Variability in Azithromycin Susceptibility Results for Neisseria gonorrhoeae Obtained Using Gradient MIC Strip and Agar Dilution Techniques.

Azithromycin is a component of empirical treatment regimens for Neisseria gonorrhoeae infections, but antimicrobial susceptibility testing for this agent is technically challenging. We compared the intertest variability, MIC values, and CLSI/EUCAST categorization of clinical and reference isolates of N. gonorrhoeae treated with azithromycin by testing 107 clinical isolates and nine reference isolates by agar dilution and in duplicates using MIC test strips (Liofilchem, Italy) and Etests (bioMérieux, France). Replicate isolate agreement within 1 log2 between duplicate tests was 87% for MIC test strips and 100% for Etests (P < 0.001). Essential agreement with the agar dilution method was higher for Etests (91%) than for MIC test strips (44%, P < 0.001). The geometric mean MIC was highest for MIC test strips (0.8 mg/liter) and significantly higher than both Etest (0.47 mg/liter, P < 0.001) and agar dilution (0.26 mg/liter, P < 0.001) methods. Etest MICs were higher than those obtained with agar dilution (P < 0.001). Agar dilution, MIC test strip, and Etest methods categorized 96%, 85%, and 95% (P = 0.003) of clinical isolates, respectively, as susceptible/wild type according to CLSI/EUCAST criteria. Our results illustrate the difficulties underlying azithromycin susceptibility testing for N. gonorrhoeae and demonstrate that results can vary using different methods. This variability could influence antimicrobial resistance reporting between laboratories involved in N. gonorrhoeae surveillance programs.

Separate and interacting effects of the endogenous circadian system and behaviors on plasma aldosterone in humans.

Measurements of aldosterone for diagnosis of primary aldosteronism are usually made from blood sampled in the morning when aldosterone typically peaks. We tested the relative contributions and interacting influences of the circadian system, ongoing behaviors, and prior sleep to this morning peak in aldosterone. To determine circadian rhythmicity and separate effects of behaviors on aldosterone, 16 healthy participants completed a 5-day protocol in dim light while all behaviors ranging from sleep to exercise were standardized and scheduled evenly across the 24-h circadian period. In another experiment, to test the separate effects of prior nocturnal sleep or the inactivity that accompanies sleep on aldosterone, 10 healthy participants were studied across 2 nights: 1 with sleep and 1 with maintained wakefulness (randomized order). Plasma aldosterone was measured repeatedly in each experiment. Aldosterone had a significant endogenous rhythm ( P < 0.001), rising across the circadian night and peaking in the morning (~8 AM). Activity, including exercise, increased aldosterone, and different behaviors modulated aldosterone differently across the circadian cycle (circadian phase × behavior interaction; P < 0.001). In the second experiment, prior nocturnal sleep and prior rested wakefulness both increased plasma aldosterone ( P < 0.001) in the morning, to the same extent as the change in circadian phases between evening and morning. The morning increase in aldosterone is due to effects of the circadian system plus increased morning activities and not prior sleep or the inactivity accompanying sleep. These findings have implications for the time of and behaviors preceding measurement of aldosterone, especially under conditions of shift work and jet lag.

Morning impairment in vascular function is unrelated to overnight sleep or the inactivity that accompanies sleep.

Adverse cardiovascular events, such as myocardial infarction and sudden cardiac death, occur more frequently in the morning. Prior studies have shown that vascular endothelial function (VEF), a marker of cardiovascular disease, is attenuated during physical inactivity and declines across the night. We sought to determine whether a morning attenuation in VEF is a result of prior sleep or the inactivity that inevitably accompanies sleep. After 1 wk of a rigorously controlled sleep-wake schedule and behaviors, 10 healthy participants completed a randomized crossover protocol in dim light and constant conditions, incorporating a night of 6 h of sleep opportunity and a night of immobility while they were supine and awake. VEF was measured in the dominant brachial artery as flow mediated dilation (FMD) before and after each 6-h trial. To avoid disturbing sleep and posture of the participants, blood was drawn using a 12-ft catheter from an adjoining laboratory room before, during, and after each 6-h trial, and plasma was analyzed for markers of oxidative stress [malondialdehyde adducts (MDA)], and endothelin-1. Contrary to expectation, both nocturnal sleep and nocturnal inactivity significantly increased FMD ( P < 0.05). There was no significant change in MDA or endothelin-1 within and between trials. Contrary to expectations based on prior studies, we found that overnight sleep or the inactivity that accompanies sleep did not result in attenuation in VEF in the morning hours in healthy people. Thus, it is plausible that the endogenous circadian system, a remaining factor not studied here, is responsible for the commonly observed decline in VEF across the night.

