Effectiveness and Safety of Measures to Prevent Infections and Other Complications Associated With Peripheral Intravenous Catheters: A Systematic Review and Meta-analysis.

BACKGROUND: Peripheral intravenous catheters (PIVCs) contribute substantially to the global burden of infections. This systematic review assessed 24 infection prevention and control (IPC) interventions to prevent PIVC-associated infections and other complications. METHODS: We searched Ovid MEDLINE, Embase, Cochrane Library, WHO Global Index Medicus, CINAHL, and reference lists for controlled studies from 1 January 1980-16 March 2023. We dually selected studies, assessed risk of bias, extracted data, and rated the certainty of evidence (COE). For outcomes with 3 or more trials, we conducted Bayesian random-effects meta-analyses. RESULTS: 105 studies met our prespecified eligibility criteria, addressing 16 of the 24 research questions; no studies were identified for 8 research questions. Based on findings of low to high COE, wearing gloves reduced the risk of overall adverse events related to insertion compared with no gloves (1 non-randomized controlled trial [non-RCT]; adjusted risk ratio [RR], .52; 95% CI, .33-.85), and catheter removal based on defined schedules potentially resulted in a lower phlebitis/thrombophlebitis incidence (10 RCTs; RR, 0.74, 95% credible interval, .49-1.01) compared with clinically indicated removal in adults. In neonates, chlorhexidine reduced the phlebitis score compared with non-chlorhexidine-containing disinfection (1 RCT; 0.14 vs 0.68; P = .003). No statistically significant differences were found for other measures. CONCLUSIONS: Despite their frequent use and concern about PIVC-associated complications, this review underscores the urgent need for more high-quality studies on effective IPC methods regarding safe PIVC management. In the absence of valid evidence, adherence to standard precaution measures and documentation remain the most important principles to curb PIVC complications. CLINICAL TRIALS REGISTRATION: The protocol was registered in the Open Science Framework (https://osf.io/exdb4).

The Penicillin Allergy Delabeling Program: A Multicenter Whole-of-Hospital Health Services Intervention and Comparative Effectiveness Study.

BACKGROUND: 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. METHODS: 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). RESULTS: 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 ß-lactam/ß-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. CONCLUSIONS: 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.

Control of Carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa in Healthcare Facilities: A Systematic Review and Reanalysis of Quasi-experimental Studies.

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.

Impact of an Integrated Antibiotic Allergy Testing Program on Antimicrobial Stewardship: A Multicenter Evaluation.

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 ß-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.

Fosfomycin for Treatment of Prostatitis: New Tricks for Old Dogs.

Treatment options for prostatitis caused by multidrug-resistant gram-negative bacilli are limited. We report two cases cured with oral fosfomycin and provide a pharmacokinetic analysis of fosfomycin predose concentrations during treatment.

Optimal timing of oral fosfomycin administration for pre-prostate biopsy prophylaxis.

OBJECTIVES: As the optimal administration time for fosfomycin peri-procedural prophylaxis is unclear, we sought to determine optimal administration times for fosfomycin peri-procedural prophylaxis. METHODS: Plasma, peripheral zone and transition zone fosfomycin concentrations were obtained from 26 subjects undergoing transurethral resection of the prostate (TURP), following a single oral dose of 3 g of fosfomycin. Population pharmacokinetic modelling was completed with the Nonparametric Adaptive Grid (NPAG) algorithm (Pmetrics package for R), with a four-compartment model. Plasma and tissue concentrations were simulated during the first 24 h post-dose, comparing these with EUCAST susceptibility breakpoints for Escherichia coli, a common uropathogen. RESULTS: Non-compartmental-determined pharmacokinetic values in our population were similar to those reported in the package insert. Predicted plasma concentrations rapidly increased after the first hour, giving more than 90% population coverage for organisms with an MIC ≤4 mg/L over the first 12 h post-dose. Organisms with higher MICs fared much worse, with organisms at the EUCAST breakpoint being covered for <10% of the population at any time. Transitional zone prostate concentrations exceeded 4 mg/L for 90% of the population between hours 1 and 9. Peripheral zone prostate concentrations were much lower and only exceeded 4 mg/L for 70% of the population between hours 1 and 4. CONCLUSIONS: Until more precise plasma and tissue data are available, we recommend that fosfomycin prophylaxis be given 1-4 h prior to prostate biopsy. We do not recommend fosfomycin prophylaxis for subjects with known organisms with MICs >4 mg/L.

