Identification of antibiotic consumption targets for the management of Clostridioides difficile infection in hospitals- a threshold logistic modelling approach.

BACKGROUND: This study aims to demonstrate the utility of a threshold logistic approach to identifying thresholds for specific antibiotic use associated with Clostridioides difficile infection (CDI) in an English teaching hospital. METHODS: A combined approach of nonlinear modeling and logistic regression, named threshold logistic, was used to identify thresholds and risk scores in hospital-level antibiotic use associated with hospital-onset, healthcare-associated (HOHA) CDI cases. RESULTS: Using a threshold logistic regression approach, an incidence greater than 0.2645 cases/1000 occupied bed-days (OBD; 85th percentile) was determined as the cutoff rate to define a critical (high) incidence rate of HOHA CDI. Fluoroquinolones and piperacillin-tazobactam were found to have thresholds at 84.8 and 54 defined daily doses (DDD)/1000 OBD, respectively. Analysis of data allowed calculating risk scores for HOHA CDI incidence rates exceeding the 85th percentile, i.e. entering critical incidence level. The threshold-logistic model also facilitated performing 'what-if scenarios' on future values of fluoroquinolones and piperacillin-tazobactam use to understand how HOHA CDI incidence rates may be affected. CONCLUSION: Using threshold logistic analysis, critical incidence levels and antibiotic use targets to control HOHA CDI were determined. Threshold logistic models can be used to inform and enhance the effective design and implementation of antimicrobial stewardship programs.

Expert consensus recommendations for the provision of infective endocarditis services: updated guidance from the Joint British Societies.

Infective endocarditis (IE) remains a difficult condition to diagnose and treat and is an infection of high consequence for patients, causing long hospital stays, life-changing complications and high mortality. A new multidisciplinary, multiprofessional, British Society for Antimicrobial Chemotherapy (BSAC)-ledWorking Party was convened to undertake a focused systematical review of the literature and to update the previous BSAC guidelines relating delivery of services for patients with IE. A scoping exercise identified new questions concerning optimal delivery of care, and the systematic review identified 16 231 papers of which 20 met the inclusion criteria. Recommendations relating to endocarditis teams, infrastructure and support, endocarditis referral processes, patient follow-up and patient information, and governance are made as well as research recommendations. This is a report of a joint Working Party of the BSAC, British Cardiovascular Society, British Heart Valve Society, British Society of Echocardiography, Society of Cardiothoracic Surgeons of Great Britain and Ireland, British Congenital Cardiac Association and British Infection Association.

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression.

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.

Infective endocarditis: acne to zoonoses on the valve, an A to Z perspective.

Cutibacterium acnes (C. acnes), previously known as Propionibacterium acnes, is a rare cause of infective endocarditis (IE). We provide a review of the literature and describe two recent cases from a single centre to provide insight into the various clinical presentations, progression and management of patients with this infection. The primary objective of our review is to highlight the difficulty in the initial assessment of these patients with an aim to improve the time and accuracy of diagnosis and expedite subsequent treatment. There are currently no guidelines in the literature specific to the management of IE caused by C. acnes. Our secondary objectives are to disseminate information about the indolent course of the disease and add to the growing body of evidence around this rare, yet complex, cause of IE.

Use of dalbavancin in infective endocarditis: a case series.

BACKGROUND: Infective endocarditis, typically caused by Gram-positive organisms such as viridans group streptococci and Staphylococcus aureus, is associated with high mortality and morbidity and requires aggressive, prolonged antimicrobial treatment and sometimes surgery. Dalbavancin, a lipoglycopeptide active against Gram-positive pathogens, has a long half-life, which allows IV treatment as one dose or two doses with a prolonged interval, offering personalized treatment for complex psychosocial situations or facilitating early discharge. In the absence of randomized controlled trials in infective endocarditis, current evidence derives from real-world case series involving off-licence use. The Austrian Society for Infectious Disease and Tropical Medicine includes dalbavancin as an option for infective endocarditis. OBJECTIVES: This retrospective case series reports use of dalbavancin in a small cohort of patients with infective endocarditis treated at Lancashire Cardiac Centre, Blackpool Teaching Hospitals Foundation Trust, UK. RESULTS: The pharmacy database included 11 patients in whom dalbavancin was used to address either complex psychosocial circumstances or the need for early discharge. The endocarditis multidisciplinary team selected dalbavancin from available treatment options. Structures affected by infective endocarditis included aortic, mitral and tricuspid valves; aortic composite grafts; implantable cardioverter defibrillator leads; and prosthetic aortic valves. Eight patients underwent surgery; three were managed conservatively with antibiotics. Dalbavancin was curative in all but one patient, whose signs and symptoms of infection improved. No patients developed adverse reactions. CONCLUSIONS: Dalbavancin is an alternative treatment option at hospital discharge when conventional antibiotics may not be suitable due to complex psychosocial issues or early discharge is required.

