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Background: Intercontinental travel contributes to the spread of extended-spectrum beta-lactamase producing Enterobacterales (ESBL-PE). We assessed risk factors for intestinal ESBL-PE colonization in people travelling to low and middle income countries in the tropics and subtropics to better understand how travel affects ESBL-PE spread., Method: This prospective cohort study in travellers attending a travel clinic in Leipzig, Germany was conducted in 2016-2017. Information on risk factors related to travel, symptoms, antibiotic use, health care usage, accommodation, destination, diet and hygiene was collected by questionnaire after travel. Stools were phenotypically tested for ESBL-PE before and after travel. Risk factors for ESBL-PE colonization were identified using logistic regression., Results: Of the 230 travellers that were ESBL-PE negative before travelling, 23% (n = 53) travellers returned positive. Multivariable analyses showed that age, type of accommodation and travelling to Asia were associated with ESBL-PE colonization., Conclusions: Given that a considerable amount of travellers returned with ESBL-PE, we recommend raising awareness in returning high-risk travellers, e.g. those returning from high-risk areas. They should be aware that they may carry antimicrobial-resistant bacteria after travel, and how they can prevent its spread. The role of the type of accommodation as a factor favouring intestinal colonization with ESBL-PE requires further investigation., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction:  The prevalence of alveolar echinococcosis (AE) and cystic echinococcosis (CE) in Germany is increasing. The number of cases in northern and eastern regions is low, so there is little experience with regard to diagnosis and therapy., Objectives:  The objective of this paper was to evaluate the management of suspected and/or diagnosed echinococcosis at a university center in a low-prevalence region., Methods:  All the patients at the Leipzig University Hospital between 2004 and 2018 who had been serologically examined for echinococci were included in a retrospective cohort study. Clinical course, imaging, histology, therapeutic characteristics, relevant comorbidities and risk factors for AE and CE were evaluated. A time-staggered prevalence estimation, as well as sensitivity and specificity calculations for the serological tests, were performed., Results:  A total of 382 patients were enrolled, with 11 AE and 7 CE cases identified. The mean prevalence rate of AE in this cohort was 2.9 % and that of CE was 1.8 %. Among the patients, 56 % had known risk factors for AE and CE. The serological tests showed a sensitivity of 86 % and a specificity of 91 %. Two patients with false-negative serology were diagnosed by biopsy. All CE and 5 AE patients (45 %) were operated on. Six AE patients received long-term treatment with albendazole., Conclusions:  AE and CE are rare diseases in the greater Leipzig region; however, case numbers are on the rise. Due to favorable factors such as the escalation of migration, a further increase is expected. Diagnosis and therapy are challenging and should be supported by specialists (experienced infectiologists, imaging experts and skilled hepatobiliary surgeons) who should be integrated in a German network., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

The incidence of Clostridium difficile infections (CDI) remains on a high level globally. In Germany, the burden of disease and especially the number of severe or even lethal cases continue to increase. The main risk factor for the development of CDI is the exposure to broad-spectrum antibiotics, which disturb the intestinal microbiota and therefore enable the colonization with C. difficile. According to IDSA's and SHEA's updated US guidelines, vancomycin is the treatment of choice. Fidaxomicin is as effective as vancomycin, but its advantage is the lower rate of recurrence. For the treatment of multiple relapsing CDI, there are assured treatment successes of ≥ 90 % through a fecal microbiome transfer (FMT), whereby FMT in Germany currently only has the status of an individual therapeutic attempt. Thus, an evidence-based general recommendation for clinical practice is not possible. Currently, new antibiotics with narrow-spectrum activity and low intestinal resorption have been developed for the treatment of CDI, including surotomycin, cadazolid, and ridinilazol. Furthermore, recent clinical studies demonstrated that significantly fewer recurrences occurred in patients who additionally received the monoclonal antibody bezlotoxumab. Novel toxoid vaccines are expected to become an efficacious tool in the prevention of CDI. However, pivotal clinical trials have so far not been completed., Competing Interests: CL erhielt Vortragshonorare von den Firmen MSD und Astellas sowie Beratungshonorare von der Firma MSD. NL und AvB geben an, dass keine Interessenkonflikte vorliegen., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: From July 2010-April 2013, Leipzig University Hospital experienced the largest outbreak of a Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing Klebsiella pneumoniae (KPC-2-Kp) strain observed in Germany to date. After termination of the outbreak, we aimed to reconstruct transmission pathways by phylogenetics based on whole-genome sequencing (WGS)., Methods: One