[CF Lung Disease - a German S3 Guideline: Pseudomonas aeruginosa]. / S3-Leitlinie: Lungenerkrankung bei Mukoviszidose ­ Pseudomonas aeruginosa.

Cystic Fibrosis (CF) is the most common autosomal recessive genetic multisystemic disease. In Germany, it affects at least 8000 people. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the airway epithelial lining fluid which leads to reduction of the mucociliary clearance.Even if highly effective, CFTR modulator therapy has been available for some years and people with CF are getting much older than before, recurrent and chronic infections of the airways as well as pulmonary exacerbations still occur. In adult CF life, Pseudomonas aeruginosa (PA) is the most relevant pathogen in colonisation and chronic infection of the lung, leading to further loss of lung function. There are many possibilities to treat PA-infection.This is a S3-clinical guideline which implements a definition for chronic PA-infection and demonstrates evidence-based diagnostic methods and medical treatment in order to give guidance for individual treatment options.

Terlipressin therapy is associated with increased risk of colonisation with multidrug-resistant bacteria in patients with decompensated cirrhosis.

BACKGROUND: Patients with cirrhosis are susceptible to develop bacterial infections that trigger acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Infections with multidrug-resistant organisms (MDRO) are associated with deleterious outcome. MDRO colonisation frequently proceeds MDRO infections and antibiotic therapy has been associated with MDRO colonisation. AIM: The aim of the study was to assess the influence of non-antibiotic medication contributing to MDRO colonisation. METHODS: Three hundred twenty-four patients with AD and ACLF admitted to the ICU of Frankfurt University Hospital with MDRO screening were included. Regression models were performed to identify drugs associated with MDRO colonisation. Another cohort (n = 129) from Barcelona was included to validate. A third multi-centre cohort (n = 203) with metagenomic sequencing data of stool was included to detect antibiotic resistance genes. RESULTS: A total of 97 patients (30%) were identified to have MDRO colonisation and 35 of them (11%) developed MDRO infection. Patients with MDRO colonisation had significantly higher risk of MDRO infection than those without (p = 0.0098). Apart from antibiotic therapy (odds ratio (OR) 2.91, 95%-confidence interval (CI) 1.82-4.93, p < 0.0001), terlipressin therapy in the previous 14 days was the only independent covariate associated with MDRO colonisation in both cohorts, the overall (OR 9.47, 95%-CI 2.96-30.23, p < 0.0001) and after propensity score matching (OR 5.30, 95%-CI 1.22-23.03, p = 0.011). In the second cohort, prior terlipressin therapy was a risk factor for MDRO colonisation (OR 2.49, 95% CI 0.911-6.823, p = 0.075) and associated with risk of MDRO infection during follow-up (p = 0.017). The validation cohort demonstrated that antibiotic inactivation genes were significantly associated with terlipressin administration (p = 0.001). CONCLUSIONS: Our study reports an increased risk of MDRO colonisation in patients with AD or ACLF, who recently received terlipressin therapy, while other commonly prescribed non-antibiotic co-medications had negligible influence. Future prospective trials are needed to confirm these results.

Coinfections and antimicrobial treatment in a cohort of falciparum malaria in a non-endemic country: a 10-year experience.

INTRODUCTION: Falciparum malaria remains one of the deadliest infectious diseases worldwide. In Germany, it is mainly an imported infection among travellers. Rates of coinfection are often unknown, and a clinical rationale for the beneficial use of calculated antibiotic therapy in patients with malaria and suspected coinfection is lacking. METHODS: We conducted an analysis of all in-patients treated with falciparum malaria at a German infectious diseases centre in vicinity to one of Europe's major airports for 2010-2019. Logistic regression and time-to-event analysis were used to evaluate predictors for bacterial coinfection, the use of antibacterial substances, as well as their influence on clinical course. RESULTS: In total, 264 patients were included. Of those, 64% received an additional antibacterial therapy (n = 169). Twenty-nine patients (11.0%) were found to have suffered from a relevant bacterial coinfection, while only a small fraction had relevant bacteremia (n = 3, 1.4%). However, patients with severe malaria did not suffer from coinfections more frequently (p = 0.283). CRP levels were not a reliable predictor for a bacterial coinfection (OR 0.99, 95% CI 0.94-1.06, p = 0.850), while another clinical focus of infection was positively associated (OR 3.86, 95% CI 1.45-11.55, p = 0.010). CONCLUSION: Although bacterial coinfections were rare in patients with malaria at our centre, the risk does not seem negligible. These data point rather towards individual risk assessment in respective patients than to general empiric antibiotic use.

