Left ventricular assist device-associated driveline infections as a specific form of complicated skin and soft tissue infection/acute bacterial skin and skin structure infection - issues and therapeutic options.

PURPOSE OF REVIEW: This review comments on the current guidelines for the treatment of wound infections under definition of acute bacterial skin and skin structure infections (ABSSSI). However, wound infections around a catheter, such as driveline infections of a left ventricular assist device (LVAD) are not specifically listed under this definition in any of the existing guidelines. RECENT FINDINGS: Definitions and classification of LVAD infections may vary across countries, and the existing guidelines and recommendations may not be equally interpreted among physicians, making it unclear if these infections can be considered as ABSSSI. Consequently, the use of certain antibiotics that are approved for ABSSSI may be considered as 'off-label' for LVAD infections, leading to rejection of reimbursement applications in some countries, affecting treatment strategies, and hence, patients' outcomes. However, we believe driveline exit site infections related to LVAD can be included within the ABSSSI definition. SUMMARY: We argue that driveline infections meet the criteria for ABSSSI which would enlarge the 'on-label' antibiotic armamentarium for treating these severe infections, thereby improving the patients' quality of life.

The added value of (1,3)-ß-D-glucan for the diagnosis of Invasive Candidiasis in ICU patients: a prospective cohort study.

PURPOSE: Beta-D-Glucan (BDG) testing has been suggested to support the diagnosis of candidemia and invasive candidiasis. The actual benefit in critically ill high-risk patients in intensive care units (ICU) has not been verified so far. METHODS: In ICU patients receiving empirical echinocandin treatment for suspected invasive candidiasis (IC), serial BDG testing using the Fujifilm Wako Beta-Glucan Test was performed, starting on the first day of echinocandin administration and every 24-48 h afterwards. Diagnostic accuracy was determined for single testing and serial testing strategies using a range of cut-off values. In addition, we compared the added value of these testing strategies when their results were introduced as additional predictors into a multivariable logistic regression model controlling for established risk factors of IC. RESULTS: A total of 174 ICU patients, forty-six of which (25.7%) classified as cases of IC, were included in our study. Initial BDG testing showed moderate sensitivity (74%, 95%CI 59-86%) and poor specificity (45%, 95% CI 36-54%) for IC which could hardly be improved by follow-up testing. While raw BDG values or test results obtained with very high thresholds improved the predictive performance of our multivariable logistic regression model for IC, neither single nor serial testing with the manufacturer-proposed low-level cut-off showed substantial benefit. CONCLUSIONS: In our study of critically ill intensive care patients at high risk for candidemia or invasive candidiasis, diagnostic accuracy of BDG testing was insufficient to inform treatment decisions. Improved classification was only achieved for cases with very high BDG values.

Gentamicin combination treatment is associated with lower mortality in patients with invasive listeriosis: a retrospective analysis.

PURPOSE: Listeria monocytogenes causes severe bacterial infections with the highest mortality rate among foodborne pathogens in Europe. Combination treatment with ampicillin and gentamicin is recommended for invasive manifestations. However, evidence to support this treatment approach remains limited due to a lack of randomised controlled trials. To explore this critical issue further, we conducted this retrospective, single-center study. METHODS: We identified all patients hospitalized with invasive listeriosis at the University Medical Center Hamburg-Eppendorf between 2009 and 2020 and analyzed the effect of gentamicin combination treatment versus monotherapy on 90-day mortality. RESULTS: In total, 36 patients with invasive listeriosis were included, of which 21 patients received gentamicin combination treatment and 15 received monotherapy. The mean age-adjusted Charlson Comorbidity Index (aaCCI) value was lower in the gentamicin combination treatment group (5.4 vs. 7.4). Neurolisteriosis was more common in the gentamicin group (81% vs. 20%). The 90-day mortality was with significantly lower in the gentamicin combination treatment group (10%) compared to the monotherapy group (60%). Multivariable cox regression analysis, adjusted for a propensity score computed based on neurolisteriosis, aaCCI and sex, revealed a significantly reduced hazard ratio of 0.07 (95% CI: 0.01-0.53, p = 0.01) for 90-day mortality for the gentamicin combination treatment. CONCLUSION: This retrospective study highlights the benefit of gentamicin combination treatment in reducing the 90-day mortality rate among patients with invasive listeriosis. The high prevalence of monotherapy in this study cohort raises concerns about the adequacy of antibiotic therapy in clinical practice.