hundred seventeen KPC-2-Kp isolates from 89 outbreak patients, 5 environmental KPC-2-Kp isolates, and 24 K pneumoniae strains not linked to the outbreak underwent WGS. Phylogenetic analysis was performed blinded to clinical data and based on the genomic reads., Results: A patient from Greece was confirmed as the source of the outbreak. Transmission pathways for 11 out of 89 patients (12.4%) were plausibly explained by descriptive epidemiology, applying strict definitions. Five of these and an additional 15 (ie, 20 out of 89 patients [22.5%]) were confirmed by phylogenetics. The rate of phylogenetically confirmed transmissions increased significantly from 8 out of 66 (12.1% for the time period before) to 12 out of 23 patients (52.2% for the time period after; P <.001) after implementation of systematic screening for KPC-2-Kp (33,623 screening investigations within 11 months). Using descriptive epidemiology, systematic screening showed no significant effect (7 out of 66 [10.6%] vs 4 out of 23 [17.4%] patients; P = .465). The phylogenetic analysis supported the assumption that a contaminated positioning pillow served as a reservoir for the persistence of KPC-2-Kp., Conclusions: Effective phylogenetic identification of transmissions requires systematic microbiologic screening. Extensive screening and phylogenetic analysis based on WGS should be started as soon as possible in a bacterial outbreak situation., (Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background  Botulism is a rare, life-threatening, time-critical neuroparalytic disease that is frequently a subject of differential diagnostic considerations. But there is much uncertainty regarding diagnosis and therapy. Rapid diagnosis, early antitoxin dose, consistent food hygiene and the sensitization of the population can help to reduce incidence, morbidity and mortality. Methods  This overview is based on an epidemiological data inquiry (RKI, ECDC, CDC, WHO) and a selective literature research (pubmed till March 2017). Additionally, the German botulism guideline (2012) and own diagnostical experiences were taken into account. Results  The incidence of botulinum toxin intoxication induced by ubiquitous spore-forming Clostridium botulinum (main representative) is < 0.01/100 000 EU citizens. Foodborne botulism is a pure intoxication syndrome (most common form) due to improperly prepared or incorrectly stored food. Wound and infant botulism are kinds of "toxico-infections". A "bulbar" neuroparalysis is a main symptom progressing to a flaccid tetraparesis up to respiratory paralysis. Infant botulism is presented non-specific and is treated only symptomatically; but a special human-derived antitoxin is available at international pharmacies. In case of suspected foodborne or wound botulism antitoxin must be administered as soon as possible, which may also be effective 24 hours after symptoms onset. There is no evidence for adjuvant treatment except of intensive care unit (ICU) therapy. Conclusion  Despite typical symptomatology botulism is often diagnosed too late. Early antitoxin administration and ICU therapy are crucial for survival. A consultant laboratory should be contacted for advice., Competing Interests: Interessenkonflikt: Die Autoren geben an, in den letzten drei Jahren wirtschaftliche Verbindungen zu folgenden Unternehmen gehabt zu haben: MSD, Pfizer, Basilea, Quintiles, Thermo-Fischer, Resorba., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: High antibiotic and antifungal concentrations in wastewater from anti-infective drug production may exert selection pressure for multidrug-resistant (MDR) pathogens. We investigated the environmental presence of active pharmaceutical ingredients and their association with MDR Gram-negative bacteria in Hyderabad, South India, a major production area for the global bulk drug market., Methods: From Nov 19 to 28, 2016, water samples were collected from the direct environment of bulk drug manufacturing facilities, the vicinity of two sewage treatment plants, the Musi River, and habitats in Hyderabad and nearby villages. Samples were analyzed for 25 anti-infective pharmaceuticals with liquid chromatography-tandem mass spectrometry and for MDR Gram-negative bacteria using chromogenic culture media. In addition, specimens were screened with PCR for bla VIM , bla KPC , bla NDM , bla IMP-1 , and bla OXA-48 resistance genes., Results: All environmental specimens from 28 different sampling sites were contaminated with antimicrobials. High concentrations of moxifloxacin, voriconazole, and fluconazole (up to 694.1, 2500, and 236,950 µg/L, respectively) as well as increased concentrations of eight other antibiotics were found in sewers in the Patancheru-Bollaram industrial area. Corresponding microbiological analyses revealed an extensive presence of extended-spectrum beta-lactamase and carbapenemase-producing Enterobacteriaceae and non-fermenters (carrying mainly bla OXA-48 , bla NDM , and bla KPC ) in more than 95% of the samples., Conclusions: Insufficient wastewater management by bulk drug manufacturing facilities leads to unprecedented contamination of water resources with antimicrobial pharmaceuticals, which seems to be associated with the selection and dissemination of carbapenemase-producing pathogens. The development and global spread of antimicrobial resistance present a major challenge for pharmaceutical producers and regulatory agencies.