Short Versus Long Antibiotic Therapy and Risk of Recurrence of Acute Cholangitis Due to Malignant Biliary Strictures.

Malignancies can cause severe stenosis of the biliary tract and therefore predispose a patient to bacterial cholangitis. Upon endoscopic drainage, antibiotic therapy (AT) is performed according to individual clinical judgement, as the optimal duration of AT is unclear to date, especially in the case of multidrug-resistant organisms (MDROs). In a case-based retrospective study, patients with malignant biliary strictures and acute cholangitis were included upon endoscopic retrograde cholangiography (ERC). The outcome of cases treated with short AT (≤6 days) was compared to that of long AT (≥7 days). Recurrent cholangitis (RC) before scheduled stent exchange was the primary end point. In total, 124 patients were included, with 183 cases of proven cholangitis in total. The overall median duration of AT was 7 days (range 1-20), with 74 cases (40%) receiving short AT and 109 (60%) receiving long AT. Short AT was not an independent risk factor for RC (HR = 0.66, p > 0.2), while colonization with MDROs was associated with a higher risk of RC (HR = 2.21, p = 0.005). Placement of a metal stent was associated with minor risk of RC (HR = 0.4, p = 0.038). In conclusion, short AT is possible in selected patients with non-severe cholangitis and malignant biliary strictures. Scheduled screening for MDROs is recommended and placement of a metal stent should be performed if possible.

Analysis of Mould Exposure of Immunosuppressed Patients at a German University Hospital.

Moulds are ubiquitous components of outdoor and indoor air and local conditions, temperature, humidity and season can influence their concentration in the air. The impact of these factors on mould exposure in hospitals and the resulting risk of infection for low to moderately immunocompromised patients is unclear. In the present retrospective analysis for the years 2018 to 2022, the monthly determined mould contamination of the outdoor and indoor air at the University Hospital Frankfurt am Main is compared with the average air temperature and the relative humidity. Mould infections (Aspergillus spp., Mucorales) of low to moderately immunosuppressed patients of a haematological-oncological normal ward were determined clinically according to the criteria of the European Organisation for Research and Treatment of Cancer (EORTC, Brussels, Belgium) and of the National Reference Centre for Surveillance of Nosocomial Infections (NRC-NI, Berlin, Germany). The data revealed that in the summer months (May-October), increased mould contamination was detectable in the outdoor and indoor air compared to the winter months (November-April). The mould levels in the patient rooms followed the detection rates of the outdoor air. Two nosocomial Aspergillus infections, one nosocomial Mucorales (Rhizopus spp.) infection (according to both NRC-NI and EORTC criteria) and five Aspergillus spp. infections (according to EORTC criteria) occurred in 4299 treated patients (resulting in 41,500 patient days). In our study, the incidence density rate of contracting a nosocomial mould infection (n = 3) was approximately 0.07 per 1000 patient days and appears to be negligible.

Time discrepancy for tuberculosis-negative microscopy and culture - the diagnostic gap remains: systematic analysis from a large tertiary care tuberculosis-clinic, Germany 2013-2017.

