Publications by authors named "Johanna Kessel"

22 Publications

  • Page 1 of 1

Development and Validation of a Simplified Risk Score for the Prediction of Critical COVID-19 Illness in Newly Diagnosed Patients.

J Med Virol 2021 Jul 31. Epub 2021 Jul 31.

Department of Nephrology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Munich, Germany.

Objectives: Scores to identify patients at high risk of progression of coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may become instrumental for clinical decision-making and patient management.

Methods: We used patient data from the multicentre Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) and applied variable selection to develop a simplified scoring system to identify patients at increased risk of critical illness or death. A total of 1,946 patients who tested positive for SARS-CoV-2 were included in the initial analysis and assigned to derivation and validation cohorts (n=1,297 and n=649, respectively). Stability selection from over 100 baseline predictors for the combined endpoint of progression to the critical phase or COVID-19-related death enabled development of a simplified score consisting of five predictors: c-reactive protein (CRP), age, clinical disease phase (uncomplicated vs. complicated), serum urea, and D-dimer (abbreviated as CAPS-D score).

Results: This score yielded an area under the curve (AUC) of 0.81 [95%CI: 0.77-0.85] in the validation cohort for predicting the combined endpoint within 7 days of diagnosis and 0.81 [95%CI: 0.77-0.85] during full follow-up. We used an additional prospective cohort of 682 patients, diagnosed largely after the "first wave" of the pandemic to validate the predictive accuracy of the score and observed similar results (AUC for event within 7 days: 0.83, [95%CI: 0.78-0.87]; for full follow-up: 0.82, [95%CI: 0.78-0.86]).

Conclusion: An easily applicable score to calculate the risk of COVID-19 progression to critical illness or death was established and validated. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jmv.27252DOI Listing
July 2021

Disseminated disease due to non-tuberculous mycobacteria in HIV positive patients: A retrospective case control study.

PLoS One 2021 13;16(7):e0254607. Epub 2021 Jul 13.

Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.

Introduction: Disseminated infection due to non-tuberculous mycobacteria has been a major factor of mortality and comorbidity in HIV patients. Until 2018, U.S. American guidelines have recommended antimycobacterial prophylaxis in patients with low CD4 cell counts, a practice that has not been adopted in Europe. This study aimed at examining the impact of disseminated NTM disease on clinical outcome in German HIV patients with a severe immunodeficiency.

Materials And Methods: In this retrospective case control study, HIV patients with disseminated NTM disease were identified by retrospective chart review and matched by their CD4 cell counts to HIV patients without NTM infection in a 1:1 alocation. Primary endpoints were mortality and time to first rehospitalisation. In addition, other opportunistic diseases, as well as antimycobacterial and antiretroviral treatments were examined.

Results: Between 2006 and 2016, we identified 37 HIV patients with disseminated NTM disease. Most of them were suffering from infections due to M. avium complex (n = 31, 77.5%). Time to event analysis showed a non-significant trend to higher mortality in patients with disseminated NTM disease (p = 0.24). Rehospitalisation took place significantly earlier in patients with disseminated NTM infections (median 40.5 days vs. 109 days, p<0.0001).

Conclusion: In this retrospective case control study, we could demonstrate that mortality is not significantly higher in HIV patients with disseminated NTM disease in the ART era, but that they require specialised medical attention in the first months following discharge.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254607PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277071PMC
July 2021

Risk factors for IRIS in HIV-associated Pneumocystis-pneumonia following ART initiation.

J Infect 2021 Jul 7. Epub 2021 Jul 7.

Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, Frankfurt am Main 60590, Germany. Electronic address:

Background: HIV-infected patients with Pneumocystis-pneumonia (PCP) may develop paradoxical immune reconstitution inflammatory syndrome (IRIS), when combination antiretroviral therapy (cART) is started early during the course of PCP-treatment (PCPT). The aim of this study was to identify risk factors and predictors for PCP-IRIS and to improve individualized patient care.

Methods: An ICD-10 code hospital database query identified all Frankfurt HIV Cohort patients being diagnosed with PCP from January 2010 - June 2016. Patient charts were evaluated retrospectively for demographic, clinical and therapeutic (cART/PCPT) characteristics and incidence of paradoxical IRIS according to French's case definitions.

Results: IRIS occurred in 12/97 patients that started cART while on PCPT (12.4%). They had a higher rate of re-hospitalization (41.7vs. 4.7%; odds ratio (OR) 14.46; p = 0.009), intensive care treatment (66.7vs. 30.6%; OR = 4.54; p = 0.018), and longer median hospitalization (48 days vs. 23; p < 0.001). A high HIV-RNA level (> 6Log/ml) before cART initiation was associated with IRIS development (41.6vs. 15.0%; OR 4.05; p = 0.042). Serum immunoglobulin G-levels (IgG) [mg/dl] were lower (894.0 vs. 1446.5; p = 0.023).