Background: Acute cholangitis (AC) requires the immediate initiation of antibiotic therapy in addition to treatment for biliary obstruction. Against a background of an increasing prevalence of multi-drug resistant (MDR) bacteria, the risk factors for the failure of empiric therapy must be defined., Methods: Using a pathogen-based approach, 1764 isolates from positive bile duct cultures were retrospectively analyzed to characterize the respective pathogen spectra in two German tertiary centers. Using a patient-based approach, the clinical and laboratory data for 83 patients with AC were assessed to identify risk factors for AC with pathogens resistant to the applied empiric therapy., Results: Bile cultures were predominantly polymicrobial, and empiric antibiotic therapies did not cover the full biliary pathogen spectrum in 78% of cases. MDR bacteria were isolated from the bile of 24/83 (29%) patients. The univariate risk factors for biliary MDR bacteria were male sex, nosocomial AC, prior antibiotic exposure and prior biliary stenting, of which biliary stenting was the only independent risk factor according to multivariate analysis (OR = 3.8; 95% CI 1.3-11.0, P = 0.013). Although there were no significant differences in survival or hospital stay in AC patients with and without detected biliary MDR pathogens, the former more often had a concomitant bloodstream infection (58% vs. 24%; P = 0.019), including those involving MDR pathogens or fungi (21% vs. 2%; P = 0.007)., Conclusion: Patients with biliary stents who develop AC should receive empiric therapy covering enterococci and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. These patients are at an increased risk for bloodstream infections by MDR pathogens or fungi., Competing Interests: The authors have declared that no competing interests exist.

This article reports on a previously healthy 17-month-old boy who developed pulmonary mucormycosis after a near-drowning incident in a goose pond. The patient survived without neurological sequelae and recovered, under treatment with amphotericin B, from the rare and often invasive fungal infection with Rhizopus spp., usually occurring in immunodeficient patients.

Background: Plastic stents used for the treatment of biliary obstruction will become occluded over time due to microbial colonization and formation of biofilms. Treatment of stent-associated cholangitis is often not effective because of inappropriate use of antimicrobial agents or antimicrobial resistance. We aimed to assess the current bacterial and fungal etiology of stent-associated biofilms, with particular emphasis on antimicrobial resistance., Methods: Patients with biliary strictures requiring endoscopic stent placement were prospectively enrolled. After the retrieval of stents, biofilms were disrupted by sonication, microorganisms were cultured, and isolates were identified by matrix-associated laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and/or biochemical typing. Finally, minimum inhibitory concentrations (MICs) were determined for various antimicrobial agents. Selected stents were further analyzed by fluorescence in situ hybridization (FISH)., Results: Among 120 patients (62.5% males, median age 64 years) with biliary strictures (35% malignant, 65% benign), 113 double pigtail polyurethane and 100 straight polyethylene stents were analyzed after a median indwelling time of 63 days (range, 1-1274 days). The stent occlusion rate was 11.5% and 13%, respectively, being associated with a significantly increased risk of cholangitis (38.5% vs. 9.1%, P<0.001). Ninety-five different bacterial and 13 fungal species were detected; polymicrobial colonization predominated (95.8% vs. 4.2%, P<0.001). Enterococci (79.3%), Enterobacteriaceae (73.7%), and Candida spp. (55.9%) were the leading pathogens. Candida species were more frequent in patients previously receiving prolonged antibiotic therapy (63% vs. 46.7%, P = 0.023). Vancomycin-resistant enterococci accounted for 13.7%, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae with co-resistance to ciprofloxacin accounted for 13.9%, and azole-resistant Candida spp. accounted for 32.9% of the respective isolates., Conclusions: Enterococci and Candida species play an important role in the microbial colonization of biliary stents. Therefore, empirical antimicrobial treatment of stent-associated cholangitis should be guided toward enterococci, Enterobacteriaceae, streptococci, anaerobes, and Candida. To determine causative pathogens, an accurate microbiological analysis of the extracted stent(s) may be helpful.