OBJECTIVES: Patients with open pulmonary tuberculosis (opTB) are subject to strict isolation rules. Sputum smear microscopy is used to determine infectivity, but sensitivity is lower than for culture. This study aimed to investigate the clinical relevance of this mismatch in contemporary settings. METHODS: Differential results between microscopy and culture were determined at the time of microscopic sputum conversion, from all patients with opTB between 01/2013 and 12/2017. In addition, data on HIV, multi/extensive drug-resistant TB status, time to smear- and cultural-negativity conversion were analyzed; and a Kaplan-Meier curve was developed. RESULTS: Of 118 patients with opTB, 58 had demographic data available for microbiological and clinical follow-up analysis; among these, 26 (44.8%) had still at least one positive culture result. Median time from opTB-treatment initiation to full microscopic sputum- or culture conversion, was 16.5 days (range 2-105), and 20 days (1-105), respectively (median difference: +3.5 days). Sixteen days after de-isolation, >90% had converted culturally. HIV- or multi/extensive drug-resistant TB status did not impact conversion time. CONCLUSION: When patients with opTB were de-isolated after 3 negative sputum smear microscopy tests, a substantial part still revealed cultural growth of Mycobacterium tuberculosis complex, but it remains unclear, whether smear-negative and culturally-positive individuals on therapy are really infective. Thus, the clinical relevance of this finding warrants further investigation.

CHROMAgar™ LIN-R as an efficient screening tool to assess the prevalence of linezolid-resistant enterococci in German hospital patients-a multicentre study approach, 2021-2022.

BACKGROUND: In recent years, an increasing number of linezolid-resistant enterococci (LRE) was recognized at the German National Reference Centre (NRC) for Enterococci. National guidelines on infection prevention recommend screening for LRE in epidemiologically linked hospital settings without referring to a reliable and rapid diagnostic method. Since 2020, CHROMAgar™ provide a chromogenic linezolid screening agar, LIN-R, suitable to simultaneously screen for linezolid-resistant staphylococci and enterococci. OBJECTIVES: To assess the applicability of CHROMAgar™ LIN-R in clinical settings for detecting LRE directly from patient material and to infer prevalence rates of LRE amongst German hospital patients. METHODS: During the 3-month trial period, clinical samples were plated on CHROMAgar™ LIN-R. Antimicrobial susceptibility testing was performed using VITEK2 or disc diffusion. At the NRC, linezolid resistance was determined by broth microdilution, multiplex-PCR for cfr/optrA/poxtA and by a restriction-based assay for 23S rDNA mutations. RESULTS: The 12 participating study sites used 13 963 CHROMAgar™ LIN-R plates during the study period. Of 442 presumptive LRE, 192 were confirmed by phenotypic methods. Of these, 161 were received by the NRC and 121 (75%) were verified as LRE. Most of LR-E. faecium 53/81 (65%) exhibited a 23S rRNA gene mutation as the sole resistance-mediating mechanism, whereas optrA constituted the dominant resistance trait in LR-E. faecalis [39/40 (98%)]. Prevalence of LRE across sites was estimated as 1% (ranging 0.18%-3.7% between sites). CONCLUSIONS: CHROMAgar™ LIN-R represents a simple and efficient LRE screening tool in hospital settings. A high proportion of false-positive results demands validation of linezolid resistance by a reference method.

Risk Factors and Role of Antibiotic Prophylaxis for Wound Infections after Percutaneous Endoscopic Gastrostomy.

BACKGROUND AND STUDY AIM: The incidence of wound infections after percutaneous endoscopic gastrostomy (PEG) varies widely in recent studies. The present study systematically investigates the underlying risk factors for the development of wound infections in a large cohort of patients over a long-term follow-up period. PATIENTS AND METHODS: A retrospective cohort study of patients undergoing PEG insertion using either the pull or push technique was conducted and patients followed up for 3 years. Tube-related wound infections were identified, and pathogens regularly cultured from wound swabs. Adjusted analysis was performed via univariate and multivariate logistic regression analysis. RESULTS: 616 patients were included in this study. A total of 25% percent of patients developed wound infections upon PEG tube insertion and 6.5% showed recurrent infections. Nicotine abuse (p = 0.01), previous ischemic stroke (p = 0.01) and head and neck cancer (p < 0.001) showed an increased risk for wound infection after PEG placement. Moreover, radio-chemotherapy was associated with the occurrence of wound infections (p < 0.001). Infection rates were similar between pull and push cohorts. The most common bacterial pathogen detected was Enterobacterales (19.2%). Staphylococcus aureus, Pseudomonas aeruginosa and enterococci were frequently detected in recurrent infection (14.2%, 11.4% and 9.6%, respectively). Antibiotic prophylaxis showed no effect on infection rates. CONCLUSIONS: Wound infections after PEG placement are common and occasionally occur as recurrent infections. There is potential for improvement in everyday clinical practice, particularly regarding antibiotic prophylaxis in accordance with guidelines.