Exploring European Consensus About the Remaining Treatment Challenges and Subsequent Opportunities to Improve the Management of Invasive Fungal Infection (IFI) in the Intensive Care Unit.

BACKGROUND: The global prevalence of invasive fungal infections (IFI) is increasing, particularly within Intensive Care Units (ICU), where Candida spp. and Aspergillus spp. represent the most important pathogens. Diagnosis and management of IFIs becomes progressively challenging, with increasing antifungal resistance and the emergence of rare fungal species. Through a consensus survey focused on assessing current views on how IFI should be managed, the aim of this project was to identify challenges around diagnosing and managing IFIs in the ICU. The current status in different countries and perceived challenges to date amongst a multidisciplinary cohort of healthcare professionals involved in the care of IFI in the ICU was assessed. METHODS: Using a modified Delphi approach, an expert panel developed 44 Likert-scale statements across 6 key domains concerning patient screening and minimal standards for diagnosis of IFIs in ICU; initiation and termination of antifungal treatments and how to minimise their side effects and insights for future research on this topic. These were used to develop an online survey which was distributed on a convenience sampling basis utilising the subscriber list held by an independent provider (M3 Global). This survey was distributed to intensivists, infectious disease specialists, microbiologists and antimicrobial/ICU pharmacists within the UK, Germany, Spain, France and Italy. The threshold for consensus was set at 75%. RESULTS: A total of 335 responses were received during the five-month collection period. From these, 29/44 (66%) statements attained very high agreement (≥ 90%), 11/44 (25%) high agreement (< 90% and ≥ 75%), and 4/44 (9%) did not meet threshold for consensus (< 75%). CONCLUSION: The results outline the need for physicians to be aware of the local incidence of IFI and the associated rate of azole resistance in their ICUs. Where high clinical suspicion exists, treatment should start immediately and prior to receiving the results from any diagnostic test. Beta-D-glucan testing should be available to all ICU centres, with results available within 48 h to inform the cessation of empirical antifungal therapy. These consensus statements and proposed measures may guide future areas for further research to optimise the management of IFIs in the ICU.

Molecular monitoring of T-cell kinetics and migration in severe neurotoxicity after real-world CD19-specific chimeric antigen receptor T cell therapy.

CD19-specific chimeric antigen receptor (CD19-CAR) T-cell therapies mediate durable responses in late-stage B-cell malignancies, but can be complicated by a potentially severe immune effector cell-associated neurotoxicity syndrome (ICANS). Despite broad efforts, the precise mechanisms of ICANS are not entirely known, and resistance to current ICANSdirected therapies (especially corticosteroids) has been observed. Recent data suggest that inflammatory cytokines and/or targeting of cerebral CD19-expressing pericytes can disrupt the blood-brain barrier and facilitate influx of immune cells, including CAR T cells. However, specific tools for CD19-CAR T-cell analysis within often minute samples of cerebrospinal fluid (CSF) are not broadly available. Here, we applied our recently developed digital polymerase chain reaction assays to monitor CD19-CAR T-cell kinetics in CSF and blood in real-world patients with neurotoxicity. Consistently, we observed a CAR T-cell enrichment within CSF in ICANS patients with further progressive accumulation despite intense corticosteroid- containing immuno-chemotherapies in a subset of patients with prolonged and therapy-resistant grade 3-4 neurotoxicity. We used next-generation T-cell receptor-b sequencing to assess the repertoire of treatment-refractory cells. Longitudinal analysis revealed a profound skewing of the T-cell receptor repertoire, which at least partly reflected selective expansion of infused T-cell clones. Interestingly, a major fraction of eventually dominating hyperexpanded T-cell clones were of non-CAR T-cell derivation. These findings hint to a role of therapy-refractory T-cell clones in severe ICANS development and prompt future systematic research to determine if CAR T cells may serve as 'door openers' and to further characterize both CAR-positive and non-CAR T cells to interrogate the transcriptional signature of these possibly pathologic T cells.