Rapid systematic review of neonatal COVID-19 including a case of presumed vertical transmission.

OBJECTIVE: To carry out a systematic review of the available studies on COVID-19 (coronavirus disease 2019) in neonates seen globally since the onset of the COVID-19 global pandemic in 2020. The paper also describes a premature baby with reverse transcription (RT)-PCR-positive COVID-19 seen at the Blackpool Teaching Hospitals NHS Foundation Trust, UK. DESIGN: We conducted a multifaceted search of the Cumulative Index to Nursing and Allied Health Literature, Embase, Medline and PubMed from 1 December 2019 to 12 May 2020 to harvest articles from medical journals and publications reporting cases of COVID-19 in neonates from anywhere in the world. Additional searches were also done so as not to miss any important publications. Write-up was in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, the protocol for the review was registered with International Prospective Register of Systematic Reviews (PROSPERO), and risk of bias was analysed with the Newcastle-Ottawa tool. Additionally, the preterm neonate with COVID-19 from our hospital is also reported. RESULTS: The systematic review has revealed eight studies where neonates have been described to have confirmed COVID-19, with low risk of bias. Of the 10 reported cases elsewhere, only three are likely to be vertically transmitted, while seven occurred in the postperinatal period and are likely to have been postnatally acquired. All neonates had a mild course, recovered fully and were negative on retesting. Our case of COVID-19 in a 32-week premature baby from the UK was delivered by emergency caesarean section, with the mother wearing a face mask and the family having no contact with the neonate, suggesting vertical transmission. On day 33, the neonate was asymptomatic but was still RT-PCR-positive on nasopharyngeal airway swab. CONCLUSIONS: Neonatal infection is uncommon, with only two previously reported cases likely to be of vertical transmission. The case we report is still RT-PCR-positive on day 28 and is asymptomatic. Ongoing research is needed to ascertain the epidemiology of COVID-19 in neonates.

Opportunities for antimicrobial stewardship in patients with acute bacterial skin and skin structure infections who are unsuitable for beta-lactam antibiotics: a multicenter prospective observational study.

PURPOSE: The objective of this prospective, observational study was to describe the treatment, severity assessment and healthcare resources required for management of patients with acute bacterial skin and skin structure infections who were unsuitable for beta-lactam antibiotic treatments. METHODS: Patients were enrolled across five secondary care National Health Service hospitals. Eligible patients had a diagnosis of acute bacterial skin and skin structure infection and were considered unsuitable for beta-lactam antibiotics (e.g. confirmed/suspected methicillin-resistant Staphylococcus aureus, beta-lactam allergy). Data regarding diagnosis, severity of the infection, antibiotic treatment and patient management were collected. RESULTS: 145 patients with acute bacterial skin and skin structure infection were included; 79% (n = 115) patients received greater than two antibiotic regimens; median length of the first antibiotic regimen was 2 days (interquartile range of 1-5); median time to switch from intravenous to oral antibiotics was 4 days (interquartile range of 3-8, n = 72/107); 25% (n = 10/40) patients with Eron class 1 infection had systemic inflammatory response syndrome, suggesting they were misclassified. A higher proportion of patients with systemic inflammatory response syndrome received treatment in an inpatient setting, and their length of stay was prolonged in comparison with patients without systemic inflammatory response syndrome. CONCLUSION: There exists an urgent need for more focused antimicrobial stewardship strategies and tools for standardised clinical assessment of acute bacterial skin and skin structure infection severity in patients who are unsuitable for beta-lactam antibiotics. This will lead to optimised antimicrobial treatment strategies and ensure effective healthcare resource utilisation.

Updated good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) in adults and children in the UK.

UK good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) were published in 2012 and 2015 for adult and paediatric patients, respectively. Here we update the initial good practice recommendations in a combined document based on a further review of the OPAT literature and an extensive consultation process. As with the previous good practice recommendations, these updated recommendations are intended to provide pragmatic guidance for new and established OPAT services across a range of settings and to act as a set of quality indicators for service evaluation and quality improvement.

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia: the ARREST RCT.