Clinical characteristics and outcome of Mycobacterium chimaera infections after cardiac surgery: systematic review and meta-analysis of 180 heater-cooler unit-associated cases.

OBJECTIVES: Since 2013, heater-cooler unit (HCU) associated Mycobacterium chimaera infections linked to a global outbreak have been described. These infections were characterised by high morbidity and mortality due to delayed diagnosis, as well as challenges in antimycobacterial and surgical therapy. This study aimed to investigate the clinical characteristics and outcome of published cases of HCU-associated M. chimaera infections. METHODS: We searched PubMed and the Web of Science until 15 June 2022 for case reports, case series, and cohort studies, without language restriction, on patients with M. chimaera infection and a prior history of cardiac surgery. In this systematic review of case reports, no risk of bias assessment could be performed. Clinical, microbiological, and radiological features were recorded. Logistic regression and time-to-event analyses were performed to identify the potential factors associated with better survival. RESULTS: One hundred eighty patients from 54 publications were included. Most patients underwent surgical aortic valve (67.0%; 118/176 of patients with available data) or combined aortic valve and root replacement (15.3%; 27/176). The median period between the time point of surgery and the first symptoms was 17 months (interquartile range 13-26 months). The overall case fatality rate was 45.5% (80/176), with a median survival of 24 months after the initiation of antimycobacterial therapy or diagnosis. A reoperation (including the removal or exchange of foreign material) was associated with better survival in multivariate logistic regression (OR 0.32 for lethal events; 95% CI 0.12-0.79; p 0.015) and in time-to-event analysis (p 0.0094). DISCUSSION: This systematic review and meta-analysis confirm the high overall mortality of HCU -associated disseminated M. chimaera infections after cardiac surgery. A reoperation seems to be associated with better survival. Physicians have to stay aware of this infection, as patients might still be present today due to the long latency period.

Immune signatures, testing, and management of febrile neutropenia in pediatric cancer patients.

INTRODUCTION: Infectious complications, particularly invasive bacterial and fungal infections, are still a major cause of morbidity in pediatric cancer patients and are associated with significant mortality. Over the last few years, there has been much effort in defining risk groups to tailor antimicrobial therapy, and in establishing pediatric-specific guidelines for antimicrobial strategies. AREAS COVERED: This review provides a critical overview of defining risk groups for infection, diagnostic work-up, antimicrobial prophylaxis, empirical therapy, and treatment of established infections. EXPERT OPINION: To date, no generalizable risk prediction model has been established for pediatric cancer patients. There is growing interest in defining the impact of the individual genetic background on infectious complications. New diagnostic tools have been developed over the last few years, but they need to be validated in pediatric cancer patients. International, pediatric-specific guidelines for antimicrobial prophylaxis, empirical therapy, and treatment of established infections have recently been published and will harmonize antimicrobial strategies in the future.

Molecular surveillance of multidrug-resistant Gram-negative bacteria in Ukrainian patients, Germany, March to June 2022.