Conclusion: Higher hospitalization rate and morbidity parameters underscore the clinical importance of PCP-related paradoxical IRIS. A baseline viral load of > 6Log10/ml and serum IgG may help to assess individual risks for PCP-IRIS.
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http://dx.doi.org/10.1016/j.jinf.2021.06.027DOI Listing
July 2021

The Added Value of Cerebral Imaging in Patients With Pyogenic Spinal Infection.

Front Neurol 2021 4;12:628256. Epub 2021 May 4.

Department of Neurosurgery, Goethe University Hospital, Frankfurt am Main, Germany.

The incidence of pyogenic spinal infection has increased in recent years. In addition to treatment of the spinal infection, early diagnosis and therapy of coexisting infections, especially of secondary brain infection, are important. The aim of this study is to elucidate the added value of routine cerebral imaging in the management of these patients. This was a retrospective single-center study. Cerebral imaging consisting of cerebral magnetic resonance imaging (cMRI) was performed to detect brain infection in patients with a primary pyogenic spinal infection. We analyzed a cohort of 61 patients undergoing cerebral imaging after diagnosis of primary pyogenic spinal infection. The mean age in this cohort was 68.7 years and the gender distribution consisted of 44 males and 17 females. Spinal epidural abscess was proven in 32 (52.4%) patients. Overall positive blood culture was obtained in 29 (47.5%) patients, infective endocarditis was detected in 23 (37.7%) patients and septic condition at admission was present in 12 (19.7%) Patients. Coexisting brain infection was detected in 2 (3.3%) patients. Both patients revealed clinical signs of severe sepsis, reduced level of consciousness (GCS score 3), were intubated, and died due to multi-organ failure. Brain infection in patients with spinal infection is very rare. Of 61 patients with pyogenic spinal infection, two patients had signs of cerebral infection shown by imaging, both of whom were in a coma (GCS 3), and sepsis.
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http://dx.doi.org/10.3389/fneur.2021.628256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129560PMC
May 2021

Risk factors and outcomes associated with the carriage of tigecycline- and vancomycin-resistant Enterococcus faecium.

J Infect 2021 02 4;82(2):227-234. Epub 2020 Dec 4.

University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany; Institute for Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany; University Center of Competence for Infection Control, State of Hesse, Germany. Electronic address:

Objectives: Vancomycin-resistant E. faecium (VRE) is a common cause of healthcare-associated infections. The emergence of VRE with tigecycline resistance (TVRE) is increasing but its impact on patient outcome is still not well defined. This study aimed to assess risk factors for the acquisition of TVRE and of patient outcomes associated with TVRE carriage/infection.

Methods: At the University Hospital Frankfurt, we conducted a matched pair TVRE-VRE analysis to identify risk factors for TVRE carriage. Bed-to-bed contacts and potential transmission routes were reconstructed. TVRE were whole-genome sequenced to confirm suspected transmission events and to identify tigecycline resistance mechanisms.

Results: 76 TVRE cases were identified between 02/2014-04/2017 and compared to VRE colonized or infected controls. TVRE carriage was associated with exposure to tigecycline, an increased rate of bloodstream infections (BSI) with VRE or Candida spp., and higher mortality. Whole-genome sequencing-based analysis of 24 TVRE provided evidence for transmissions of TVRE, also across different wards.

Conclusions: Tigecycline exposure is the main risk factor for TVRE carriage. VRE/TVRE- and Candida-BSI are associated with worse clinical outcome. Hospital transmission of TVRE may occur despite strict contact precautions, whereas both antimicrobial stewardship and infection control interventions are of high importance to prevent emergence and spread of TVRE.
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http://dx.doi.org/10.1016/j.jinf.2020.12.003DOI Listing
February 2021

Homograft Treatment for Infected Frozen Elephant Trunk Prosthesis.

Heart Surg Forum 2020 Oct 19;23(6):E786-E788. Epub 2020 Oct 19.

Department of General and Visceral Surgery, University Hospital Frankfurt, Frankfurt am Main, Germany.