Posaconazole exposure in critically ill ICU patients: a need for action.

PURPOSE: Posaconazole is an antifungal drug currently being used for prophylaxis and treatment of invasive fungal infections such as aspergillosis. To date, therapeutic drug monitoring (TDM) of posaconazole is recommended with the use of oral suspension, but the potential need of TDM with the use of IV formulations is rising. Therefore, we aimed to investigate the pharmacokinetics of IV posaconazole in critically ill patients. METHODS: In a prospective study, we analysed 168 consecutivelly collected posaconazole levels from 10 critically ill patients drawn during a 7 day curse. Posaconazole concentrations were measured using a chromatographic method. Demographic and laboratory data were collected, and the data was analysed using descriptive statistics. RESULTS: We included 168 posaconazole levels, resulting in a median trough of 0.62 [0.29-1.05] mg/L with 58% not reaching the suggested target of 0.5 mg/L for fungal prophylaxis. Moreover, 74% of the trough levels were under the target of 1 mg/L which is proposed for the treatment of aspergillosis. CONCLUSION: Posaconazole exposure is highly variable in critically ill patients resulting in potentially insufficient drug concentrations in many cases. TDM is highly recommended to identify and avoid underexposure. TRIAL REGISTRATION NUMBER: NCT05275179, March 11, 2022.

[Drug therapy interventions for acute SARS-CoV-2 infection: who, when, and what?] / Medikamentöse Therapiemaßnahmen bei akuter SARS-CoV-2-Infektion: wer, wann und was?

There is a variety of drug therapy options for treatment of acute SARS-CoV-2 infections. The updated S3 guideline "Recommendations for inpatient therapy of patients with COVID-19" provides clear recommendations in this regard. Which therapy is best suited for which patient and in which phase of the disease must be decided individually based on risk factors, comorbidities and contraindications. This article provides an overview.

The prevalence of early- and late-onset bacterial, viral, and fungal respiratory superinfections in invasively ventilated COVID-19 patients.

The role of respiratory superinfections in patients with coronavirus disease 2019 (COVID-19) pneumonia remains unclear. We investigated the prevalence of early- and late-onset superinfections in invasively ventilated patients with COVID-19 pneumonia admitted to our department of intensive care medicine between March 2020 and November 2020. Of the 102 cases, 74 (72.5%) received invasive ventilation and were tested for viral, bacterial, and fungal pathogens on Days 0-7, 8-14, and 15-21 after the initiation of mechanical ventilation. Approximately 45% developed one or more respiratory superinfections. There was a clear correlation between the duration of invasive ventilation and the prevalence of coinfecting pathogens. Male patients with obesity and those suffering from chronic obstructive pulmonary disease and/or diabetes mellitus had a significantly higher probability to develop a respiratory superinfection. The prevalence of viral coinfections was high, with a predominance of the herpes simplex virus (HSV), followed by cytomegalovirus. No respiratory viruses or intracellular bacteria were detected in our cohort. We observed a high coincidence between Aspergillus fumigatus and HSV infection. Gram-negative bacteria were the most frequent pathogen group. Klebsiella aerogenes was detected early after intubation, while Klebsiella pneumoniae and Pseudomonas aeruginosa were related to a prolonged respiratory weaning.

Clinical efficacy and in vitro neutralization capacity of monoclonal antibodies for severe acute respiratory syndrome coronavirus 2 delta and omicron variants.