BACKGROUND: Staphylococcus aureus bacteraemia is a common and frequently fatal infection. Adjunctive rifampicin may enhance early S. aureus killing, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. OBJECTIVES: To determine whether or not adjunctive rifampicin reduces bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. Secondary objectives included evaluating the impact of rifampicin on all-cause mortality, clinically defined failure/recurrence or death, toxicity, resistance emergence, and duration of bacteraemia; and assessing the cost-effectiveness of rifampicin. DESIGN: Parallel-group, randomised (1 : 1), blinded, placebo-controlled multicentre trial. SETTING: UK NHS trust hospitals. PARTICIPANTS: Adult inpatients (≥ 18 years) with meticillin-resistant or susceptible S. aureus grown from one or more blood cultures, who had received < 96 hours of antibiotic therapy for the current infection, and without contraindications to rifampicin. INTERVENTIONS: Adjunctive rifampicin (600-900 mg/day, oral or intravenous) or placebo for 14 days in addition to standard antibiotic therapy. Investigators and patients were blinded to trial treatment. Follow-up was for 12 weeks (assessments at 3, 7, 10 and 14 days, weekly until discharge and final assessment at 12 weeks post randomisation). MAIN OUTCOME MEASURES: The primary outcome was all-cause bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. RESULTS: Between December 2012 and October 2016, 758 eligible participants from 29 UK hospitals were randomised: 370 to rifampicin and 388 to placebo. The median age was 65 years [interquartile range (IQR) 50-76 years]. A total of 485 (64.0%) infections were community acquired and 132 (17.4%) were nosocomial; 47 (6.2%) were caused by meticillin-resistant S. aureus. A total of 301 (39.7%) participants had an initial deep infection focus. Standard antibiotics were given for a median of 29 days (IQR 18-45 days) and 619 (81.7%) participants received flucloxacillin. By 12 weeks, 62 out of 370 (16.8%) patients taking rifampicin versus 71 out of 388 (18.3%) participants taking the placebo experienced bacteriological (microbiologically confirmed) failure/recurrence or died [absolute risk difference -1.4%, 95% confidence interval (CI) -7.0% to 4.3%; hazard ratio 0.96, 95% CI 0.68 to 1.35; p = 0.81]. There were 4 (1.1%) and 5 (1.3%) bacteriological failures (p = 0.82) in the rifampicin and placebo groups, respectively. There were 3 (0.8%) versus 16 (4.1%) bacteriological recurrences (p = 0.01), and 55 (14.9%) versus 50 (12.9%) deaths without bacteriological failure/recurrence (p = 0.30) in the rifampicin and placebo groups, respectively. Over 12 weeks, there was no evidence of differences in clinically defined failure/recurrence/death (p = 0.84), all-cause mortality (p = 0.60), serious (p = 0.17) or grade 3/4 (p = 0.36) adverse events (AEs). However, 63 (17.0%) participants in the rifampicin group versus 39 (10.1%) participants in the placebo group experienced antibiotic or trial drug-modifying AEs (p = 0.004), and 24 (6.5%) participants in the rifampicin group versus 6 (1.5%) participants in the placebo group experienced drug-interactions (p = 0.0005). Evaluation of the costs and health-related quality-of-life impacts revealed that an episode of S. aureus bacteraemia costs an average of £12,197 over 12 weeks. Rifampicin was estimated to save 10% of episode costs (p = 0.14). After adjustment, the effect of rifampicin on total quality-adjusted life-years (QALYs) was positive (0.004 QALYs), but not statistically significant (standard error 0.004 QALYs). CONCLUSIONS: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S. aureus bacteraemia. FUTURE WORK: Given the substantial mortality, other antibiotic combinations or improved source management should be investigated. TRIAL REGISTRATIONS: Current Controlled Trials ISRCTN37666216, EudraCT 2012-000344-10 and Clinical Trials Authorisation 00316/0243/001. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 59. See the NIHR Journals Library website for further project information.

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment.

Effectiveness and safety of daptomycin in patients with infective endocarditis undergoing heart valve replacement: a subgroup analysis from real-world data.

