The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis ...has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs.
We used a multicriteria decision analysis method to prioritise antibiotic-resistant bacteria; this method involved the identification of relevant criteria to assess priority against which each antibiotic-resistant bacterium was rated. The final priority ranking of the antibiotic-resistant bacteria was established after a preference-based survey was used to obtain expert weighting of criteria.
We selected 20 bacterial species with 25 patterns of acquired resistance and ten criteria to assess priority: mortality, health-care burden, community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in the community setting, preventability in the health-care setting, treatability, and pipeline. We stratified the priority list into three tiers (critical, high, and medium priority), using the 33rd percentile of the bacterium's total scores as the cutoff. Critical-priority bacteria included carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae. The highest ranked Gram-positive bacteria (high priority) were vancomycin-resistant Enterococcus faecium and meticillin-resistant Staphylococcus aureus. Of the bacteria typically responsible for community-acquired infections, clarithromycin-resistant Helicobacter pylori, and fluoroquinolone-resistant Campylobacter spp, Neisseria gonorrhoeae, and Salmonella typhi were included in the high-priority tier.
Future development strategies should focus on antibiotics that are active against multidrug-resistant tuberculosis and Gram-negative bacteria. The global strategy should include antibiotic-resistant bacteria responsible for community-acquired infections such as Salmonella spp, Campylobacter spp, N gonorrhoeae, and H pylori.
World Health Organization.
Penicillin allergies are associated with inferior patient and antimicrobial stewardship outcomes. We implemented a whole-of-hospital program to assess the efficacy of inpatient delabeling for ...low-risk penicillin allergies in hospitalized inpatients.
Patients ≥ 18 years of age with a low-risk penicillin allergy were offered a single-dose oral penicillin challenge or direct label removal based on history (direct delabeling). The primary endpoint was the proportion of patients delabeled. Key secondary endpoints were antibiotic utilization pre- (index admission) and post-delabeling (index admission and 90 days).
Between 21 January 2019 and 31 August 2019, we assessed 1791 patients reporting 2315 antibiotic allergies, 1225 with a penicillin allergy. Three hundred fifty-five patients were delabeled: 161 by direct delabeling and 194 via oral penicillin challenge. Ninety-seven percent (194/200) of patients were negative upon oral penicillin challenge. In the delabeled patients, we observed an increase in narrow-spectrum penicillin usage (adjusted odds ratio OR, 10.51 95% confidence interval {CI}, 5.39-20.48), improved appropriate antibiotic prescribing (adjusted OR, 2.13 95% CI, 1.45-3.13), and a reduction in restricted antibiotic usage (adjusted OR, 0.38 95% CI, .27-.54). In the propensity score analysis, there was an increase in narrow-spectrum penicillins (OR, 10.89 95% CI, 5.09-23.31) and β-lactam/β-lactamase inhibitors (OR, 6.68 95% CI, 3.94-11.35) and a reduction in restricted antibiotic use (OR, 0.52 95% CI, .36-.74) and inappropriate prescriptions (relative risk ratio, 0.43 95% CI, .26-.72) in the delabeled group compared with the group who retained their allergy label.
This health services program using a combination of direct delabeling and oral penicillin challenge resulted in significant impacts on the use of preferred antibiotics and appropriate prescribing.
Abstract
Carbapenem-resistant Enterobacteriaceae (CRE), Acinetobacter baumannii (CRAB), and Pseudomonas aeruginosa (CRPsA) are a serious cause of healthcare-associated infections, although the ...evidence for their control remains uncertain. We conducted a systematic review and reanalysis to assess infection prevention and control (IPC) interventions on CRE-CRAB-CRPsA in inpatient healthcare facilities to inform World Health Organization guidelines. Six major databases and conference abstracts were searched. Before-and-after studies were reanalyzed as interrupted time series if possible. Effective practice and organization of care (EPOC) quality criteria were used. Seventy-six studies were identified, of which 17 (22%) were EPOC-compatible and interrupted time series analyses, assessing CRE (n = 11; 65%), CRAB (n = 5; 29%) and CRPsA (n = 3; 18%). IPC measures were often implemented using a multimodal approach (CRE: 10/11; CRAB: 4/5; CRPsA: 3/3). Among all CRE-CRAB-CRPsA EPOC studies, the most frequent intervention components included contact precautions (90%), active surveillance cultures (80%), monitoring, audit and feedback of measures (80%), patient isolation or cohorting (70%), hand hygiene (50%), and environmental cleaning (40%); nearly all studies with these interventions reported a significant reduction in slope and/or level. The quality of EPOC studies was very low to low.