We aimed to provide in vitro data on the neutralization capacity of different monoclonal antibody (mAb) preparations against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta and omicron variant, respectively, and describe the in vivo RNA kinetics of coronavirus disease 2019 (COVID-19) patients treated with the respective mAbs. Virus neutralization assays were performed to assess the neutralizing effect of the mAb formulations casirivimab/imdevimab and sotrovimab on the SARS-CoV-2 delta and omicron variant. Additionally, respiratory tract SARS-CoV-2 RNA kinetics are provided for 25 COVID-19 patients infected with either delta variant (n = 18) or omicron variant (n = 7) treated with the respective mAb formulations during their hospital stay. In the virus neutralization assay, sotrovimab exhibits neutralizing capacity at therapeutically achievable concentrations against the SARS-CoV-2 delta and omicron variant. In contrast, casivirimab/imdevimab had neutralizing capacity against the delta variant but failed neutralization against the omicron variant except for a very high concentration above the currently recommended therapeutic dosage. In patients with delta variant infections treated with casivirimab/imdevimab, we observed a rapid decrease of respiratory viral RNA at day 3 after mAb therapy. In contrast, no such prompt decline was observed in patients with delta variant or omicron variant infections receiving sotrovimab.

Comparison of four diagnostic criteria for invasive pulmonary aspergillosis-A diagnostic accuracy study in critically ill patients.

BACKGROUND: In the absence of lung biopsy, there are various algorithms for the diagnosis of invasive pulmonary aspergillosis (IPA) in critically ill patients that rely on clinical signs, underlying conditions, radiological features and mycology. The aim of the present study was to compare four diagnostic algorithms in their ability to differentiate between probable IPA (i.e., requiring treatment) and colonisation. METHODS: For this diagnostic accuracy study, we included a mixed ICU population with a positive Aspergillus culture from respiratory secretions and applied four different diagnostic algorithms to them. We compared agreement among the four algorithms. In a subgroup of patients with lung tissue histopathology available, we determined the sensitivity and specificity of the single algorithms. RESULTS: A total number of 684 critically ill patients (69% medical/31% surgical) were included between 2005 and 2020. Overall, 79% (n = 543) of patients fulfilled the criteria for probable IPA according to at least one diagnostic algorithm. Only 4% of patients (n = 29) fulfilled the criteria for probable IPA according to all four algorithms. Agreement among the four diagnostic criteria was low (Cohen's kappa 0.07-0.29). From 85 patients with histopathological examination of lung tissue, 40% (n = 34) had confirmed IPA. The new EORTC/MSGERC ICU working group criteria had high specificity (0.59 [0.41-0.75]) and sensitivity (0.73 [0.59-0.85]). CONCLUSIONS: In a cohort of mixed ICU patients, the agreement among four algorithms for the diagnosis of IPA was low. Although improved by the latest diagnostic criteria, the discrimination of invasive fungal infection from Aspergillus colonisation in critically ill patients remains challenging and requires further optimization.

Hepatic Vasculopathy and Regenerative Responses of the Liver in Fatal Cases of COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects the nasopharynx and lungs and causes coronavirus disease-2019 (COVID-19). It may impact the heart, brain, kidney, and liver.1 Although functional impairment of the liver has been correlated with worse clinical outcomes, little is known about the pathophysiology of hepatic injury and repair in COVID-19.2,3 Histologic evaluation has been limited to small numbers of COVID-19 cases with no control subjects2,4 and demonstrated largely heterogeneous patterns of pathology.2,3.

Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study.

BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. RESULTS: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.

[Toxicity after chimeric antigen receptor T-cell therapy : Overview and management of early and late onset side effects]. / Toxizitäten nach Chimärer-Antigenrezeptor-T-Zell-Therapie : Übersicht und Management früher und verzögerter Nebenwirkungen.