BackgroundSince the beginning of the war in Ukraine in February 2022, Ukrainians have been seeking shelter in other European countries.AimWe aimed to investigate the prevalence and the molecular epidemiology of multidrug-resistant Gram-negative (MDRGN) bacteria and meticillin-resistant Staphylococcus aureus (MRSA) in Ukrainian patients at admittance to the University Hospital Frankfurt, Germany.MethodsWe performed screening and observational analysis of all patients from March until June 2022. Genomes of MDRGN isolates were analysed for antimicrobial resistance, virulence genes and phylogenetic relatedness.ResultsWe included 103 patients (median age: 39 ±â€¯23.7 years), 57 of whom were female (55.3%; 95% confidence interval (CI): 45.2-5.1). Patients were most frequently admitted to the Department of Paediatrics (29/103; 28.2%; 95% CI: 19.7-37.9). We found 34 MDRGN isolates in 17 of 103 patients (16.5%; 95% CI: 9.9-25.1). Ten patients carried 21 carbapenem-resistant (CR) bacteria, five of them more than one CR isolate. Four of six patients with war-related injuries carried eight CR isolates. In six of 10 patients, CR isolates caused infections. Genomic characterisation revealed that the CR isolates harboured at least one carbapenemase gene, bla NDM-1 being the most frequent (n = 10). Core genome and plasmid analysis revealed no epidemiological connection between most of these isolates. Hypervirulence marker genes were found in five of six Klebsiella pneumoniae CR isolates. No MRSA was found.ConclusionHospitals should consider infection control strategies to cover the elevated prevalence of MDRGN bacteria in Ukrainian patients with war-related injuries and/or hospital pre-treatment and to prevent the spread of hypervirulent CR isolates.

Colonization with multidrug-resistant organisms is associated with impaired survival of patients with surgically resected cholangiocarcinoma.

BACKGROUND & AIMS: Colonization with multidrug-resistant organisms (MDRO) has been shown to impair survival in patients with various malignancies. Despite the increasing spread of MDRO, its impact on patients with cholangiocarcinoma (CCA) is unclear. Aim of this study was to analyse the impact of MDRO-colonization on overall prognosis in CCA patients. METHODS: All patients with surgically resected CCA diagnosed between August 2005 and November 2021 at the University Hospital Frankfurt were screened for MDRO. CCA patients with a positive MDRO screening before or within the first 90 days after diagnosis of CCA were defined as colonized. Patients with a negative MDRO screening were defined as non-colonized. RESULTS: Hundred and sixty nine patients were included. 32% (n = 54) were screened MDRO positive, while 68% (115) were non-colonized. Median overall survival (OS) for colonized patients was 17.1 months (95% CI = 9-25.2 months) compared to 50 months (95% CI = 37.1-62.8) for MDRO-negative patients (p ≤ .001). Non-cancer-related mortality (p ≤ .001) and infectious-related death (p ≤ .001) was significantly higher in the MDRO-colonized group. In multivariate analysis, MDRO colonization (HR = 2.1, 95% CI = 1.4-3.3, p = .001), ECOG 1 (HR = 2.5, 95% CI = 1.6-4, p ≤ .001) and N1 status (HR = 1.7, 95% CI = 1.1-2.6, p = .017) were independent risk factors for OS. CONCLUSION: MDRO-colonization contributes to poor survival in patients with surgically resected CCA. MDRO surveillance is necessary to optimize clinical management of infections and to potentially reduce mortality in this critical population.

Molecular Epidemiology of Mycobacterium abscessus Isolates Recovered from German Cystic Fibrosis Patients.