A systematic review and reanalysis found that infection prevention and control strategies including contact precautions, active surveillance cultures, monitoring, audit and feedback, patient isolation or cohorting, hand hygiene, and environmental cleaning were critical to the control of nosocomial carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa.
Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to ...health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline.
Background. Although pandemic and avian influenza are known to be transmitted via human hands, there are minimal data regarding the effectiveness of routine hand hygiene (HH) protocols against ...pandemic and avian influenza. Methods. Twenty vaccinated, antibody-positive health care workers had their hands contaminated with 1 mL of 107 tissue culture infectious dose (TCID)>50/0.1 mL live human influenza A virus (H1N1; A/New Caledonia/20/99) before undertaking 1 of 5 HH protocols (no HH control, soap and water hand washing SW, or use of 1 of 3 alcohol-based hand rubs 61.5% ethanol gel, 70% ethanol plus 0.5% chlorhexidine solution, or 70% isopropanol plus 0.5% chlorhexidine solution). H1N1 concentrations were assessed before and after each intervention by viral culture and real-time reverse-transcriptase polymerase chain reaction (PCR). The natural viability of H1N1 on hands for >60 min without HH was also assessed. Results. There was an immediate reduction in culture-detectable and PCR-detectable H1N1 after brief cutaneous air drying—14 of 20 health care workers had H1N1 detected by means of culture (mean reduction, 103–4 TCID>50/0.1 mL), whereas 6 of 20 had no viable H1N1 recovered; all 20 health care workers had similar changes in PCR test results. Marked antiviral efficacy was noted for all 4 HH protocols, on the basis of culture results (14 of 14 had no culturable H1N1; P<.002) and PCR results (P<.001; cycle threshold value range, 33.3–39.4), with SW statistically superior (P<.001) to all 3 alcohol-based hand rubs, although the actual difference was only 1–100 virus copies/µL. There was minimal reduction in H1N1 after 60 min without HH. Conclusions. HH with SW or alcohol-based hand rub is highly effective in reducing influenza A virus on human hands, although SW is the most effective intervention. Appropriate HH may be an important public health initiative to reduce pandemic and avian influenza transmission.
Vancomycin-resistant enterococci (VRE) are one of the leading causes of nosocomial infections in health care facilities around the globe. In particular, infections caused by vancomycin-resistant ...Enterococcus faecium are becoming increasingly common. Comparative and functional genomic studies of E. faecium isolates have so far been limited owing to the lack of a fully assembled E. faecium genome sequence. Here we address this issue and report the complete 3.0-Mb genome sequence of the multilocus sequence type 17 vancomycin-resistant Enterococcus faecium strain Aus0004, isolated from the bloodstream of a patient in Melbourne, Australia, in 1998. The genome comprises a 2.9-Mb circular chromosome and three circular plasmids. The chromosome harbors putative E. faecium virulence factors such as enterococcal surface protein, hemolysin, and collagen-binding adhesin. Aus0004 has a very large accessory genome (38%) that includes three prophage and two genomic islands absent among 22 other E. faecium genomes. One of the prophage was present as inverted 50-kb repeats that appear to have facilitated a 683-kb chromosomal inversion across the replication terminus, resulting in a striking replichore imbalance. Other distinctive features include 76 insertion sequence elements and a single chromosomal copy of Tn1549 containing the vanB vancomycin resistance element. A complete E. faecium genome will be a useful resource to assist our understanding of this emerging nosocomial pathogen.
Vancomycin-resistant Enterococcus faecium (VREfm) is a major nosocomial pathogen. Identifying VREfm transmission dynamics permits targeted interventions, and while genomics is increasingly being ...utilised, methods are not yet standardised or optimised for accuracy. We aimed to develop a standardized genomic method for identifying putative VREfm transmission links. Using comprehensive genomic and epidemiological data from a cohort of 308 VREfm infection or colonization cases, we compared multiple approaches for quantifying genetic relatedness. We showed that clustering by core genome multilocus sequence type (cgMLST) was more informative of population structure than traditional MLST. Pairwise genome comparisons using split k-mer analysis (SKA) provided the high-level resolution needed to infer patient-to-patient transmission. The more common mapping to a reference genome was not sufficiently discriminatory, defining more than three times more genomic transmission events than SKA (3729 compared to 1079 events). Here, we show a standardized genomic framework for inferring VREfm transmission that can be the basis for global deployment of VREfm genomics into routine outbreak detection and investigation.