BACKGROUND: European Cubicin® Outcomes Registry and Experience (EU-CORE) was a retrospective, non-interventional, multicenter registry that collected real-world clinical outcomes following daptomycin use for the treatment of Gram-positive infections. EU-CORE data from patients with infective endocarditis (IE) who underwent heart valve replacement were analysed. METHODS: Clinical outcomes were assessed as success (cured or improved), failure, or non-evaluable. Adverse events (AEs) were recorded for up to 30 days after daptomycin treatment. RESULTS: Of 610 patients with IE, 198 [32.5%; left-sided IE (LIE), 166 (83.8%); right-sided IE (RIE), 21 (10.6%); both LIE and RIE, 11 (5.6%)] underwent heart valve replacement. Other than cardiovascular disease, renal disease (18.2%), sepsis (16.2%), and diabetes mellitus (15.2%) were the most significant underlying diseases. Major pathogens in patients with positive culture results (68.0%) were Staphylococcus aureus [36.8%; methicillin-resistant S. aureus (MRSA), 12.8%] and coagulase-negative staphylococci (CoNS; 31.6%). Daptomycin treatment [median duration (range), 21 days (1-112)] resulted in high clinical success in patients with S. aureus (88.4%; MRSA, 80.0%) and CoNS (81.1%) infections, with an overall success rate of 83.3%. Clinical success rate was high (90.0%) in patients who received daptomycin dose >6 mg/kg/day. Overall clinical success rate in patients followed for up to 2 years was 90.7%. AEs and serious AEs possibly related to daptomycin were reported in 6 (3.0%) and 4 (2.0%) patients, respectively. CONCLUSIONS: Daptomycin treatment was effective and well tolerated with a sustained response in patients with IE who underwent heart valve surgery. A trend towards better clinical outcomes was observed with higher daptomycin doses.

Daptomycin for the Treatment of Infective Endocarditis: Results from European Cubicin(®) Outcomes Registry and Experience (EU-CORE).

INTRODUCTION: The European Cubicin(®) Outcomes Registry and Experience (EU-CORE(SM)) was a retrospective, non-interventional, multicenter study which evaluated the safety and effectiveness of daptomycin therapy in patients with Gram-positive infections including infective endocarditis (IE). METHODS: Data from the EU-CORE registry were collected for patients with IE who had received at least one dose of daptomycin between January 2006 and April 2012, across 18 countries in Europe (12), Latin America (5) and Asia (1). Clinical outcomes were assessed as success (cured or improved), failure or non-evaluable. Adverse events (AEs) were recorded during treatment and for up to 30 days post-treatment; follow-up data were collected for 2 years. RESULTS: Of 6075 patients included in the EU-CORE registry, 610 were diagnosed with IE as primary infection; 149 (24.4%) right-sided IE (RIE), 414 (67.9%) left-sided IE (LIE), and 47 (7.7%) with both right- and left-sided IE (BRLIE). Overall clinical success was achieved in 80.0% of patients (RIE 88.6%, LIE 76.6% and BRLIE 82.9%). Success rates for methicillin-resistant Staphylococcus aureus (MRSA) infections were 90.9%, 71.7% and 66.6% in patients with RIE, LIE and BRLIE, respectively. The overall sustained clinical success rate in patients followed for up to 2 years was 86.7% (RIE 93.5%, LIE 88.3% and BRLIE 77.8%). AEs deemed possibly related to daptomycin in the investigator's opinion were reported in 2 (1.3%) RIE, 18 (4.3%) LIE and 1 (2.1%) BRLIE patients. There were 11 (1.8%) patients (2 with RIE, 8 with LIE and 1 with BRLIE) with AEs of creatine phosphokinase elevation reported as possibly related to daptomycin. CONCLUSION: Data from this real-world clinical setting showed that daptomycin was well tolerated and effective for the treatment of LIE and BRLIE in addition to RIE caused by Gram-positive bacteria, including MRSA. Two-year follow-up data showed that a high proportion of patients had a sustained response.

Guidelines for the diagnosis, prevention and management of implantable cardiac electronic device infection. Report of a joint Working Party project on behalf of the British Society for Antimicrobial Chemotherapy (BSAC, host organization), British Heart Rhythm Society (BHRS), British Cardiovascular Society (BCS), British Heart Valve Society (BHVS) and British Society for Echocardiography (BSE).

Infections related to implantable cardiac electronic devices (ICEDs), including pacemakers, implantable cardiac defibrillators and cardiac resynchronization therapy devices, are increasing in incidence in the USA and are likely to increase in the UK, because more devices are being implanted. These devices have both intravascular and extravascular components and infection can involve the generator, device leads and native cardiac structures or various combinations. ICED infections can be life-threatening, particularly when associated with endocardial infection, and all-cause mortality of up to 35% has been reported. Like infective endocarditis, ICED infections can be difficult to diagnose and manage. This guideline aims to (i) improve the quality of care provided to patients with ICEDs, (ii) provide an educational resource for all relevant healthcare professionals, (iii) encourage a multidisciplinary approach to ICED infection management, (iv) promote a standardized approach to the diagnosis, management, surveillance and prevention of ICED infection through pragmatic evidence-rated recommendations, and (v) advise on future research projects/audit. The guideline is intended to assist in the clinical care of patients with suspected or confirmed ICED infection in the UK, to inform local infection prevention and treatment policies and guidelines and to be used in the development of educational and training material by the relevant professional societies. The questions covered by the guideline are presented at the beginning of each section.