Infections due to Mycobacterium abscessus are a major cause of mortality and morbidity in cystic fibrosis (CF) patients. Furthermore, M. abscessus has been suspected to be involved in person-to-person transmissions. In 2016, dominant global clonal complexes (DCCs) that occur worldwide among CF patients have been described. To elucidate the epidemiological situation of M. abscessus among CF patients in Germany and to put these data into a global context, we performed whole-genome sequencing of a set of 154 M. abscessus isolates from 123 German patients treated in 14 CF centers. We used MTBseq pipeline to identify clusters of closely related isolates and correlate those with global findings. Genotypic drug susceptibility for macrolides and aminoglycosides was assessed by characterization of the erm(41), rrl, and rrs genes. By this approach, we could identify representatives of all major DCCs (Absc 1, Absc 2, and Mass 1) in our cohort. Intrapersonal isolates showed higher genetic relatedness than interpersonal isolates (median 3 SNPs versus 16 SNPs; P < 0.001). We further identified four clusters with German patients from same centers clustering with less than 25 SNPs distance (range 3 to 18 SNPs) but did not find any hint for in-hospital person-to-person transmission. This is the largest study investigating phylogenetic relations of M. abscessus isolates in Germany. We identified representatives of all reported DCCs but evidence for nosocomial transmission remained inconclusive. Thus, the occurrence of genetically closely related isolates of M. abscessus has to be interpreted with care, as a direct interhuman transmission cannot be directly deduced. IMPORTANCE Mycobacterium abscessus is a major respiratory pathogen in cystic fibrosis (CF) patients. Recently it has been shown that dominant global clonal complexes (DCCs) have spread worldwide among CF patients. This study investigated the epidemiological situation of M. abscessus among CF patients in Germany by performing whole-genome sequencing (WGS) of a set of 154 M. abscessus from 123 German patients treated in 14 CF centers. This is the largest study investigating the phylogenetic relationship of M. abscessus CF isolates in Germany.

German Multicenter Study Analyzing Antimicrobial Activity of Ceftazidime-Avibactam of Clinical Meropenem-Resistant Pseudomonas aeruginosa Isolates Using a Commercially Available Broth Microdilution Assay.

Multidrug resistance is an emerging healthcare issue, especially concerning Pseudomonas aeruginosa. In this multicenter study, P. aeruginosa isolates with resistance against meropenem detected by routine methods were collected and tested for carbapenemase production and susceptibility against ceftazidime-avibactam. Meropenem-resistant isolates of P. aeruginosa from various clinical materials were collected at 11 tertiary care hospitals in Germany from 2017−2019. Minimum inhibitory concentrations (MICs) were determined via microdilution plates (MICRONAUT-S) of ceftazidime-avibactam and meropenem at each center. Detection of the presence of carbapenemases was performed by PCR or immunochromatography. For meropenem-resistant isolates (n = 448), the MIC range of ceftazidime-avibactam was 0.25−128 mg/L, MIC90 was 128 mg/L and MIC50 was 16 mg/L. According to EUCAST clinical breakpoints, 213 of all meropenem-resistant P. aeruginosa isolates were categorized as susceptible (47.5%) to ceftazidime-avibactam. Metallo-ß-lactamases (MBL) could be detected in 122 isolates (27.3%). The MIC range of ceftazidime-avibactam in MBL-positive isolates was 4−128 mg/L, MIC90 was >128 mg/L and MIC50 was 32 mg/L. There was strong variation in the prevalence of MBL-positive isolates among centers. Our in vitro results support ceftazidime-avibactam as a treatment option against infections caused by meropenem-resistant, MBL-negative P. aeruginosa.

Comparison of short-course antibiotic therapy of 6 or less days with a longer treatment in patients with cholangitis after liver transplantation.

OBJECTIVES: Stenosis of the biliary anastomosis predisposes liver graft recipients to bacterial cholangitis. Antibiotic therapy (AT) is performed according to individual clinical judgment, but duration of AT remains unclear. METHODS: All liver graft recipients with acute cholangitis according to the Tokyo criteria grade 1 and 2 after endoscopic retrograde cholangiography (ERC) were included. Outcome of patients treated with short AT (<7 days) was compared to long AT (>6 days). Recurrent cholangitis (RC) within 28 days was the primary end point. RESULTS: In total, 30 patients were included with a median of 313 (range 34-9849) days after liver transplantation until first proven cholangitis. Among 62 cases in total, 51/62 (82%) were graded as Tokyo-1 and 11/62 (18%) as Tokyo-2. Overall median duration of AT was 6 days (1-14) with 36 cases (58%) receiving short AT and 26 (42%) receiving long AT. RC was observed in 10 (16%) cases, without significant difference in occurrence of RC in short versus long AT cases. CRP and bilirubin were significantly higher in patients with long AT, while low serum albumin and low platelets were associated with risk of RC. CONCLUSION: A shorter antibiotic course than 7 days shows good results in selected, ERC-treated patients for post-transplantation biliary strictures.