Clinical population pharmacokinetics and toxicodynamics of linezolid.

Thrombocytopenia is a common side effect of linezolid, an oxazolidinone antibiotic often used to treat multidrug-resistant Gram-positive bacterial infections. Various risk factors have been suggested, including linezolid dose and duration of therapy, baseline platelet counts, and renal dysfunction; still, the mechanisms behind this potentially treatment-limiting toxicity are largely unknown. A clinical study was conducted to investigate the relationship between linezolid pharmacokinetics and toxicodynamics and inform strategies to prevent and manage linezolid-associated toxicity. Forty-one patients received 42 separate treatment courses of linezolid (600 mg every 12 h). A new mechanism-based, population pharmacokinetic/toxicodynamic model was developed to describe the time course of plasma linezolid concentrations and platelets. A linezolid concentration of 8.06 mg/liter (101% between-patient variability) inhibited the synthesis of platelet precursor cells by 50%. Simulations predicted treatment durations of 5 and 7 days to carry a substantially lower risk than 10- to 28-day therapy for platelet nadirs of <100 ×10(9)/liter. The risk for toxicity did not differ noticeably between 14 and 28 days of therapy and was significantly higher for patients with lower baseline platelet counts. Due to the increased risk of toxicity after longer durations of linezolid therapy and large between-patient variability, close monitoring of patients for development of toxicity is important. Dose individualization based on plasma linezolid concentration profiles and platelet counts should be considered to minimize linezolid-associated thrombocytopenia. Overall, oxazolidinone therapy over 5 to 7 days even at relatively high doses was predicted to be as safe as 10-day therapy of 600 mg linezolid every 12 h.

Case-case-control study on factors associated with vanB vancomycin-resistant and vancomycin-susceptible enterococcal bacteraemia.

BACKGROUND: Enterococci are a major cause of healthcare-associated infection. In Australia, vanB vancomycin-resistant enterococci (VRE) is the predominant genotype. There are limited data on the factors linked to vanB VRE bacteraemia. This study aimed to identify factors associated with vanB VRE bacteraemia, and compare them with those for vancomycin-susceptible enterococci (VSE) bacteraemia. METHODS: A case-case-control study was performed in two tertiary public hospitals in Victoria, Australia. VRE and VSE bacteraemia cases were compared with controls without evidence of enterococcal bacteraemia, but may have had infections due to other pathogens. RESULTS: All VRE isolates had vanB genotype. Factors associated with vanB VRE bacteraemia were urinary catheter use within the last 30 days (OR 2.86, 95% CI 1.09-7.53), an increase in duration of metronidazole therapy (OR 1.65, 95% CI 1.17-2.33), and a higher Chronic Disease Score specific for VRE (OR 1.70, 95% CI 1.05-2.77). Factors linked to VSE bacteraemia were a history of gastrointestinal disease (OR 2.29, 95% CI 1.05-4.99) and an increase in duration of metronidazole therapy (OR 1.23, 95% CI 1.02-1.48). Admission into the haematology/oncology unit was associated with lower odds of VSE bacteraemia (OR 0.08, 95% CI 0.01-0.74). CONCLUSIONS: This is the largest case-case-control study involving vanB VRE bacteraemia. Factors associated with the development of vanB VRE bacteraemia were different to those of VSE bacteraemia.

Genomic analysis of teicoplanin resistance emerging during treatment of vanB vancomycin-resistant Enterococcus faecium infections in solid organ transplant recipients including donor-derived cases.