Legionella pneumonia cases over a five-year period: a descriptive, retrospective study of outcomes in a UK district hospital.

As the recent outbreaks in Edinburgh and Camarthen, UK, have shown, Legionella pneumonia (LP) remains a significant public health problem, which is not only confined to those who have travelled abroad. In both outbreaks and sporadic cases, diagnosis can go unrecognised. We reviewed the demographics, comorbidities, diagnosis, treatment and clinical outcome of LP cases over five years in a district general hospital in northwest England. Over half of LP cases were UK acquired and 'classic' clinical features were common. Clinical criteria for diagnosing LP were confirmed, but few sputum samples were sent to reference laboratories, limiting further essential epidemiological mapping of UK cases. Following current UK community-acquired pneumonia guidance would have missed nearly one quarter of LP cases in our series, potentially leading to further morbidity and mortality.

Daptomycin for the treatment of infective endocarditis: results from a European registry.

OBJECTIVES: Infective endocarditis (IE) is a complex infection associated with high mortality. Daptomycin, a cyclic lipopeptide antibiotic highly active against Gram-positive bacteria, has recently been incorporated into IE treatment guidelines. This retrospective analysis provides insights into the use of daptomycin in IE in the European Cubicin(®) Outcomes Registry Experience (EU-CORE(SM)) between 2006 and 2010. PATIENTS AND METHODS: Three hundred and seventy-eight (10%) of 3621 enrolled patients received daptomycin for treatment of IE. Two hundred and fifty-nine (69%) had left-sided IE (LIE) and 182 patients (48%) underwent concomitant surgery. RESULTS: Staphylococcus aureus was the most frequently identified pathogen (n=92; methicillin susceptible, n=50) and daptomycin was used empirically in 134 patients. Among cases of second-line therapy (n=312), the most common reason for switching to daptomycin was failure of the previous regimen (including glycopeptides and penicillins). Daptomycin was administered at 6 mg/kg in 224 patients and at ≥ 8 mg/kg in 72 patients. Clinical success rates were 80% overall, 91% for right-sided IE (RIE) and 76% for LIE, with similar rates seen for infections caused by methicillin-susceptible S. aureus (84%) and methicillin-resistant S. aureus (81%). The clinical success rate in patients treated with ≥ 8 mg/kg daptomycin was 90% [n=72 (RIE, 91%; LIE, 89%)]. No new safety signals were observed. CONCLUSIONS: In patients with IE registered in EU-CORE, daptomycin was most frequently used as second-line treatment after treatment failure. The majority of patients had LIE and most commonly received daptomycin for the treatment of staphylococcal infections. Clinical success was high in this difficult-to-treat population. The role of doses ≥ 8 mg/kg per day in the empirical treatment of IE deserves further investigation.

Salvage therapy with topical antifungal for Aspergillus fumigatus empyema complicating extrapleural pneumonectomy.

We describe an unusual case of Aspergillus fumigatus empyema and bronchopleural fistulae after extrapleural pneumonectomy (EPP) and chemoradiotherapy (CRT), which was treated successfully under salvage conditions with debridement, an innovative topical antifungal application and supplemented systemic antifungal therapy and which went on for a definitive surgical procedure. Combinations of CRT and EPP have been recommended in a select group of patients with malignant mesothelioma. Irrespective of the combination, EPP is associated with mortality in the range of 4-15% and a complication rate as high as 62%.

Anaphylaxis to chlorhexidine-coated central venous catheters: a case series and review of the literature.

BACKGROUND: Anaphylactic reactions to chlorhexidine are rare but are being reported increasingly in association with a variety of products. METHODS: We report three cases of anaphylaxis to chlorhexidine in patients presenting for cardiac surgery. RESULTS: In each case, anaphylaxis was precipitated by the insertion of a central venous catheter impregnated with chlorhexidine acetate. Subsequent investigations confirmed chlorhexidine as the causal agent. CONCLUSION: Extensive use of chlorhexidine to reduce hospital-acquired infections has the potential to sensitize a small proportion of patients, leading to life-threatening anaphylaxis on subsequent exposure.