Combined Clinical, Epidemiological, and Genome-Based Analysis Identified a Nationwide Outbreak of Burkholderia cepacia Complex Infections Caused by Contaminated Mouthwash Solutions.

Background: In September 2018, Burkholderia cepacia complex (BCC) infections in 3 patients associated with exposure to a mouthwash solution (MWS) were reported to the Robert Koch Institute (RKI). As the product was still on the market and the scale of the outbreak was unclear, a nation-wide investigation was initiated. Methods: We aimed to investigate BCC infections/colonizations associated with MWS. Hospitals, laboratories, and public health services were informed that BCC isolates should be sent to the RKI. These isolates were typed by pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) including development of an ad hoc core genome MLST (cgMLST) scheme. Results: In total, 36 patients from 6 hospitals met the case definition, the last patient in November 2018. Twenty-nine isolates from 26 of these patients were available for typing. WGS analysis revealed 2 distinct cgMLST clusters. Cluster 1 (Burkholderia arboris) contained isolates from patients and MWS obtained from 4 hospitals and isolates provided by the manufacturer. Patient and MWS isolates from another hospital were assigned to cluster 2 (B. cepacia). Conclusions: The combined clinical, epidemiological, and microbiological investigation, including whole-genome analysis, allowed for uncovering a supraregional BCC outbreak in health care settings. Strains of B. arboris and B. cepacia were identified as contaminating species of MWS bottles and subsequent colonization and putative infection of patients in several hospitals. Despite a recall of the product by the manufacturer in August 2018, the outbreak lasted until December 2018. Reporting of contaminated medical products and recalls should be optimized to protect patients.

Pseudomonas aeruginosa Affects Airway Epithelial Response and Barrier Function During Rhinovirus Infection.

Cystic fibrosis (CF) lung disease is aggravated by recurrent and ultimately chronic bacterial infections. One of the key pathogens in adult CF lung disease is P. aeruginosa (PA). In addition to bacteria, respiratory viral infections are suggested to trigger pulmonary exacerbations in CF. To date, little is known on how chronic infections with PA influence susceptibility and response to viral infection. We investigated the interactions between PA, human rhinovirus (HRV) and the airway epithelium in a model of chronic PA infection using differentiated primary bronchial epithelial cells (pBECs) and clinical PA isolates obtained from the respiratory sample of a CF patient. Cells were repeatedly infected with either a mucoid or a non-mucoid PA isolate for 16 days to simulate chronic infection, and subsequently co-infected with HRV. Key cytokines and viral RNA were quantified by cytometric bead array, ELISA and qPCR. Proteolytic degradation of IL-6 was analyzed by Western Blots. Barrier function was assessed by permeability tests and transepithelial electric resistance measurements. Virus infection stimulated the production of inflammatory and antiviral mediators, including interleukin (IL)-6, CXCL-8, tumor necrosis factor (TNF)-α, and type I/III interferons. Co-infection with a non-mucoid PA isolate increased IL-1ß protein concentrations (28.88 pg/ml vs. 6.10 pg/ml), but in contrast drastically diminished levels of IL-6 protein (53.17 pg/ml vs. 2301.33 pg/ml) compared to virus infection alone. Conditioned medium obtained from co-infections with a non-mucoid PA isolate and HRV was able to rapidly degrade recombinant IL-6 in a serine protease-dependent manner, whereas medium from individual infections or co-infections with a mucoid isolate had no such effect. After co-infection with HRV and the non-mucoid PA isolate, we detected lower mRNA levels of Forkhead box J1 (FOXJ1) and Cilia Apical Structure Protein (SNTN), markers of epithelial cell differentiation to ciliated cells. Moreover, epithelial permeability was increased and barrier function compromised compared to single infections. These data show that PA infection can influence the response of bronchial epithelial cells to viral infection. Altered innate immune responses and compromised epithelial barrier function may contribute to an aggravated course of viral infection in PA-infected airways.