Target-Specific Assay for Rapid and Quantitative Detection of Mycobacterium chimaera DNA.

Mycobacterium chimaera is an opportunistic environmental mycobacterium belonging to the Mycobacterium avium-M. intracellulare complex. Although most commonly associated with pulmonary disease, there has been growing awareness of invasive M. chimaera infections following cardiac surgery. Investigations suggest worldwide spread of a specific M. chimaera clone, associated with contaminated hospital heater-cooler units used during the surgery. Given the global dissemination of this clone, its potential to cause invasive disease, and the laboriousness of current culture-based diagnostic methods, there is a pressing need to develop rapid and accurate diagnostic assays specific for M. chimaera Here, we assessed 354 mycobacterial genome sequences and confirmed that M. chimaera is a phylogenetically coherent group. In silico comparisons indicated six DNA regions present only in M. chimaera We targeted one of these regions and developed a TaqMan quantitative PCR (qPCR) assay for M. chimaera with a detection limit of 100 CFU/ml in whole blood spiked with bacteria. In vitro screening against DNA extracted from 40 other mycobacterial species and 22 bacterial species from 21 diverse genera confirmed the in silico-predicted specificity for M. chimaera Screening 33 water samples from heater-cooler units with this assay highlighted the increased sensitivity of PCR compared to culture, with 15 of 23 culture-negative samples positive by M. chimaera qPCR. We have thus developed a robust molecular assay that can be readily and rapidly deployed to screen clinical and environmental specimens for M. chimaera.

Public health action following an outbreak of toxigenic cutaneous diphtheria in an Auckland refugee resettlement centre.

Global forced displacement has climbed to unprecedented levels due largely to regional conflict. Degraded public health services leave displaced people vulnerable to multiple environmental and infectious hazards including vaccine preventable disease. While diphtheria is rarely notified in New Zealand, a 2 person outbreak of cutaneous diphtheria occurred in refugees from Afghanistan in February 2015 at the refugee resettlement centre in Auckland. Both cases had uncertain immunisation status. The index case presented with a scalp lesion during routine health screen and toxigenic Corynebacterium diphtheriae was isolated. A secondary case of cutaneous diphtheria and an asymptomatic carrier were identified from skin and throat swabs. The 2 cases and 1 carrier were placed in consented restriction until antibiotic treatment and 2 clearance swabs were available. A total of 164 contacts were identified from within the same hostel accommodation as well as staff working in the refugee centre. All high risk contacts (n=101) were swabbed (throat, nasopharynx and open skin lesions) to assess C. diphtheriae carriage status. Chemoprophylaxis was administered (1 dose of intramuscular benzathine penicillin or 10 days of oral erythromycin) and diphtheria toxoid-containing vaccine offered regardless of immunisation status. Suspected cases were restricted on daily monitoring until swab clearance. A group of 49 low risk contacts were also offered vaccination. Results suggest a significant public health effort was required for a disease rarely seen in New Zealand. In light of increased worldwide forced displacement, similar outbreaks could occur and require a rigorous public health framework for management.

High usage of topical fusidic acid and rapid clonal expansion of fusidic acid-resistant Staphylococcus aureus: a cautionary tale.

Our aim was to assess national prescribing trends and determine longitudinal resistance patterns for topical antimicrobials in New Zealand. We observed a dramatic increase in fusidic acid (FA) resistance, and clonal expansion of FA-resistant Staphylococcus aureus. This increase was concurrent with a significant national increase in topical FA dispensing.

Staphylococcus aureus infections in New Zealand, 2000-2011.

The incidence rate for invasive and noninvasive Staphylococcus aureus infections in New Zealand is among the highest reported in the developed world. Using nationally collated hospital discharge data, we analyzed the epidemiology of serious S. aureus infections in New Zealand during 2000-2011. During this period, incidence of S. aureus skin and soft tissue infections increased significantly while incidence of staphylococcal sepsis and pneumonia remained stable. We observed marked ethnic and sociodemographic inequality across all S. aureus infections; incidence rates for all forms of S. aureus infections were highest among Maori and Pacific Peoples and among patients residing in areas of high socioeconomic deprivation. The increased incidence of S. aureus skin and soft tissue infections, coupled with the demographic disparities, is of considerable concern. Future work should aim to reduce this disturbing national trend.

Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates.