A 46-year-old male received total arch replacement with frozen elephant trunk for acute non-A/non-B aortic dissection. Two months later, he underwent emergency reoperation for contained rupture of the left common carotid ostium at its insertion on the aortic arch. Three months after the reoperation, he developed tracheoesophageal fistula and infection of the prosthesis in the region of the aortic arch and the proximal descending aorta. Second reoperation was performed with replacement of the aorta with a composite of three aortic homografts, and the fistula was permanently closed with a direct suture and intercostal muscle flap.
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http://dx.doi.org/10.1532/hsf.3237DOI Listing
October 2020

Impact of Clostridioides difficile infection on the outcome of patients receiving a hematopoietic stem cell transplantation.

Int J Infect Dis 2020 Oct 12;99:428-436. Epub 2020 Aug 12.

University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt am Main, Germany; Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Frankfurt am Main, Germany; University Center of Competence for Infection Control, State of Hesse, Germany.

Objectives: Clostridioides difficile infections (CDI) are common in autologous (auto-HSCT) or allogenic hematopoietic stem cell transplant (allo-HSCT) recipients. However, the impact of CDI on patient outcomes is controversial. We conducted this study to examine the impact of CDI on patient outcomes.

Methods: We performed a retrospective single-center study, including 191 lymphoma patients receiving an auto-HSCT and 276 acute myeloid leukemia (AML) patients receiving an allo-HSCT. The primary endpoint was overall survival (OS). Secondary endpoints were causes of death and, for the allo-HSCT cohort, GvHD- and relapse-free survival (GRFS).

Results: The prevalence of CDI was 17.6% in the AML allo-HSCT and 7.3% in the lymphoma auto-HSCT cohort. A higher prevalence of bloodstream infections, but no differences concerning OS or cause of death were found for patients with CDI in the auto-HSCT cohort. [AU] In the allo-HSCT cohort, OS and GRFS were similar between CDI and non-CDI patients. However, the leading cause of death was relapse among non-CDI patients, but it was infectious diseases in the CDI group with fewer deaths due to relapse.

Conclusions: CDI was not associated with worse survival in patients receiving a hematopoietic stem cell transplantation, and there were even fewer relapse-related deaths in the AML allo-HSCT cohort.
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http://dx.doi.org/10.1016/j.ijid.2020.08.030DOI Listing
October 2020

Two cases of airport-associated falciparum malaria in Frankfurt am Main, Germany, October 2019.

Euro Surveill 2019 Dec;24(49)

These authors contributed equally to this work and share last authorship.

Two cases of presumably airport-acquired falciparum malaria were diagnosed in Frankfurt in October 2019. They were associated with occupation at the airport, and parasites from their blood showed genetically identical microsatellite and allele patterns. Both had severe malaria. It took more than a week before the diagnosis was made. If symptoms are indicative and there is a plausible exposure, malaria should be considered even if patients have not travelled to an endemic area.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.49.1900691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905295PMC
December 2019

The Role of Microbiota in Preventing Multidrug-Resistant Bacterial Infections.

Dtsch Arztebl Int 2019 10;116(40):670-676

Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Johann Wolfgang Goethe University, Frankfurt am Main; Department of Internal Medicine, Hematology/Oncology, University Hospital Frankfurt, Johann Wolfgang Goethe University, Frankfurt am Main; Department I of Internal Medicine, University Hospital of Cologne, Center for Integrated Oncology Aachen, Bonn, Köln, Düsseldorf; German Center for Infection Research (DZIF), Bonn-Cologne.

Background: The introduction of industrially produced antibiotics was a milestone in the history of medicine. Now, almost a century later, the adverse consequences of these highly effective drugs have become evident in the form of antibiotic-resistant infections, which are on the rise around the world. The search for solutions to this problem has involved both the introduction of newer types of antibiotics and, increasingly, the development of alternative strategies to prevent infections due to multidrug-resistant bacteria. In this article, we review the pathophysiological connection between the use of antibiotics and the occurrence of such infections. We also discuss some alternative strategies that are currently under development.

Methods: This review is based on pertinent articles that appeared from January 2000 to April 2019 and were retrieved by a selective search in the PubMed database employing the search term "(microbiota OR microbiome) AND infection." Further suggestions by our author team regarding relevant literature were considered as well.

Results: The spectrum of preventive strategies encompasses measures for the protection of the intestinal microbiota (antimicrobial stewardship, neutralization of antibiotic residues in the bowel, use of phages and species-specific antibiotics) as well as measures for its reconstitution (prebiotics, probiotics, and fecal microbiota transfer).

Conclusion: In view of the major problem that multidrug-resistant bacteria pose for the world's population and the resources now being spent on the search for a solution, derived both from public funding and from the pharmaceutical industry, we hope to see new, clinically useful approaches being developed and implemented in the near future.
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http://dx.doi.org/10.3238/arztebl.2019.0670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859878PMC
October 2019

Quinolone and Multidrug Resistance Predicts Failure of Antibiotic Prophylaxis of Spontaneous Bacterial Peritonitis.