BACKGROUND: The transfusion of chimeric antigen receptor (CAR) T­cells has become established as a new treatment option in oncology; however, this is regularly associated with immune-mediated side effects, which can also run a severe course and necessitate a specific treatment and intensive medical treatment. MATERIAL AND METHODS: A literature review was carried out on CAR T-cell therapy, toxicities and the management of side effects. RESULTS: The cytokine release syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS) regularly occur shortly after CAR T-cell treatment. The symptoms of CRS can range from mild flu-like symptoms to multiorgan failure. In addition to mild symptoms, such as disorientation and aphasia, ICANS can also lead to convulsive seizures and brain edema. The management of CRS and ICANS is based on the severity according to the grading of the American Society for Transplantation and Cellular Therapy (ASTCT). Tocilizumab and corticosteroids are recommended for CRS and corticosteroids are used for ICANS. In the further course persisting hypogammaglobulinemia and cytopenia are frequent even months after the initial treatment and promote infections even months after CAR T­cell therapy. DISCUSSION: Potentially severe complications regularly occur after CAR T-cell therapy. An interdisciplinary cooperation between intensive care physicians, hematologists, neurologists and specialists in other disciplines is of decisive importance for the optimal care of patients after CAR T­cell therapy.

[Management of seasonal influenza in 2017/2018 at a German tertiary-care hospital]. / Management der saisonalen Influenza 2017/2018: Erfahrungen an einem deutschen Universitätsklinikum.

BACKGROUND: There are only few structured reports on inpatient management of a seasonal influenza epidemic. OBJECTIVES: A systematic description of a seasonal influenza patient population at a German university hospital to improve risk stratification and clinical care. METHODS: In this monocentric, retrospective observational study of the 2017/2018 influenza season at the University Medical Center Hamburg-Eppendorf, patients with confirmed influenza infection were included. RESULTS: Of all influenza swabs performed in the emergency department, 24% (n = 162/676) were positive. A total of 255 patients (median age 66 years) had an influenza infection (influenza A n = 79, influenza B n = 176); 27 (15.3%) were nosocomial infections. Of the 179 (70.2%) patients that were hospitalized, 51 (20%) received intensive medical care. Patients with subsequent need for intensive care had an elevated CRP level (69.5 mg/dl [SD 62.8] vs. 141.7 [SD 127.2] mg/dl) at the time of influenza diagnosis and more frequent infiltrates in X­ray/CT of the thorax (n = 43 [33.6%] vs. n = 43 [84.3%]). Antiviral therapy with oseltamivir was administered for 74 (29.0%) patients and 11 (6.1%) patients were treated with extracorporeal membrane oxygenation (ECMO). Of the 23 (9.0%) patients who died, only four of them had been vaccinated (trivalent). Those four had an influenza B infection. CONCLUSION: The structured use of diagnostic tests (influenza PCR, X­ray/CT chest and CRP) and antiviral therapy (oseltamivir) as well as targeted management of admission, intensive care capacities, and an increase in vaccination rates are important for improving patient care and optimizing the use of resources during seasonal influenza epidemics.

Efficacy of introducing a checklist to reduce central venous line associated bloodstream infections in the ICU caring for adult patients.

BACKGROUND: Central line-associated bloodstream infections (CLABSI) are a major source of sepsis in modern intensive care medicine. Some years ago bundle interventions have been introduced to reduce CLABSI. The use of checklists may be an additional tool to improve the effect of these bundles even in highly specialized institutions. In this study we investigate if the introduction of a checklist reduces the frequency of CLABSI. METHODS: During the study period from October 2011 to September 2012, we investigated the effect of implementing a checklist for the placement of central venous lines (CVL). Patients were allocated either to the checklist group or to the control group, roughly in a 1:2 ratio. The frequency of CLABSI was compared between the two groups. RESULTS: During the study period 4416 CVL were inserted; 1518 in the checklist group and 2898 in the control group. The use of the checklist during CVL placement resulted in a lower CLABSI frequency. The incidence in the checklist group was 3.8 per 1000 catheter days as compared to 5.9 per 1000 catheter days in the control group (IRR = 0.57; p = 0.001). The use of the checklist also reduced the frequency of catheter colonisation significantly, 36.3 per 1000 catheter days in the checklist group vs 21.2 per 1000 catheter days in the control group, respectively (IRR = 0.58; p < 0.001). CONCLUSION: The introduction of a checklist to improve the adherence to hygiene standards while placement of central venous lines reduced the frequency of infections significantly.

A case of severe Ebola virus infection complicated by gram-negative septicemia.