Background. Despite the high prevalence of patient-reported antibiotic allergy (so-called antibiotic allergy labels AALs) and their impact on antibiotic prescribing, incorporation of antibiotic ...allergy testing (AAT) into antimicrobial stewardship (AMS) programs (AAT-AMS) is not widespread. We aimed to evaluate the impact of an AAT-AMS program on AAL prevalence, antibiotic usage, and appropriateness of prescribing. Methods. AAT-AMS was implemented at two large Australian hospitals during a 14-month period beginning May 2015. Baseline demographics, AAL history, age-adjusted Charlson comorbidity index, infection history, and antibiotic usage for 12 months prior to testing (pre–AAT-AMS) and 3 months following testing (post–AAT-AMS) were recorded for each participant. Study outcomes included the proportion of patients who were "de-labeled" of their AAL, spectrum of antibiotic courses pre– and post–AAT-AMS, and antibiotic appropriateness (using standard definitions). Results. From the 118 antibiotic allergy—tested patients, 226 AALs were reported (mean, 1.91/patient), with 53.6% involving 1 or more penicillin class drug. AAT-AMS allowed AAL de-labeling in 98 (83%) patients–56% (55/98) with all AALs removed. Post– AAT, prescribing of narrow-spectrum penicillins was more likely (adjusted odds ratio aOR, 2.81, 95% confidence interval CI, 1.45–5.42), as was narrow-spectrum β-lactams (aOR, 3.54; 95% CI, 1.98–6.33), and appropriate antibiotics (aOR, 12.27; 95% CI, 5.00–30.09); and less likely for restricted antibiotics (aOR, 0.16; 95% CI, 09–.29), after adjusting for indication, Charlson comorbidity index, and care setting. Conclusions. An integrated AAT-AMS program was effective in both de-labeling of AALs and promotion of improved antibiotic usage and appropriateness, supporting the routine incorporation of AAT into AMS programs.
The National Hand Hygiene Initiative (NHHI) is a standardised culture-change programme based on the WHO My 5 Moments for Hand Hygiene approach to improve hand hygiene compliance among Australian ...health-care workers and reduce the risk of health-care-associated infections. We analysed its effectiveness.
In this longitudinal study, we assessed outcomes of the NHHI for the 8 years after implementation (between Jan 1, 2009, and June 30, 2017), including hospital participation, hand hygiene compliance (measured as the proportion of observed Moments) three times per year, educational engagement, cost, and association with the incidence of health-care-associated Staphylococcus aureus bacteraemia (HA-SAB).
Between 2009 and 2017, increases were observed in national health-care facility participation (105 hospitals 103 public and two private in 2009 vs 937 hospitals 598 public and 339 private in 2017) and overall hand hygiene compliance (36 213 63·6% of 56 978 Moments 95% CI 63·2–63·9 in 2009 vs 494 673 84·3% of 586 559 Moments 84·2–84·4 in 2017; p<0·0001). Compliance also increased for each Moment type and for each health-care worker occupational group, including for medical staff (4377 50·5% of 8669 Moments 95% CI 49·4–51·5 in 2009 vs 53 620 71·7% of 74 788 Moments 71·4–72·0; p<0·0001). 1 989 713 NHHI online learning credential programmes were completed. The 2016 NHHI budget was equivalent to AUD$0·06 per inpatient admission nationally. Among Australia's major public hospitals (n=132), improved hand hygiene compliance was associated with declines in the incidence of HA-SAB (incidence rate ratio 0·85; 95% CI 0·79–0·93; p≤0·0001): for every 10% increase in hand hygiene compliance, the incidence of HA-SAB decreased by 15%.
The NHHI has been associated with significant sustained improvement in hand hygiene compliance and a decline in the incidence of HA-SAB. Key features include sustained central coordination of a standardised approach and incorporation into hospital accreditation standards. The NHHI could be emulated in other national culture-change programmes.
Australian Commission on Safety and Quality in Health Care.
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