Fungal infections after liver transplantation: outcomes and risk factors revisited in the MELD era.

Antifungal prophylaxis is recommended in high-risk patients, but risk criteria remain unclear and the predictive value of Model of End-Stage Liver Disease (MELD) score is unknown. In a retrospective, single-center analysis of 667 liver transplants, potential risk factors for fungal infection were assessed, including MELD score. Antifungal prophylaxis was administered in 198 patients (29.4%). During follow-up (mean 43.6 ± 29.6 months), 263 patients (39.4%) developed ≥ 1 episode of fungal infection, and 187 (28.0%) patients developed a probable or proven invasive fungal infection requiring systemic antifungal treatment. Patients receiving antifungal prophylaxis had a lower incidence of fungal infection (29.8% vs. 43.5% without prophylaxis, p < 0.001) and invasive fungal infection (17.7% vs. 32.4%, p < 0.001). One-yr patient survival was 91%, 85% and 69%, respectively, in patients with no fungal infection, fungal colonization and treated invasive fungal infection (p < 0.001); graft survival was 88%, 85% and 66% (p < 0.001). Multivariate analysis indicated that MELD score of 20-30 or ≥ 30 was associated with a 2.0-fold or 4.3-fold increase in relative risk of fungal infection, respectively, and a 2.1-fold or 3.1-fold increase in relative risk of invasive fungal infection. In conclusion, liver transplant patients with a MELD score ≥ 20, and particularly patients with a score ≥ 30, are candidates for antifungal prophylaxis.

Outcomes associated with amphotericin B lipid complex (ABLC) prophylaxis in high-risk liver transplant patients.

Antifungal prophylaxis with liposomal amphotericin B in high-risk liver transplant recipients is recommended, but experience with amphotericin B lipid complex (ABLC, Abelcet(®)) in this setting is limited. Data from 615 liver transplants performed during 1999-2005 were analyzed retrospectively. High-risk patients (n = 146) received a mean cumulative ABLC dose of 955 ± 609 mg (mean duration of 23.3 ± 11.9 days). Low-risk patients (n = 469) received no prophylaxis. During a mean follow-up of 43.8 ± 29.2 months, fungal infections occurred in 32.2% of ABLC patients versus 43.5% of non-prophylaxis patients (P = 0.015). The overall rate of invasive fungal infection was 12.3% in the ABLC group versus 15.6% in the non-prophylaxis patients (P = 0.34). Any Candida infection (ABLC 29.5%, non-prophylaxis 41.2%, P = 0.011), probable or proven invasive Candida infection requiring systemic antifungal treatment (ABLC 18.5%, non-prophylaxis 32.4%, P = 0.001) and invasive abdominal candidiasis during the first 3 months (ABLC 4.1%, non-prophylaxis 9.2%, P = 0.049) were significantly less frequent in the ABLC group. There was no significant difference between groups in the incidence of Aspergillus infections. The ABLC group showed no evidence of nephrotoxicity. In conclusion, the marked and significant differences in infection rates and requirement for systemic treatment in this large population suggest that targeted use of low-dose ABLC therapy to high-risk patients is a valid prophylactic strategy following liver transplantation.

A Case of Phage Therapy against Pandrug-Resistant Achromobacter xylosoxidans in a 12-Year-Old Lung-Transplanted Cystic Fibrosis Patient.

Bacteriophages are a promising therapeutic strategy among cystic fibrosis and lung-transplanted patients, considering the high frequency of colonization/infection caused by pandrug-resistant bacteria. However, little clinical data are available regarding the use of phages for infections with Achromobacter xylosoxidans. A 12-year-old lung-transplanted cystic fibrosis patient received two rounds of phage therapy because of persistent lung infection with pandrug-resistant A. xylosoxidans. Clinical tolerance was perfect, but initial bronchoalveolar lavage (BAL) still grew A. xylosoxidans. The patient's respiratory condition slowly improved and oxygen therapy was stopped. Low-grade airway colonization by A. xylosoxidans persisted for months before samples turned negative. No re-colonisation occurred more than two years after phage therapy was performed and imipenem treatment was stopped. Whole genome sequencing indicated that the eight A. xylosoxidans isolates, collected during phage therapy, belonged to four delineated strains, whereby one had a stop mutation in a gene for a phage receptor. The dynamics of lung colonisation were documented by means of strain-specific qPCRs on different BALs. We report the first case of phage therapy for A. xylosoxidans lung infection in a lung-transplanted patient. The dynamics of airway colonization was more complex than deduced from bacterial culture, involving phage susceptible as well as phage resistant strains.