Clin Infect Dis 2020 04;70(9):1916-1924

Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany.

Background: The efficacy of antibiotic prophylaxis to prevent spontaneous bacterial peritonitis (SBP) in patients colonized with multidrug-resistant organisms (MDROs) is unknown. We evaluated the effectiveness of fluoroquinolone-based SBP prophylaxis in an era and area of frequent antibiotic resistance.

Methods: This is a prospective observational study in patients with liver cirrhosis and an indication for fluoroquinolone-based prophylaxis of SBP. Patients were recruited and followed in a large German tertiary reference center with comprehensive microbiological and clinical monitoring performed at baseline and after 30, 60, 90, and 180 days of prophylaxis.

Results: Overall, 77 patients received antibiotic prophylaxis for an average of 93 days. Baseline prevalence of colonization with MDROs was high (N = 39, 50.6%). At least one de novo MDRO was detected in 27 patients (35.1%) during antibiotic prophylaxis; 33 patients (42.9%) developed secondary infections, including 14 cases (17.9%) of infections with MDROs, and 13 cases (16.9%) of de novo/recurrent SBP. Thirty patients (39.0%) died during follow-up. Significantly higher risks of SBP development during antibiotic prophylaxis were observed for patients with versus without any apparent MDROs (P = .009), vancomycin-resistant enterococci (P = .008), multidrug-resistant gram-negative bacteria (P = .016), or quinolone-resistant gram-negative bacteria (QR-GNB) (P = .015). In competing risk analysis, QR-GNB were independently associated with prophylaxis failure (hazard ratio, 3.39; P = .045) and infections with QR-GNB were independently associated with death before SBP (subdistribution hazard risk, 6.47; P = .034).

Conclusions: Antibiotic prophylaxis of SBP appears to be less efficient in patients with known MDROs. Regular MDRO screening seems to be useful to tailor treatment of secondary infections and re-evaluate antibiotic prophylaxis in case of selection of quinolone resistance.
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http://dx.doi.org/10.1093/cid/ciz540DOI Listing
April 2020

Intravenous and tablet formulation of posaconazole in antifungal therapy and prophylaxis: A retrospective, non-interventional, multicenter analysis of hematological patients treated in tertiary-care hospitals.

Int J Infect Dis 2019 Jun 9;83:130-138. Epub 2019 Apr 9.

University Hospital of Cologne, Department I of Internal Medicine, Cologne, Germany; German Center for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany. Electronic address:

Objectives: Novel formulations (gastro-resistant tablet and intravenous solution) of posaconazole (POS) have been approved in prophylaxis and therapy of invasive fungal diseases (IFDs). Study aim was to analyze treatment strategies and clinical effectiveness.

Methods: We set up a web-based registry on www.ClinicalSurveys.net for documentation of comprehensive data of patients who received novel POS formulations. Data analysis was split into two groups of patients who received novel POS formulations for antifungal prophylaxis (posaconazole prophylaxis group) and antifungal therapy (posaconazole therapy group), respectively.

Results: Overall, 180 patients (151 in the posaconazole prophylaxis group and 29 in the posaconazole therapy group) from six German tertiary care centers and hospitalized between 05/2014 - 03/2016 were observed. Median age was 58 years (range: 19 - 77 years) and the most common risk factor for IFD was chemotherapy (n = 136; 76%). In the posaconazole prophylaxis group and posaconazole therapy group, median POS serum levels at steady-state were 1,068 μg/L (IQR 573-1,498 μg/L) and 904 μg/L (IQR 728-1,550 μg/L), respectively (P = 0.776). During antifungal prophylaxis with POS, nine (6%) probable/proven fungal breakthroughs were reported and overall survival rate of hospitalization was 86%. The median overall duration of POS therapy was 18 days (IQR: 7 - 23 days). Fourteen patients (48%) had progressive IFD under POS therapy, of these five patients (36%) died related to or likely related to IFD.

Conclusions: Our study demonstrates clinical effectiveness of antifungal prophylaxis with novel POS formulations. In patients treated for possible/probable/proven IFD, we observed considerable mortality in patients receiving salvage treatment and with infections due to rare fungal species.
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http://dx.doi.org/10.1016/j.ijid.2019.04.006DOI Listing
June 2019

Bloodstream infections with vancomycin-resistant enterococci are associated with a decreased survival in patients with hematological diseases.

Ann Hematol 2019 Mar 21;98(3):763-773. Epub 2019 Jan 21.

