ZIKV RNA, however, the vast majority of these were from patients admitted to hospital and further study may be warranted in community-based environments.

Effect of Blood Culture Contamination on Antibiotic Use in an Institution With Rapid Laboratory Methods and Phone-Based Clinical Follow-up of Blood Culture Results.

In a multivariate analysis of 30 574 blood culture (BC) results, BC contamination was associated with only a small increase in antibiotic length of therapy compared to no-growth BCs (difference, 0.36 days [95% confidence interval, .05-.67]; P = .02). Stewardship processes at our institution appear to be effective in reducing the impact of BC contamination.

Impact of the COVID-19 nonpharmaceutical interventions on influenza and other respiratory viral infections in New Zealand.

Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats.

Impact of the COVID-19 nonpharmaceutical interventions on influenza and other respiratory viral infections in New Zealand.

Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats.

The design, validation and clinical verification of an in-house qualitative PCR to detect Yersinia enterocolitica and Yersinia pseudotuberculosis in faeces.

Yersiniosis is a zoonotic foodborne infection of public health significance. The aim of this study was to design and validate a simple, accurate and cost-effective polymerase chain reaction (PCR) to detect pathogenic Yersinia spp. in faecal samples. An intercalating dye (EvaGreen)-based real-time multiplex PCR assay was designed to detect yadA, ystB and inv by melt curve analysis, allowing undifferentiated detection of all Yersinia enterocolitica biotypes, including biotype 1A, and Yersinia pseudotuberculosis. The assay was validated using cultured bacteria and clinical samples. A total of 107 positive and 51 negative samples were tested. The sensitivity and specificity was 98% and 100%. The limit of detection was 104-105 CFU/g faeces. A total of 605 samples (9 positive) were tested in the clinical verification with an accuracy and negative predictive value of 99% [95% confidence interval (CI) 97.9-99.6%] and 99.8% (95% CI 97.9-99.6%), respectively. This is an accurate, simple and cost-effective assay for the detection of pathogenic Yersinia spp.

The burden of Legionnaires' disease in New Zealand (LegiNZ): a national surveillance study.

BACKGROUND: Legionnaires' disease is under-diagnosed because of inconsistent use of diagnostic tests and uncertainty about whom to test. We assessed the increase in case detection following large-scale introduction of routine PCR testing of respiratory specimens in New Zealand. METHODS: LegiNZ was a national surveillance study done over 1-year in which active case-finding was used to maximise the identification of cases of Legionnaires' disease in hospitals. Respiratory specimens from patients of any age with pneumonia, who could provide an eligible lower respiratory specimen, admitted to one of 20 participating hospitals, covering a catchment area of 96% of New Zealand's population, were routinely tested for legionella by PCR. Additional cases of Legionnaires' disease in hospital were identified through mandatory notification. FINDINGS: Between May 21, 2015, and May 20, 2016, 5622 eligible specimens from 4862 patients were tested by PCR. From these, 197 cases of Legionnaires' disease were detected. An additional 41 cases were identified from notification data, giving 238 cases requiring hospitalisation. The overall incidence of Legionnaires' disease cases in hospital in the study area was 5·4 per 100 000 people per year, and Legionella longbeachae was the predominant cause, found in 150 (63%) of 238 cases. INTERPRETATION: The rate of notified disease during the study period was three-times the average over the preceding 3 years. Active case-finding through systematic PCR testing better clarified the regional epidemiology of Legionnaires' disease and uncovered an otherwise hidden burden of disease. These data inform local Legionnaires' disease testing strategies, allow targeted antibiotic therapy, and help identify outbreaks and effective prevention strategies. The same approach might have similar benefits if applied elsewhere in the world. FUNDING: Health Research Council of New Zealand.