OBJECTIVES: We noted four cases of apparent in vivo emergence of teicoplanin resistance during failed therapy for initially teicoplanin-susceptible vanB vancomycin-resistant Enterococcus faecium (VREfm) infections in solid organ transplant recipients at our institution over a 12 month period. We investigated if in vivo emergence of resistance had occurred, if transplant-related vancomycin-resistant Enterococcus (VRE) infections had occurred and identified clinical predictors of resistance emergence. METHODS: Whole genome sequencing was performed on nine VREfm isolates for phylogenetic analysis and to identify determinants of teicoplanin resistance. Clinical treatment details were compared with other patients who received teicoplanin for confirmed vanB VRE infections but did not develop resistance during the same year at our institution. RESULTS: A high-resolution, core genome phylogeny was inferred for nine VREfm isolates and confirmed in vivo development of resistance during failed therapy in four cases. Four different non-synonymous single nucleotide polymorphisms (SNPs) were observed in the vanRS genes of teicoplanin-resistant strains compared with the index teicoplanin-susceptible strains, and these SNPs were predicted to confer teicoplanin resistance. VREfm within a cluster of early transplant-related infections were phylogenetically identical at the core genome level, indicating a common source donor. Focus eradication and absence of prosthetic material were characteristics of those patients treated successfully. CONCLUSIONS: Clinicians should be cautious of resistance emerging during teicoplanin therapy for vanB VRE, particularly in immunosuppressed patients or where source control is difficult.

Peripheral intravenous catheter-associated Staphylococcus aureus bacteraemia: more than 5 years of prospective data from two tertiary health services.

OBJECTIVES: To determine the incidence, risk factors for and outcomes of Staphylococcus aureus bacteraemia (SAB) associated with peripheral intravenous catheters (PIVCs). DESIGN, SETTING AND PATIENTS: A review of prospectively collected data from two tertiary health services on all health care-associated SAB episodes occurring in adults aged > 17 2013s from January 2007 to July 2012. MAIN OUTCOME MEASURES: Numbers of health care-associated SAB episodes; device type, location of insertion, device dwell time and outcome at 7 and 30 days for all SAB episodes associated with use of a PIVC; rates of SAB per 10 000 occupied bed-days (OBDs). RESULTS: Overall, 137 of 583 health care-associated-SAB episodes (23.5%) were deemed to be PIVC associated, with an incidence of 0.26/10 000 OBD. The mean dwell time for PIVCs was 3.5 days (range, 0.25-9 days) and 45.2% of SABs occurred in PIVCs with a dwell time ≥ 4 days. Of the PIVC-associated SAB episodes, 39.6% involved PIVCs inserted in the ED, 39.6% involved PIVCs inserted on wards and 20.8% involved PIVCs inserted by the ambulance service. Of the PIVC-associated SABs occurring within 4 days of insertion, 61% were inserted by ED staff or the ambulance service. PIVC-associated SAB were associated with a 30-day all-cause mortality rate of 26.5%. CONCLUSION: PIVC-associated SAB is an under-recognised complication. The high incidences of SAB associated with PIVCs inserted in emergency locations and with prolonged dwell times support recommendations in clinical guidelines for routine removal of PIVCs.

Australian Donation and Transplantation Biobank: A Research Biobank Integrated Within a Deceased Organ and Tissue Donation Program.

We aimed to facilitate the donation of tissue samples for research by establishing a centralized system integrated in the organ donation program for collection, storage, and distribution of samples (the Australian Donation and Transplantation Biobank [ADTB]). Methods: Feasibility of a research biobank integrated within the deceased organ and tissue donation program was assessed. DonateLife Victoria sought consent for ADTB donation after consent was received for organ donation for transplantation from the donor's senior available next of kin. ADTB samples were collected during donation surgery and distributed fresh to researchers or stored for future research. The main outcome measures were ADTB donation rates, ADTB sample collection, ADTB sample use, and to identify ethical considerations. Results: Over 2 y, samples were collected for the ADTB from 69 donors (28% of 249 donors). Samples were obtained from the spleen (n = 59, 86%), colon (n = 57, 83%), ileum (n = 56, 82%), duodenum (n = 55, 80%), blood (n = 55, 80%), bone marrow (n = 55, 80%), skin (n = 54, 78%), mesenteric lymph nodes (n = 56, 81%), liver (n = 21, 30%), lung (n = 29, 42%), and lung-draining lymph node (n = 29, 42%). Heart (n = 20), breast (n = 1), and lower urinary tract (n = 1) samples were obtained in the second year. Five hundred fifty-six samples were used in 19 ethics-approved research projects spanning the fields of immunology, microbiology, oncology, anatomy, physiology, and surgery. Conclusions: The integration of routine deceased donation and transplantation activities with a coordinated system for retrieval and allocation of donor samples for use in a range of research projects is feasible and valuable.