Department of Hematology and Oncology, University Hospital Frankfurt, Frankfurt am Main, Germany.

Enterococcus species are commensals of the human gastrointestinal tract with the ability to cause invasive infections. For patients with hematological diseases, enterococcal bloodstream infections (BSI) constitute a serious clinical complication which may even be aggravated if the pathogen is vancomycin-resistant. Therefore, we analyzed the course of BSI due to vancomycin-susceptible enterococci (VSE) in comparison to vancomycin-resistant enterococci (VRE) on patient survival. In this retrospective single-center study, BSI were caused by VRE in 47 patients and by VSE in 43 patients. Baseline patient characteristics were similar in both groups. Concerning infection-related characteristics, an increased CRP value and an increased rate of prior colonization with multidrug-resistant organisms were detected in the VRE BSI group. More enterococcal invasive infections were found in the VSE group. The primary endpoint, overall survival (OS) at 30 days after BSI, was significantly lower in patients with VRE BSI compared to patients with VSE BSI (74.5% vs. 90.7%, p = 0.039). In a multivariate regression analysis, VRE BSI and a Charlson comorbidity index higher than 4 were independent factors associated with 30-day mortality. Moreover, we found that VRE with an additional teicoplanin resistance showed a trend towards an even lower OS.
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http://dx.doi.org/10.1007/s00277-019-03607-zDOI Listing
March 2019

Timepoints of vancomycin-resistant Enterococcus colonization predict outcomes of acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplantation.

Eur J Haematol 2018 Jul 26. Epub 2018 Jul 26.

Department of Hematology and Oncology, University Hospital Frankfurt, Frankfurt am Main, Germany.

Background: In hematology and oncology, in particular in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT), vancomycin-resistant Enterococcus spp. (VRE) colonization rates are high due to previous hospital stays and preceding antibiotic treatment and colonized patients have a lower overall survival (OS).

Objective: We reanalyzed our previously published cohort, to unravel which colonization timepoints before and during allo-HSCT might be predictive for the subsequent outcome.

Patients And Methods: We report about 268 patients with acute myeloid leukemia receiving an allo-HSCT between 2006 and 2016.

Results: We identified 129 never-colonized patients, 15 previously colonized patients (positive only before admission for allo-HSCT), 41 persistently colonized patients (positive before and at admission for allo-HSCT), and 83 newly colonized patients (positive only during allo-HSCT). Persistently and newly colonized patients had a worse 60 months OS due to increased incidence of non-relapse-related mortality (NRM) than never-colonized patients (OS: never-colonized: 61.0% vs persistently colonized: 43.5%; P = 0.023 vs newly colonized: 45.6%; P = 0.046). In contrast, OS and NRM of never-colonized and previously colonized patients as well as between persistently and newly colonized patients were similar.

Conclusion: Patients can lose their VRE colonization status and acquisition of VRE during inpatient stay for allo-HSCT decreases survival to a similar extend as persistent colonization.
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http://dx.doi.org/10.1111/ejh.13151DOI Listing
July 2018

Stenotrophomonas maltophilia colonization during allogeneic hematopoietic stem cell transplantation is associated with impaired survival.

PLoS One 2018 19;13(7):e0201169. Epub 2018 Jul 19.

Department of Hematology and Oncology, Johann Wolfgang Goethe University of Frankfurt, Frankfurt am Main, Germany.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers potential cure to acute myeloid leukemia (AML) patients. However, infections with commensal bacteria are an important cause for non-relapse mortality (NRM). We have previously described the impact of multidrug-resistant organism (MDRO) colonization on the survival of allo-HSCT patients. In the aforementioned publication, according to consensus, we there did not consider the opportunistic gram-negative bacterium Stenotrophomonas maltophilia (S. maltophilia) to be an MDRO. Since rate of S. maltophilia colonization is increasing, and it is not known whether this poses a risk for allo-HSCT patients, we here analyzed here its effect on the previously described and now extended patient cohort. We report on 291 AML patients undergoing allo-HSCT. Twenty of 291 patients (6.9%) were colonized with S. maltophilia. Colonized patients did not differ from non-colonized patients with respect to their age, remission status before allo-HSCT, donor type and HSCT-comorbidity index. S. maltophilia colonized patients had a worse overall survival (OS) from 6 months up to 60 months (85% vs. 88.1% and 24.7% vs. 59.7%; p = 0.007) due to a higher NRM after allo-HSCT (6 months: 15% vs. 4.8% and 60 months: 40.1% vs. 16.2% p = 0.003). The main cause of mortality in colonized patients was infection (46.2% of all deaths) and in non-colonized patients relapse (58.8% of all deaths). 5/20 colonized patients developed an invasive infection with S. maltophilia. The worse OS after allo-HSCT due to higher infection related mortality might implicate the screening of allo-HSCT patients for S. maltophilia and a closer observation of colonized patients as outpatients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201169PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053200PMC
January 2019

Bloodstream infections with gram-negative organisms and the impact of multidrug resistance in patients with hematological malignancies.