An elevated vancomycin MIC is associated with poor outcomes in Staphylococcus aureus bacteremia (SAB) and is reported in patients with methicillin-susceptible S. aureus (MSSA) bacteremia in the absence of vancomycin treatment. Here, using DNA microarray and phenotype analysis, we investigated the genetic predictors and accessory gene regulator (agr) function and their relationship with elevated vancomycin MIC using blood culture isolates from a multicenter binational cohort of patients with SAB. Specific clonal complexes were associated with elevated (clonal complex 8 [CC8] [P < 0.001]) or low (CC22 [P < 0.001], CC88 [P < 0.001], and CC188 [P = 0.002]) vancomycin MIC. agr dysfunction (P = 0.014) or agr genotype II (P = 0.043) were also associated with an elevated vancomycin MIC. Specific resistance and virulence genes were also linked to an elevated vancomycin MIC, including blaZ (P = 0.002), sea (P < 0.001), clfA (P < 0.001), splA (P = 0.001), and the arginine catabolic mobile element (ACME) locus (P = 0.02). These data suggest that inherent organism characteristics may explain the link between elevated vancomycin MICs and poor outcomes in patients with SAB, regardless of the antibiotic treatment received. A consideration of clonal specificity should be included in future research when attempting to ascertain treatment effects or clinical outcomes.

Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia.

A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ≥ 400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a "real-world" context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively; P < 0.001). Obtaining the recommended vancomycin target AUC/MIC of ≥ 400 using BMD was not associated with lower 30-day all-cause or attributable mortality from SAB (P = 0.132 and P = 0.273, respectively). However, an alternative vancomycin AUC/MIC of >373, derived using classification and regression tree analysis, was associated with reduced mortality (P = 0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ≥ 400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods.

Population-based incidence and comparative demographics of community-associated and healthcare-associated Escherichia coli bloodstream infection in Auckland, New Zealand, 2005-2011.

BACKGROUND: Escherichia coli is a major human pathogen, both in community and healthcare settings. To date however, relatively few studies have defined the population burden of E. coli bloodstream infections. Such information is important in informing strategies around treatment and prevention of these serious infections. Against this background, we performed a retrospective, population-based observational study of all cases of E. coli bacteremia in patients presenting to our hospital between January 2005 and December 2011. METHODS: Auckland District Health Board is a tertiary-level, university-affiliated institution serving a population of approximately 500,000, within a larger metropolitan population of 1.4 million. We identified all patients with an episode of bloodstream infection due to E. coli over the study period. A unique episode was defined as the first positive E. coli blood culture taken from the same patient within a thirty-day period. Standard definitions were used to classify episodes into community- or healthcare-associated E. coli bacteremia. Demographic information was obtained for all patients, including: age; gender; ethnicity; length of stay (days); requirement for intensive care admission and all-cause, in-patient mortality. RESULTS: A total of 1507 patients had a unique episode of E. coli bacteremia over the study period. The overall average annual incidence of E. coli bacteremia was 52 per 100,000 population, and was highest in the under one year and over 65-year age groups. When stratified by ethnicity, rates were highest in Pacific Peoples and Maori (83 and 62 per 100,000 population respectively). The incidence of community-onset E. coli bacteremia increased significantly over the study period. The overall in-hospital mortality rate was 9% (135/1507), and was significantly higher in patients who had a hospital-onset E. coli bacteremia. CONCLUSIONS: Our work provides valuable baseline data on the incidence of E. coli bacteremia in our locale. The incidence was higher that that described from other developed countries, with significant demographic variation, most notably in ethnic-specific incidence rates. Future work should assess the possible reasons for this disparity.

Incidence, trends and demographics of Staphylococcus aureus infections in Auckland, New Zealand, 2001-2011.

BACKGROUND: New Zealand has a higher incidence of Staphylococcus aureus disease than other developed countries, with significant sociodemographic variation in incidence rates. In contrast to North America, the majority of disease is due to methicillin-susceptible S. aureus (MSSA), although relatively little is known about the comparative demographics of MSSA and methicillin-resistant S. aureus (MRSA) infections in New Zealand. METHODS: Our objectives were to describe the trends, incidence and patient demographics of all S. aureus infections in patients presenting to our institution between 2001 and 2011, and compare the epidemiology of MSSA and MRSA infections. We identified all patients with S. aureus infections over the study period. A unique S. aureus infection was defined as the first positive S. aureus culture taken from the same patient within a thirty-day period. Standard definitions were used to classify episodes into community- or healthcare-associated S. aureus infection. RESULTS: There were 16,249 S. aureus infections over the study period. The incidence increased significantly over the study period from 360 to 412 per 100,000 population (P < 0.001), largely driven by an increase in community-associated non-invasive MSSA infections. When compared with MSSA infections, patients with non-multiresistant MRSA infections were more likely to be older, have hospital-onset infections and be Maori or Pacific Peoples. CONCLUSIONS: Our work provides valuable baseline data on the epidemiology and trends of S. aureus infections in New Zealand. The significant increase in community-associated S. aureus infections is of public health importance. Future studies should investigate the reasons underlying this concerning trend.