Introduction: Malaria is a widespread mosquito-borne infectious disease with over 300 million cases and roughly 900 thousand deaths in 2013. Cerebral involvement of malaria causes 50 % of all infection-associated deaths, especially in children below the age of 5 years. Hydrocephalus is a medical condition with abnormal accumulation of cerebrospinal fluid in physiological cavities and ventricles. Standard treatment is the implantation of a cerebrospinal fluid shunt device. A common problem associated with shunt treatment especially in pediatric patients is infection and consecutive shunt dysfunction caused by bacteriae or high protein levels clogging the valve. In these cases, Staphylococcus aureus and Staphylococcus epidermidis are predominantly found in CSF cultures., Case Presentation: We present a case of a 2-year old boy from Saudi Arabia with a ventriculoperitoneal (VP)-shunt-dependent congenital hydrocephalus who suffered from cerebral malaria and developed consecutive shunt failure., Conclusion: To the best of our knowledge, shunt failure caused by malaria CNS infection with Plasmodium falciparum has not yet been reported in the literature and should be considered as a rare cause of VP-shunt failure in patients with atypical VP-shunt infections living in or traveling from endemic areas.

Background: Toxigenic strains of Clostridium (C.) difficile are the most prevalent pathogens of antibiotic associated intestinal disease and nosocomial diarrhoea. During the last 10 years, incidences of C. difficile infection (CDI) have increased worldwide., Materials and Methods: With clinical and microbiological original data for 2002-2012 from the University Hospitals Leipzig and Halle (Saale), Germany, the authors illustrate the current situation regarding CDI in the states of Saxony and Saxony-Anhalt and exemplify the latest developments in terms of incidence, prevalence of resistance, diagnosis and treatment strategies regarding CDI with an emphasis on surgical options., Results: Following the general trend, at the University Hospitals of Leipzig and Halle (Saale) there was also an increase in incidence of CDI, especially of severe clinical courses. In primary and secondary care facilities, prevention of CDI is based on hygiene management and restricted usage of antibiotics, preferably as "Antibiotic Stewardship" programmes. In 2012, the new macrocyclic antibiotic Fidaxomicin was approved in the European Union for the treatment of CDI. The therapeutic armamentarium, previously based on metronidazole or vancomycin, has now been enriched by a substance that presumably will reduce the rate of recurrence of CDI. Moreover, early data from case series and controlled trials suggest that the re-establishment of eubiosis in the colon of patients with recurrent CDI by stool transplantation from healthy donors is an alternative to antibiotics. Standard surgical intervention for refractory CDI is subtotal colectomy with terminal ileostomy. In patients with adequate life expectancy and without organ dysfunction, a colon-saving surgical technique should be considered., Conclusion: Taking antibiotics for most remains the main risk factor for suffering from symptomatic CDI. With the introduction of Fidaxomicin there is hope for an improvement in the conservative treatment of CDI. Stool transplants from healthy donors are now considered to be better than giving antibiotics for severe CDI, but this treatment has not found broad acceptance yet. In cases with a lack of early treatment success, the surgeon must be consulted. Here, the evidence for preferably colon-saving surgical procedures is so far unfortunately low., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: The natural progress of intestinal colonization with Klebsiella pneumoniae carbapenemase-2-producing K pneumoniae (KPC-2-KP) is almost unknown., Methods: After a large, single-center outbreak of KPC-2-KP, we analyzed carrier prevalence through retrospective and prospective investigation of intestinal KPC-2-KP carriage 1 month, 3 months, 6 months, 1 year, and 2 years after acquisition, defined as the earliest date of KPC-2-KP detection. Rectal swabs or stool samples were collected at baseline and at each visit and submitted for both culture and KPC-specific polymerase chain reaction. Resolution of intestinal KPC-2-KP carriage was defined as a minimum of 3 consecutive negative polymerase chain reaction test results separated by at least 48 hours., Results: In patients available for long-term evaluation 26 out of 84 patients (31%) tested negative for KPC-2-KP after 1 month, 14 out of 34 (41%) after 3 months, 17 out of 26 (65%) after 6 months, 14 out of 19 (74%) after 1 year, and 5 out of 6 (83%) after 2 years. Decolonization of KPC-2-KP was hampered in patients with prolonged or repeated hospitalization (P = .044-.140, depending on the time interval). Two patients retested positive for KPC-2-KP after they had previously shown 3 consecutive negative tests. The longest positive KPC-2-KP carrier status so far was observed after nearly 40 months (1,191 days)., Conclusions: The majority of patients experienced spontaneous decolonization within 6 months after acquisition, mainly after discharge from the hospital. However, long-term carriage of >3 years is possible. Appropriate infection control measures must be taken when these patients are readmitted to health care facilities. A series of at least 4 consecutive negative rectal swabs or stool samples separated by sufficient time intervals appears necessary before the declaration of successful KPC-2-KP decolonization is made., (Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)