Ann Hematol 2018 Nov 4;97(11):2225-2234. Epub 2018 Jul 4.

Department of Hematology and Oncology, University Hospital Frankfurt, Frankfurt am Main, Germany.

Infections and especially blood stream infections (BSI) with gram-negative bacteria (GNB) represent a major threat for patients with hematological diseases undergoing chemotherapy and mainly contribute to morbidity and mortality. In this retrospective single-center study, we analyzed the impact of BSI with different gram-negative multidrug-resistant bacteria (MDRGN) compared to BSI with antibiotic susceptible gram-negative bacteria. Data of 109 patients with hematological malignancies and GNB BSI were analyzed with overall survival (OS) 30 days after BSI being the primary endpoint. BSI with non-fermentative gram-negative bacteria were found in 26.6% of all patients and 73.4% suffered from a BSI with an Enterobacteriaceae. Thirty-two of 109 patients suffered from BSI with MDRGN. Characteristics of MDRGN and non-MDRGN BSI patients did not differ besides the fact that significantly more patients received an immunosuppressive therapy in the MDRGN BSI group. OS (30 days after BSI) of patients with MDRGN BSI was significantly lower (85.6 vs. 55.9%; p < 0.001) compared to patients with non-MDRGN BSI. Patients with MDRGN BSI with non-fermentative pathogens had a worse OS after 30 days compared to MDRGN BSI with Enterobacteriaceae and the same holds true for non-MDRGN BSI. In multivariate analysis of MDRGN BSI, non-fermenters and ICU admission were independently associated with increased 30-day mortality. Our data demonstrate the negative impact of non-fermentative gram-negative pathogens causing BSI compared to Enterobacteriaceae in hematological patients and thereby underlining the heterogeneity of gram-negative BSI.
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http://dx.doi.org/10.1007/s00277-018-3423-5DOI Listing
November 2018

[Piperacillin/Tazobactam Shortage: Central Restriction and Alternative Recommendations as Effective Antibiotic-Stewardship Intervention at a Maximal Care Hospital].

Dtsch Med Wochenschr 2018 Apr 13;143(8):e59-e67. Epub 2017 Dec 13.

Schwerpunkt Infektiologie, Medizinische Klinik II, Universitätsklinikum Frankfurt, Goethe-Universität.

Background:  Drug supply bottleneck is a worldwide challenge, e. g. the antibiotics Piperacillin/Tazobactam shortage in 2016/2017. The efficacy of an appropriate replacement management was evaluated at the University Hospital Frankfurt (UHF).

Methods:  The Antibiotic-Stewardship (ABS)-Team at UHF decreed a restriction of PIP/TAZ and provided alternative antibiotic therapy recommendations during the shortage period. Consequences of this intervention on antibiotic consumption and overall costs were investigated.

Results:  Over 12-weeks, PIP/TAZ-mean application rate was reduced by 71 % and was predominantly used to treat hospital acquired pneumonia (62 %), febrile neutropenian children (12 %), followed by other indications (< 10 %, each). Alternative substances' use increased (Ceftazidim + 229 %, Imipenem/Cilastatin + 18 %, Meropenem + 27 %, Ceftriaxon + 26 %, Levofloxacin + 11 %, Ciprofloxacin + 14 %, Ampicillin/Sulbactam + 83 %), however the overall antibiotic consumption declined by -5.8 % (cost savings: 13 %). Simultaneously, additional personnel costs have been noted (+ 4300 €). The evidence rate of bloodstream infections with resistant bacteria and detection of Clostridium-difficile-toxin were both not significantly elevated, compared to windows just ahead, after and one year before intervention period.

Conclusion:  Drug shortages challenge hospital antibiotic-stewardship programs by enforced use of broad spectrum-antibiotics, endanger patient safety and require rational replacement strategies, following infectious diseases- and microbiological outlines. Whilst personnel expenditures are higher, antimicrobial-stewardship interventions may successfully contribute to prevent additional medication costs.
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http://dx.doi.org/10.1055/s-0043-122706DOI Listing
April 2018

A Comparison of Aspergillus and Mucorales PCR Testing of Different Bronchoalveolar Lavage Fluid Fractions from Patients with Suspected Invasive Pulmonary Fungal Disease.