Species distribution and susceptibility of Nocardia isolates in New Zealand 2002-2021.

The aim was to record the distribution and susceptibility of Nocardia species in New Zealand. Local and referred isolates were identified by an evolving approach over the study period including conventional phenotypic methods, susceptibility profiles, matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF) and molecular sequencing. Isolates previously identified as a Nocardia sp. or part of the N. asteroides complex were reidentified by MALDI-TOF and/or molecular methods. Antimicrobial susceptibility to eight antibiotics was performed by standard microbroth dilution. The site of isolation, susceptibility profiles and species distribution were analysed. A total of 383 isolates were tested: N. brasiliensis 23 (6%), N. cyriacigeorgica 42 (11%), N. farcinica 41 (11%), N. nova complex 226 (59%), and 51 (13%) other species/complexes. The respiratory tract was the most common site of infection (244, 64%), with skin and soft tissue the second most common site (104, 27%). All 23 N. brasiliensis isolates were from skin and soft tissue specimens. Almost all isolates (≥98%) were susceptible to amikacin, linezolid and trimethoprim-sulfamethoxazole; 35% and 77% were resistant to clarithromycin and quinolones, respectively. The expected susceptibility profiles of the four common species and complex were observed for most agent-organism parings. Multi-drug resistance was uncommon (3.4%). The spectrum of Nocardia species in New Zealand is similar to overseas reports and our most common group is the N. nova complex. While amikacin, linezolid and trimethoprim-sulfamethoxazole remain good empiric treatment choices, other agents should have their activity confirmed before use.

Planning and executing a national point prevalence study: a blueprint for the future.

Healthcare-associated infections (HAIs) are a significant risk for patients and a burden on the health system. In 2021, the Te Tahu Hauora Health Quality & Safety Commission New Zealand Infection Prevention and Control Team undertook a national HAI point prevalence survey (PPS) across all 20 district health boards (DHBs). We describe the process that was undertaken to plan for and execute the PPS. The key stages of this project were planning, communication and engagement, piloting and then refining the process, training surveyors, delivering the full PPS, and finally, data analysis and reporting. Support for the PPS was received at a national level from clinical and non-clinical management. The sharing of this information may support other health provider groups to use similar methodology to better understand the epidemiology of both infectious and non-infectious diseases locally. It provides a useful planning strategy for those considering similar surveys.

Escherichia coli bloodstream infection after transrectal ultrasound-guided prostate biopsy: implications of fluoroquinolone-resistant sequence type 131 as a major causative pathogen.

BACKGROUND: Transrectal ultrasound-guided (TRUS) prostate biopsy is a commonly performed procedure, and fluoroquinolones are the most frequently given prophylactic antimicrobials. In the context of increasing fluoroquinolone resistance, and the international emergence of fluoroquinolone-resistant sequence type 131 (ST131) Escherichia coli, we describe a large series of E. coli bacteremia after TRUS biopsy. METHODS: All male patients admitted with community-onset (CO) E. coli bacteremia from January 2006 through December 2010 were included. Patient characteristics, treatment outcomes, and rates of antimicrobial resistance were compared between patients with TRUS biopsy-related bacteremia and other male patients with CO E. coli bacteremia. Molecular typing was performed on E. coli isolates to determine phylogenetic group. RESULTS: A total of 258 male patients were admitted with CO E. coli bacteremia. Of these, 47 patients (18%) were admitted after TRUS biopsy. Patients who had undergone TRUS biopsy were twice as likely to require intensive care admission (25% vs 12%) and had significantly higher rates of resistance to gentamicin (43%), trimethoprim-sulphamethoxazole (60%), and ciprofloxacin (62%) as well as all 3 agents in combination (19%). Thirty-six percent of post-TRUS biopsy patients did not receive active empirical antibiotic therapy. The ST131 clone accounted for 41% of all E. coli isolates after TRUS biopsy. CONCLUSIONS: E. coli bacteremia can be a life-threatening complication of TRUS biopsy. Infecting strains are frequently multidrug-resistant and resistant to common empirical antibiotic agents. E. coli ST131 is an important cause of sepsis after TRUS biopsy. Further studies should evaluate colonization with fluoroquinolone-resistant E. coli as a risk factor for postbiopsy sepsis.

Mycotic abdominal aortic aneurysm caused by toxigenic Clostridium difficile.