Unexpected diagnosis of COVID-19-associated disorders by SARS-CoV-2-specific serology.

Facing the ongoing pandemic caused by SARS-CoV-2, there is an urgent need for serological assays identifying individuals with on-going infection as well as past coronavirus infectious disease 2019 (COVID-19). We herein evaluated the analytical performances of the CE IVD-labeled Abbott SARS-CoV-2 IgG assay (Des Plaines, IL, USA) carried out with the automated Abbott Architect™ i2000 platform at Hôpital Européen Georges Pompidou, Paris, France, using serum sample panels obtained from health-workers with COVID-19 history confirmed by positive nucleic acid amplification-based diagnosis and from patients randomly selected for whom serum samples were collected before the COVID-19 epidemic. The Abbott SARS-CoV-2 IgG assay showed sensitivity of 94 % and specificity of 100 %, demonstrating high analytical performances allowing convenient management of suspected on-going and past-infections. In addition, the SARS-CoV-2 IgG positivity rates were compared in COVID-19 positive and COVID-19 free areas from our hospital. Thus, the frequency of SARS-CoV-2-specific IgG was around 10-fold higher in COVID-19 areas than COVID-19 free areas (75 % versus 8%; P < 0.001). Interestingly, several inpatients hospitalized in COVID-19 free areas suffering from a wide range of unexplained clinical features including cardiac, vascular, renal, metabolic and infectious disorders, were unexpectedly found seropositive for SARS-CoV-2 IgG by systematic routine serology, suggesting possible causal involvement of SARS-CoV-2 infection. Taken together, these observations highlight the potential interest of SARS-CoV-2-specific serology in the context of COVID-19 epidemic, especially to assess past SARS-CoV-2 infection as well as possible unexpected COVID-19-associated disorders.

Individual decontamination measures reduce by two the incidence of surgical site infections in spinal surgery.

BACKGROUND: In spinal surgery, incidence of surgical site infections (SSI) is estimated between 1 and 10%. It results in increased morbidity, mortality and cost of management. Individual Staphylococcus aureus (SA) decolonization has already proved efficiency to prevent those events in various surgical domains. The aim of this study was to evaluate a strategy of prevention of SSI and in particular the decolonization of the nasal carriage of SA by a protocol with Mupirocin application. METHODS: We conducted a bicentric observational study on 5314 spinal surgery patients over a seven-year period. In both center, we compared periods before and after implementation of two measures: modification of antibioprophylaxis and staphylococcus decolonization. Homogeneity of the different samples of patients was assessed through measure of individual and surgical variables. We measured monthly incidence of SSI and evaluated its evolution in order to assess efficiency of these interventions. RESULTS: The incidence of SSI decreased by half, from 7.3% to 3% at the Beaujon Hospital and from 8.3% to 3.9% at the Georges-Pompidou European Hospital (GPEH). We do not observe any significant decrease of SA rate in these SSI. CONCLUSION: We believe that Staphylococcus aureus decolonization should be recommended in spinal surgery, and should be combined with an overall improvement of the quality of care.

Campylobacter bacteremia: clinical features and factors associated with fatal outcome.