J Clin Microbiol 2018 02 24;56(2). Epub 2018 Jan 24.

Medizinische Klinik und Poliklinik II, University Hospital Würzburg, Würzburg, Germany

In patients with hematological malignancies, bronchoalveolar lavage fluid (BALF) specimens are commonly used for the diagnosis of mold infections. However, it is not clear whether the cell pellet (P) or the supernatant fraction (S) of the BALF specimen is optimal for molecular diagnostic testing. Thus, 99 BALF specimens were collected from 96 hematology patients with or without allogeneic hematopoietic stem cell transplant. The cell pellets and supernatants were processed alone and in combination (S/P) for testing by two fungus-specific real-time PCR assays compliant with international recommendations. The results achieved with S/P were revealed to be superior in comparison to those achieved with S and P alone, with the use of each single fraction showing a reduced sensitivity for the detection of DNA (82% and 43% for S and P, respectively). In 57% of the samples, testing of the combination of S and P generated a lower quantification cycle value than testing of S or P alone. Molds would have been missed in 5 and 16 out of 28 samples if only S or P, respectively, was analyzed. No sample was positive by testing of S or P only. Similar results were obtained for the detection of Mucorales DNA in BALF specimens (reduced sensitivity of 67% and 50% for S and P, respectively). Study patients were categorized according to the current European Organization for the Research and Treatment of Cancer/Mycoses Study Group classification for invasive fungal disease (IFD), revealing that 35 patients had proven/probable IFD (36%), 47 patients had possible IFD (49%), and 14 patients had undetermined IFD (15%).
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http://dx.doi.org/10.1128/JCM.01655-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786722PMC
February 2018

Clinical impact of colonization with multidrug-resistant organisms on outcome after allogeneic stem cell transplantation in patients with acute myeloid leukemia.

Cancer 2018 01 28;124(2):286-296. Epub 2017 Sep 28.

Department of Hematology and Oncology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment option for patients with acute myeloid leukemia (AML). During transplantation, patients undergo a period of severe neutropenia, which puts them at high risk for infectious complications. However, the impact of patient colonization with multidrug-resistant organisms (MDRO) on overall survival remains unclear.

Methods: In this retrospective, single-center study, the authors analyzed data from 264 patients with AML who underwent a first allo-HSCT between January 2006 and March 2016 at their institution. Primary endpoints were overall survival and nonrelapse-related mortality.

Results: One hundred forty-two of 264 patients (53.8%) were colonized by at least 1 MDRO, mainly with vancomycin-resistant Enterococcus faecalis/faecium (n = 122). The characteristics of colonized patients did not differ from those of MDRO-negative patients with respect to median age (53.5 vs 53 years), cytogenetic risk according to European LeukemiaNet criteria, remission status before allo-HSCT (first or second complete remission: 55.7% vs 60.7%, respectively; active disease: 44.4% vs 39.3%, respectively), donor type, or hematopoietic cell transplantation-comorbidity index (HCT-CI). Compared with noncolonized patients, MDRO-positive patients had an inferior probability of survival at 5 years (43.3% vs 65.5%; P = .002), primarily because of a higher cumulative incidence of nonrelapse-related mortality (33.9% vs 9.4%; P < .001). Death caused by infections occurred in 15.5% of colonized patients versus 4.9% of noncolonized patients. There was no difference in the cumulative incidence of relapse in MDRO-positive versus MDRO-negative patients (33.8% vs 42.1%, respectively; P = .798).

Conclusions: The current data emphasize the importance of regular MDRO screenings and prompt further investigations into the impact of colonization with MDRO on the immune system after allo-HSCT. Cancer 2018;124:286-96. © 2017 American Cancer Society.
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http://dx.doi.org/10.1002/cncr.31045DOI Listing
January 2018

The role of Enterococcus spp. and multidrug-resistant bacteria causing pyogenic liver abscesses.

BMC Infect Dis 2017 06 26;17(1):450. Epub 2017 Jun 26.

Department of Internal Medicine 1, University Hospital Frankfurt, Frankfurt am Main, Germany.

Background: Pyogenic liver abscesses (PLA) remain a significant clinical problem. Unfortunately, little is known about current bacterial susceptibility profiles and the incidence of multidrug resistant organisms (MDROs) causing PLA in Western countries. Yet, this crucial information is pivotal to guide empirical antibiotic therapy. Aim of this study was to provide detailed characteristics of PLA with a special focus on underlying bacterial pathogens and their susceptibility to antibiotics.