Ebola virus disease (EVD) developed in a patient who contracted the disease in Sierra Leone and was airlifted to an isolation facility in Hamburg, Germany, for treatment. During the course of the illness, he had numerous complications, including septicemia, respiratory failure, and encephalopathy. Intensive supportive treatment consisting of high-volume fluid resuscitation (approximately 10 liters per day in the first 72 hours), broad-spectrum antibiotic therapy, and ventilatory support resulted in full recovery without the use of experimental therapies. Discharge was delayed owing to the detection of viral RNA in urine (day 30) and sweat (at the last assessment on day 40) by means of polymerase-chain-reaction (PCR) assay, but the last positive culture was identified in plasma on day 14 and in urine on day 26. This case shows the challenges in the management of EVD and suggests that even severe EVD can be treated effectively with routine intensive care.

Emergence of ceftazidime/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate.

Background: Avibactam is a novel broad-range ß-lactamase inhibitor active against Ambler class A (including ESBL and KPC) and some Ambler class C and D (e.g. OXA-48) enzymes. We here report on the emergence of ceftazidime/avibactam resistance in clinical, multiresistant, OXA-48 and CTX-M-14-producing Klebsiella pneumoniae isolate DT12 during ceftazidime/avibactam treatment. Methods and results: Comparative whole-genome sequence analysis identified two SNPs in the CTX-M-14-encoding gene leading to two amino acid changes (P170S and T264I). Compared with WT CTX-M-14, expression of the CTX-M-14Δ170Δ264 isoform in Escherichia coli led to a >64- and 16-fold increase in ceftazidime and ceftazidime/avibactam MICs, respectively, functionally linking the observed SNPs and elevated MICs. The mutated CTX-M-14 isoform exhibited augmented ceftazidime hydrolytic activity, which was a reasonable cause for impaired susceptibility to avibactam inhibition. The P170S exchange in CTX-M-14 was found in association with elevated ceftazidime/avibactam MICs for independent K. pneumoniae isolates, but was not sufficient for full resistance. Apparently, additional CTX-M-independent mechanisms contribute to ceftazidime/avibactam resistance in K. pneumoniae DT12. Conclusions: This study on the molecular basis of ceftazidime/avibactam resistance in clinical K. pneumoniae emerging in vivo underscores the need for continuous monitoring of ceftazidime/avibactam susceptibility during therapy. Despite sustained inhibition of OXA-48, rapid development of CTX-M-14 isoforms exhibiting augmented ceftazidime hydrolytic activity may limit the usefulness of ceftazidime/avibactam monotherapies in infections caused by isolates carrying blaCTX-M-14 and blaOXA-48.

Risk factors for excessively prolonged meropenem use in the intensive care setting: a case-contol study.

BACKGROUND: Inappropriate use of broad-spectrum antimicrobials affects adversely both the individual patient and the general public. The aim of the study was to identify patients at risk for excessively prolonged carbapenem treatment in the ICU as a target for antimicrobial stewardship interventions. METHODS: Case-control study in a network of 11 ICUs of a university hospital. Patients with uninterrupted meropenem therapy (MT) > 4 weeks were compared to controls. Controls were defined as patients who stayed on the ICU > 4 weeks and received meropenem for ≤ 2 weeks. Associations between case-control status and potential risk factors were determined in a multivariate logistic regression model. RESULTS: Between 1st of January 2013 and 31st of December 2015, we identified 36 patients with uninterrupted MT > 4 weeks. Patients with prolonged MT were more likely to be surgical patients (72.2% of cases vs. 31.5% of controls; p ≤ 0.001) with peritonitis being the most common infection (n = 16, 44.4%). In the multivariate logistic regression model colonization with multidrug-resistant (MDR) Gram-negative bacteria (OR 7.52; 95% CI 1.88-30.14, p = 0.004) and the type of infection (peritonitis vs. pneumonia: OR 16.96, 95% CI 2.95-97.49) were associated with prolonged MT. CONCLUSION: Surgical patients with peritonitis and patients with known colonization with MDR Gram-negative bacteria are at risk for excessively prolonged carbapenem therapy and represent an important target population for antimicrobial stewardship interventions.