Objectives: Tigecycline has shown in vitro activity against Acinetobacter baumannii. Yet, published clinical experience with tigecycline use outside clinical trials is lacking. We describe, for the ...first time, bloodstream infection caused by tigecycline-non-susceptible A. baumannii occurring in patients receiving tigecycline for other indications. The possible mechanisms of resistance and pharmacokinetic limitations of the drug are addressed. Methods: The clinical records of involved patients were systematically reviewed. Tigecycline susceptibility testing was initially performed using the Etest method and confirmed by agar dilution. Involved isolates underwent PFGE and exposure to phenyl-arginine-β-naphthylamide (PAβN), an efflux pump inhibitor. Results: Two patients developed A. baumannii bloodstream infection while receiving tigecycline. Tigecycline was administered for other indications for 9 and 16 days, respectively, before the onset of A. baumannii infection. Patient 1 died of overwhelming A. baumannii infection and Patient 2 recovered after a change in antibiotic therapy. The MICs of tigecycline were 4 and 16 mg/L, respectively. Both isolates had a multidrug-resistant phenotype and were genotypically unrelated. After exposure to PAβN, the MICs reduced to 1 and 4 mg/L, respectively. Conclusions: To our knowledge, this is the first clinical description of bloodstream infection caused by tigecycline-non-susceptible A. baumannii. Such resistance appears to be at least partly attributable to an efflux pump mechanism. Given the reported low serum tigecycline levels, we urge caution when using this drug for treatment of A. baumannii bloodstream infection.
To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI).
Prospective studies, randomized trials or registered protocols ...comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process.
Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed.
These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centred clinical outcomes.
Few studies have used molecular epidemiological methods to study transmission links to clinical isolates in intensive care units. Ninety-four multidrug-resistant organisms (MDROs) cultured from ...routine specimens from intensive care unit (ICU) patients over 13 weeks were stored (11 meticillin-resistant Staphylococcus aureus (MRSA), two vancomycin-resistant enterococci and 81 Gram-negative bacteria). Medical staff personal mobile phones, departmental phones, and ICU keyboards were swabbed and cultured for MDROs; MRSA was isolated from two phones. Environmental and patient isolates of the same genus were selected for whole genome sequencing. On whole genome sequencing, the mobile phone isolates had a pairwise single nucleotide polymorphism (SNP) distance of 183. However, >15,000 core genome SNPs separated the mobile phone and clinical isolates. In a low-endemic setting, mobile phones and keyboards appear unlikely to contribute to hospital-acquired MDROs.
Healthcare-associated infections (HAIs) and antimicrobial use (AMU) are important drivers of antimicrobial resistance, yet there is minimal data from the Pacific region. We sought to determine the ...point prevalence of HAIs and AMU at Fiji's largest hospital, the Colonial War Memorial Hospital (CWMH) in Suva. A secondary aim was to evaluate the performance of European Centre for Diseases Prevention and Control (ECDC) HAI criteria in a resource-limited setting.
We conducted a point prevalence survey of HAIs and AMU at CWMH in October 2019. Survey methodology was adapted from the ECDC protocol. To evaluate the suitability of ECDC HAI criteria in our setting, we augmented the survey to identify patients with a clinician diagnosis of a HAI where diagnostic testing criteria were not met. We also assessed infection prevention and control (IPC) infrastructure on each ward.
We surveyed 343 patients, with median (interquartile range) age 30 years (16-53), predominantly admitted under obstetrics/gynaecology (94, 27.4%) or paediatrics (83, 24.2%). Thirty patients had one or more HAIs, a point prevalence of 8.7% (95% CI 6.0% to 12.3%). The most common HAIs were surgical site infections (n = 13), skin and soft tissue infections (7) and neonatal clinical sepsis (6). Two additional patients were identified with physician-diagnosed HAIs that failed to meet ECDC criteria due to insufficient investigations. 206 (60.1%) patients were receiving at least one antimicrobial. Of the 325 antimicrobial prescriptions, the most common agents were ampicillin (58/325, 17.8%), cloxacillin (55/325, 16.9%) and metronidazole (53/325, 16.3%). Use of broad-spectrum agents such as piperacillin/tazobactam (n = 6) and meropenem (1) was low. The majority of prescriptions for surgical prophylaxis were for more than 1 day (45/76, 59.2%). Although the number of handwashing basins throughout the hospital exceeded World Health Organization recommendations, availability of alcohol-based handrub was limited and most concentrated within high-risk wards.
The prevalence of HAIs in Fiji was similar to neighbouring high-income countries, but may have been reduced by the high proportion of paediatric and obstetrics patients, or by lower rates of inpatient investigations. AMU was very high, with duration of surgical prophylaxis an important target for future antimicrobial stewardship initiatives.
The utility of peptide nucleic acid fluorescence in situ hybridization (PNA FISH) for the detection of Acinetobacter spp. and Pseudomonas aeruginosa was evaluated on broth suspensions and spiked ...blood cultures of ATCC strains and clinical isolates with select gram-negative rods. After testing 60 clinical isolates, PNA FISH had a sensitivity and specificity of 100% and 100%, respectively, for Acinetobacter spp. and 100% and 95%, respectively, for P. aeruginosa. PNA FISH was able to detect both pathogens simultaneously and directly from spiked blood cultures.