Extra-intestinal infections caused by Clostridium difficile are uncommon. We report a case of a mycotic abdominal aortic aneurysm in an 86-year old male. Tissue and pus swabs from the aneurysmal sac grew a pure growth of C. difficile. The identity of the isolate was determined by phenotypic methods and confirmed by DNA sequencing. He was treated successfully with an aorta-bifemoral bypass and a 4-week course of intravenous and oral antibiotics.

Antibiotic choice may not explain poorer outcomes in patients with Staphylococcus aureus bacteremia and high vancomycin minimum inhibitory concentrations.

BACKGROUND: There are concerns about reduced efficacy of vancomycin in patients with Staphylococcus aureus bacteremia (SAB), especially when the minimum inhibitory concentration (MIC) nears the upper limit of the susceptible range. METHODS: We examined the relationship between antibiotic treatment, 30-day mortality, and microbiologic parameters in a large Australasian cohort of patients with SAB. RESULTS: We assessed 532 patients with SAB from 8 hospitals. All patients with methicillin-resistant S. aureus (MRSA) bacteremia were treated with vancomycin, and patients with methicillin-susceptible S. aureus (MSSA) bacteremia received either flucloxacillin or vancomycin. Increasing vancomycin MIC was associated with increased mortality in vancomycin-treated patients. However, even in patients with MSSA bacteremia treated with flucloxacillin, mortality was also higher if the vancomycin Etest MIC of their isolate was >1.5 µg/mL, compared with those with lower MIC isolates (26.8% vs 12.2%; P < .001). After adjustment in a multivariate model, age, hospital-onset SAB and vancomycin MIC were independently associated with mortality, but methicillin resistance and antibiotic choice were not. CONCLUSIONS: We have confirmed an association between higher vancomycin MIC and increased mortality in patients with SAB, but surprisingly this relationship was not related to the antibiotic treatment received, suggesting that the use of vancomycin per se is not responsible for the poorer outcome.

Sources of healthcare-associated Staphylococcus aureus bacteraemia in New Zealand acute hospitals.

AIM: The primary aim of this study was to identify the source of healthcare-associated Staphylococcus aureus bacteraemia (HA-SAB) in acute district health board (DHB) hospitals to inform future national quality improvement activities. METHOD: De-identified HA-SAB event source information was submitted to the Commission from all DHBs for the period 1 January 2017 to 30 June 2021. Data was categorised and analysed to identify trends and significant sources of infection. RESULTS: There were 1,867 HA-SAB events. Of the events where S. aureus susceptibility results were reported, 159 (10%) isolates were methicillin-resistant S. aureus. The principal sources of HA-SAB were medical devices (65%), surgical site infection (10%), and organ site (8%). Ninety-five percent of medical devices were for vascular access, primarily central venous catheters (50%) and peripheral intravenous catheters (45%). CONCLUSION: This study has identified intravascular devices as significant sources of HA-SAB. Ongoing surveillance for HA-SAB source is required to identify the major risk factors and to support quality improvement activities targeting infection prevention measures and best practice related to intravascular and other medical devices.

Risk factors differ for Gram-negative surgical site infection following hip and knee arthroplasty: an observational study from a national surveillance system.

AIM: To describe risk factors for surgical site infection (SSI) caused by aerobic Gram-negative organisms after hip and knee arthroplasty. METHOD: Publicly funded hip and knee arthroplasties (performed between 1 July 2013 and 31 December 2017) that developed SSIs were compared to those that did not. SSIs were grouped by causative organism: Gram-negative (Pseudomonas spp. or enteric Gram-negative bacilli) or staphylococcal (pure or mixed growth of Staphylococcus spp.). Independent risk factors in each group were identified. RESULTS: 24,842 (54%) hip and 20,993 (46%) knee arthroplasties were performed. There were 497 (1.1%) SSIs. Staphylococci were responsible for 233 SSIs (47%) and Gram-negatives were responsible for 73 (15%). Age, sex, body mass index ≥35kg/m2, smoking status, socioeconomic deprivation, American Society of Anesthesiologists classification, revision surgery and prophylactic antibiotic dose were all independent predictors of all-cause SSI. On subgroup analysis, socioeconomic deprivation and Pasifika ethnicity were independent risk factors for Gram-negative SSI, but not staphylococcal SSI. DISCUSSION: In this study, socioeconomic deprivation and ethnicity were independent and novel risk factors for Gram-negative SSI following arthroplasty. Some of the SSI risk factors can be modified before arthroplasty (e.g., appropriate timing of prophylactic antibiotics, smoking cessation, weight loss). Non-modifiable risk factors can help identify high-risk procedures where additional pre- and post-operative interventions may be warranted.