Exclusion of Mucorales Co-Infection in a Patient with Aspergillus flavus Sinusitis by Fluorescence In Situ Hybridization (FISH).

Invasive fungal infections are associated with increased mortality in hematological patients. Despite considerable advances in antifungal therapy, the evaluation of suspected treatment failure is a common clinical challenge requiring extensive diagnostic testing to rule out potential causes, such as mixed infections. We present a 64-year-old patient with secondary AML, diabetes mellitus, febrile neutropenia, and sinusitis. While cultures from nasal tissue grew Aspergillus flavus, a microscopic examination of the tissue was suggestive of concomitant mucormycosis. However, fluorescence in situ hybridization (FISH) using specific probes targeting Aspergillus and Mucorales species ruled out mixed infection. This was confirmed by specific qPCR assays amplifying the DNA of Aspergillus, but not of Mucorales. These results provided a rational basis for step-down targeted therapy, i.e., the patient received posaconazole after seven days of calculated dual therapy with liposomal amphotericin B and posaconazole. Despite clinical response to the antifungal therapy, he died due to the progression of the underlying disease within two weeks after diagnosis of fungal infection. Molecular diagnostics applied to tissue blocks may reveal useful information on the etiology of invasive fungal infections, including challenging situations, such as with mixed infections. A thorough understanding of fungal etiology facilitates targeted therapy that may improve therapeutic success while limiting side effects.

Rectal colonization by resistant bacteria increases the risk of infection by the colonizing strain in critically ill patients with cirrhosis.

BACKGROUND & AIMS: It remains unclear whether rectal colonization with multidrug-resistant organisms (MDROs) is prevalent and predisposes to infections by the same pathogens in patients with cirrhosis. METHODS: Two series of critically ill patients were evaluated. In the Barcelona cohort, 486 consecutive patients were prospectively evaluated, 129 with and 357 without cirrhosis (2015-2016). Rectal swabs were performed at admission and weekly thereafter (until intensive care unit [ICU] discharge) to detect MDRO colonization. Risk factors for colonization and infection by MDROs were evaluated. A retrospective cohort from Frankfurt (421 patients with cirrhosis; 2010-2018) was investigated to evaluate MDRO rectal colonization in another epidemiological scenario. RESULTS: In the Barcelona cohort, 159 patients were colonized by MDROs (32.7%), 102 (64.2%) at admission and 57 (35.8%) during follow-up. Patients with cirrhosis showed higher rates of rectal colonization at admission than those without cirrhosis (28.7% vs. 18.2%, p = 0.01) but similar colonization rates during ICU stay. Extended-spectrum beta-lactamase-Enterobacterales were the most frequent MDROs isolated in both groups. Colonization by MDROs independently increased the risk of infection by MDROs at admission and during follow-up. Risk of new infection by the colonizing strain was also significantly increased in patients with (hazard ratio [HR] 7.41) and without (HR 5.65) cirrhosis. Rectal colonization by MDROs was also highly prevalent in Frankfurt (n = 198; 47%; 131 at admission [66.2%] and 67 [33.8%] during follow-up), with vancomycin-resistant enterococci being the most frequent colonizing organism. Rectal colonization by MDROs was also associated with an increased risk of infection by MDROs in this cohort. Infections occurring in MDR carriers were mainly caused by the colonizing strain. CONCLUSION: Rectal colonization by MDROs is extremely frequent in critically ill patients with cirrhosis. Colonization increases the risk of infection by the colonizing resistant strain. LAY SUMMARY: Rectal colonization by multidrug-resistant organisms (MDROs) is a prevalent problem in patients with cirrhosis requiring critical care. The pattern of colonizing bacteria is heterogeneous with relevant differences between centers. Colonization by MDROs is associated with increased risk of infection by the colonizing bacteria in the short term. This finding suggests that colonization data could be used to guide empirical antibiotic therapy and de-escalation policies in patients with cirrhosis.