Comparative analysis of the first complete Enterococcus faecium genome.

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.

Forgotten antibiotics: an inventory in Europe, the United States, Canada, and Australia.

In view of the alarming spread of antimicrobial resistance in the absence of new antibiotics, this study aimed at assessing the availability of potentially useful older antibiotics. A survey was performed in 38 countries among experts including hospital pharmacists, microbiologists, and infectious disease specialists in Europe, the United States, Canada, and Australia. An international expert panel selected systemic antibacterial drugs for their potential to treat infections caused by resistant bacteria or their unique value for specific criteria. Twenty-two of the 33 selected antibiotics were available in fewer than 20 of 38 countries. Economic motives were the major cause for discontinuation of marketing of these antibiotics. Fourteen of 33 antibiotics are potentially active against either resistant Gram-positive or Gram-negative bacteria. Urgent measures are then needed to ensure better availability of these antibiotics on a global scale.

Impact of swine influenza and quarantine measures on patients and households during the H1N1/09 pandemic.

OBJECTIVES: To assess the secondary attack rates (SAR) and impact of the 2009 H1N1 epidemic in Melbourne, Victoria, Australia, and the measures implemented to control household transmission. METHODS: Patients with polymerase chain reaction-confirmed influenza A and pandemic H1N1 (pH1N1) were identified from hospital and microbiology laboratory records and asked to take part in a retrospective survey. Information obtained included: the constellation of symptoms, contact history, secondary infection, and household information, including adherence and attitudes towards quarantine measures. RESULTS: The overall SAR of pH1N1 index patients was 30.6%, but a significantly lower SAR was noted with oseltamivir treatment (36.6% vs 22.8%, p < 0.05). The greatest reduction in SAR was observed when index patients aged 0-4 y received oseltamivir (83.3% vs 22.2%, p < 0.01). Quarantine was requested of 65.8% of patients and 92.8% self-reported adhering to recommendations. pH1N1 index patients, the number of median days bed-bound is 2.5 days, being unable or too sick to work for a median of 5.0 days, and lost a median of 7.0 days of work for reasons related to an influenza-like illness. CONCLUSIONS: The pH1N1 influenza pandemic had a significant clinical impact on households. Public health interventions such as oseltamivir treatment of index cases were beneficial in reducing secondary attack rates, whilst quarantine measures were found to have high rates of self-reported compliance, understanding, and acceptability.

Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications.

The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) over the past decade has provided a challenge to diagnostic microbiologists to detect these strains, clinicians treating patients with infections due to these strains, and researchers attempting to understand the resistance mechanisms. Recent data show that these strains have been detected globally and in many cases are associated with glycopeptide treatment failure; however, more rigorous clinical studies are required to clearly define the contribution of hVISA to glycopeptide treatment outcomes. It is now becoming clear that sequential point mutations in key global regulatory genes contribute to the hVISA and VISA phenotypes, which are associated predominately with cell wall thickening and restricted vancomycin access to its site of activity in the division septum; however, the phenotypic features of these strains can vary because the mutations leading to resistance can vary. Interestingly, changes in the staphylococcal surface and expression of agr are likely to impact host-pathogen interactions in hVISA and VISA infections. Given the subtleties of vancomycin susceptibility testing against S. aureus, it is imperative that diagnostic laboratories use well-standardized methods and have a framework for detecting reduced vancomycin susceptibility in S. aureus.

Optimising genomic approaches for identifying vancomycin-resistant Enterococcus faecium transmission in healthcare settings.

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.