BACKGROUND: Campylobacter bacteremia is uncommon. The influence of underlying conditions and of the impact of antibiotics on infection outcome are not known. METHODS: From January 2000 through December 2004, 183 episodes of Campylobacter bacteremia were identified in 23 hospitals in the Paris, France, area. The medical records were reviewed. Characteristics of bacteremia due to Campylobacter fetus and to other Campylobacter species were compared. Logistic regression analysis was performed to identify risk factors for fatal outcome within 30 days. RESULTS: Most affected patients were elderly or immunocompromised. C. fetus was the most commonly identified species (in 53% of patients). The main underlying conditions were liver disease (39%) and cancer (38%). The main clinical manifestations were diarrhea (33%) and skin infection (16%). Twenty-seven patients (15%) died within 30 days. Compared with patients with bacteremia due to other Campylobacter species, patients with C. fetus bacteremia were older (mean age, 69.5 years vs. 55.6 years; P = .001) and were more likely to have cellulitis (19% vs. 7%; P = .03), endovascular infection (13% vs. 1%; P = .007), or infection associated with a medical device (7% vs. 0%; P = .02). Independent risk factors for death were cancer (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.2-20.8) and asymptomatic infection (OR, 6.7; 95% CI, 1.5-29.4) for C. fetus bacteremia, the absence of prescription of appropriate antibiotics (OR, 12.2; 95% CI, 0.9-157.5), and prescription of third-generation cephalosporins (OR, 10.2; 95% CI, 1.9-53.7) for bacteremia caused by other species. CONCLUSIONS: Campylobacter bacteremia occurs mainly in immunocompromised patients. Clinical features and risk factors of death differ by infection species.

Acquisition of multidrug-resistant Pseudomonas aeruginosa in patients in intensive care units: role of antibiotics with antipseudomonal activity.

A matched case-control study was performed to identify risk factors for acquiring multidrug-resistant Pseudomonas aeruginosa (MDRPA) in intensive care unit (ICU) patients during a 2-year period. MDRPA was defined as P. aeruginosa with combined decreased susceptibility to piperacillin, ceftazidime, imipenem, and ciprofloxacin. Thirty-seven patients who were colonized or infected with MDRPA were identified, 34 of whom were matched with 34 control patients who had cultures that showed no growth of P. aeruginosa. Matching criteria were severity of illness and length of ICU stay, with each control patient staying in the ICU for at least as long as the time period between the corresponding case patient's admission to the ICU and the acquisition of MDRPA. Baseline demographic and clinical characteristics and the use of invasive procedures were similar for case patients and control patients. Multivariate analysis identified duration of ciprofloxacin treatment as an independent risk factor for MDRPA acquisition, whereas the duration of treatment with imipenem was of borderline significance. These data support a major role for the use of antibiotics with high antipseudomonal activity, particularly ciprofloxacin, in the emergence of MDRPA.

Eradication of an outbreak of vancomycin-resistant Enterococcus (VRE): the cost of a failure in the systematic screening.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are still a concern in hospital units tending to seriously ill patients. However, the cost-effectiveness of active surveillance program to identify asymptomatically VRE colonized patient remains debatable. This work aims at evaluating the cost of a failure in the active surveillance of VRE that had resulted in an outbreak in a French University Hospital. FINDINGS: A VRE outbreak was triggered by a failure in the systematic VRE screening in a medico-surgical ward specialised in liver transplantation as a patient was not tested for VRE. This failure was likely caused by the reduction of healthcare resource. The outbreak involved 13 patients. Colonized patients were grouped in a dedicated part of the infectious diseases unit and tended by a dedicated staff. Transmission was halted within two months after discovery of the index case.The direct cost of the outbreak was assessed as the cost of staffing, disposable materials, hygiene procedures, and surveillance cultures.The loss of income from spare isolation beds was computed by difference with the same period in the preceding year. Payments were drawn from the hospital database. The direct cost of the outbreak (2008 Euros) was €60 524 and the loss of income reached €110 915. CONCLUSIONS: Despite this failure, the rapid eradication of the VRE outbreak was a consequence of the rapid isolation of colonized patient. Yet, eradicating even a limited outbreak requires substantial efforts and resources. This underlines that special attention has to be paid to strictly adhere to active surveillance program.