Objectives: To assess whether a continuous infusion of amphotericin B (CI-AmB) is less nephrotoxic than a 4 h infusion in haematology patients with fever and neutropenia, including bone-marrow ...transplant recipients. Efficacy was assessed as a secondary end-point. Patients and methods: We conducted a retrospective cohort study over a 2 year period. A total of 1073 haematology admissions were reviewed (98.3% complete) and 81 admissions were eligible for study entry; 39 received CI-AmB and 42 a 4 h infusion of AmB. Results: Renal impairment occurred significantly less frequently with CI-AmB compared with a 4 h infusion of AmB 10% versus 45%, respectively, odds ratio (OR) 0.14; 95% confidence interval (CI) 0.04–0.5, P<0.001. The difference was maintained among allogeneic transplant recipients (P=0.007) and patients receiving concurrent nephrotoxic drugs (P<0.001). An AmB infusion rate of <0.08 mg/kg/h was associated with a significant reduction in renal impairment (P<0.001). A difference in survival was observed between the continuous and 4 h infusion of AmB (95% versus 79%, respectively, OR 5.1; 95% CI 1.02–25.1, P=0.03). Conclusions: CI-AmB appears to be significantly less nephrotoxic than 4 h infusion AmB in haematology patients with fever and neutropenia—including high-risk bone-marrow transplant recipients—without increasing mortality. An AmB infusion rate of <0.08 mg/kg/h appears to be a safe threshold, associated with reduced renal impairment.
A multicentre, case-control study was conducted to assess risk factors and patient outcomes of bacteraemia caused by Enterobacteriaceae producing extended-spectrum β-lactamases (ESBLs) and Klebsiella ...pneumoniae carbapenemases (KPCs). One hundred and five and 20 patients with bacteraemia caused by ESBL-producing and KPC-producing organisms were matched to controls who had bacteraemia caused by non-ESBL/KPC-producing organisms, respectively. Independent risk factors for ESBL production included admission from a nursing home (OR 4.64; 95% CI 2.64–8.16), chronic renal failure (OR 2.09; 95% CI 1.11–3.92), the presence of a gastrostomy tube (OR 3.36; 95% CI 1.38–8.18), length of hospital stay before infection (OR 1.02; 95% CI 1.01–1.03), transplant receipt (OR 2.48; 95% CI 1.24–4.95), and receipt of antibiotics with Gram-negative activity in the preceding 30 days (OR 1.76; 95% CI 1.00–3.08). Twenty-eight-day crude mortality rates for patients infected with ESBL-producing or KPC-producing organisms and controls were 29.1% (34/117) and 19.5% (53/272), respectively (OR 1.70; 95% CI 1.04–2.80). On multivariate analysis, inadequate empirical therapy (OR 2.26; 95% CI 1.18–4.34), onset of bacteraemia while in the intensive-care unit (OR 2.74; 95% CI 1.47–5.11), Apache II score (OR 1.17; 95% CI 1.12–1.23) and malignancy (OR 2.66; 95% CI 1.31–5.41) were independent risk factors for mortality. CTX-M was the most common ESBL type in Escherichia coli, whereas SHV predominated in Klebsiella spp. and Enterobacter spp.
Eight patients with invasive bacteremic community-acquired methicillin-resistant Staphylococcus aureus infection in southeast Queensland, Australia, are reported. One patient died of septic shock. ...Haematogenous seeding to lungs, bone, and other sites was common. All isolates carried the virulence factor Panton-Valentine leukocidin and were either the southwest Pacific clone or the newly described Queensland clone. Clinicians should consider community-acquired methicillin-resistant Staphylococcus aureus infection in any patient presenting to hospital with severe staphylococcal sepsis or pneumonia.
: Aim. Transplant recipients are at risk for hospital‐acquired infections (HAIs), including those caused by Pseudomonas aeruginosa. Of all HAIs, bloodstream infection (BSI) remains one of the most ...life‐threatening.
Methods. Over a 10‐year period, we studied 503 patients, including 149 transplant recipients, with pseudomonal BSI from the University of Pittsburgh Medical Center. Trends in antimicrobial susceptibility, risk factors for multidrug resistance (MDR), and outcomes were compared between transplant and non‐transplant patients.
Results. Resistance to all antibiotic classes was significantly greater in pseudomonal blood culture isolates from transplant compared with non‐transplant patients (P<0.001). Of isolates from transplant recipients (n=207), 43% were MDR, compared with 18% of isolates from non‐transplant patients (n=391) (odds ratio OR 3.47; 95% confidence interval CI 2.34–5.14, P<0.001). Among all patients, independent risk factors for MDR P. aeruginosa BSI included previous transplantation (OR 2.38; 95% CI 1.51–3.76, P<0.001), hospital‐acquired BSI (OR 2.41; 95% CI 1.39–4.18, P=0.002), and prior intensive care unit (ICU) admission (OR 2.04; 95% CI 1.15–3.63, P=0.015). Mortality among transplant recipients was 42%, compared with 32% in non‐transplant patients (OR 1.55; 95% CI 0.87–2.76, P=0.108). For transplant recipients, onset of BSI in the ICU was the only independent predictor of mortality (OR 8.00; 95% CI 1.71–37.42, P=0.008).
Conclusions. Transplant recipients are at greater risk of MDR P. aeruginosa BSI, with an appreciable mortality. Future management must concentrate on the implementation of effective preventative strategies.
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