Methods: A retrospective study of patients diagnosed with PLA from 2009 to 2015 in a large tertiary reference center in Germany was performed in order to characterize PLA and antimicrobial susceptibility profiles of causative bacterial species.

Results: Overall, 86 patients were included. The most common causes of PLA were bile duct stenosis/obstruction (31.4%) and leakage of biliary anastomosis (15.1%). Frequent predisposing diseases were malignancies (34.9%), diabetes (24.4%) and the presence of liver cirrhosis (16.3%). Of note, Enterococcus spp. were the most frequently cultured bacterial isolates (28.9%), and in 1/3 of cases vancomycin resistance was observed. In addition, a relevant frequency of gram-negative MDROs was identified. In particular, an alarming 10% and 20% of gram-negative bacteria were resistant to carbapenems and tigecycline, respectively. Of note, MDRO status did not predict ICU stay or survival in multivariate regression analysis. The mortality rate in our series was 16.3%.

Conclusion: Our study demonstrates an as yet underreported role of Enterococcus spp., often associated with vancomycin resistance, as well as of gram-negative MDROs causing PLA.
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http://dx.doi.org/10.1186/s12879-017-2543-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485679PMC
June 2017

Clinical Impact of Colonization with Multidrug-Resistant Organisms on Outcome after Autologous Stem Cell Transplantation: A Retrospective Single-Center Study.

Biol Blood Marrow Transplant 2017 Sep 18;23(9):1455-1462. Epub 2017 May 18.

Department of Hematology and Oncology, Johann Wolfgang Goethe University of Frankfurt, Frankfurt am Main, Germany; University Center for Infectious Diseases, University Hospital Frankfurt, Frankfurt am Main, Germany.

A significant increase in infections caused by multidrug-resistant organisms (MDRO) has been observed in recent years, resulting in an increase of mortality in all fields of health care. Hematological patients are particularly affected by MDRO infections because of disease- and therapy-related immunosuppression. To determine the impact of colonization with MDRO on overall survival, we retrospectively analyzed data from patients undergoing autologous hematopoietic stem cell transplantation at our institution. In total, 184 patients were identified, mainly patients with lymphomas (n = 98, 53.3%), multiple myelomas (n = 80, 43.5%), germ cell cancers (n = 5, 2.7%), or acute myeloid leukemia (n = 1, .5%). Forty patients (21.7%) tested positive for MDRO colonization. At a median follow-up time of 21.5 months, the main causes of death were infection in colonized and disease progression in noncolonized patients. Nonrelapse mortality (NRM) was higher in patients who tested positive for MDRO than in the noncolonized group (25.4% versus 3%, P < .001). Interestingly, NRM in neutropenia after autologous transplantation did not differ between colonized and noncolonized patients. Colonized patients, however, had inferior overall survival after autologous transplantation in univariate (61.7% versus 73.3%, P = .005) as well as in multivariate analysis (hazard ratio, 2.463; 95% confidence interval, 1.311 to 4.626; P = .005). We conclude that the period after discharge from hospital after autologous transplantation seems critical and patients with MDRO colonization should be observed closely for infections in the post-transplantation period in outpatient care.
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http://dx.doi.org/10.1016/j.bbmt.2017.05.016DOI Listing
September 2017

Screening and contact precautions - A survey on infection control measures for multidrug-resistant bacteria in German university hospitals.

Antimicrob Resist Infect Control 2017 13;6:37. Epub 2017 Apr 13.

Department I of Internal Medicine, University Hospital of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany.

To assess the scope of infection control measures for multidrug-resistant bacteria in high-risk settings, a survey among university hospitals was conducted. Fourteen professionals from 8 sites participated. Reported policies varied largely with respect to the types of wards conducting screening, sample types used for screening and implementation of contact precautions. This variability among sites highlights the need for an evidence-based consensus of current infection control policies.
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http://dx.doi.org/10.1186/s13756-017-0191-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390437PMC
April 2017

Influence of antibiotic-regimens on intensive-care unit-mortality and liver-cirrhosis as risk factor.

World J Gastroenterol 2016 Apr;22(16):4201-10

Mireen Friedrich-Rust, Beate Wanger, Florian Heupel, Stefan Zeuzem, Joerg Bojunga, Department of Internal Medicine I (Gastroenterology, Pulmonology, Endocrinology), J.W. Goethe-University Hospital, 60590 Frankfurt, Germany.

Aim: To assess the rate of infection, appropriateness of antimicrobial-therapy and mortality on intensive care unit (ICU). Special focus was drawn on patients with liver cirrhosis.

Methods: The study was approved by the local ethical committee. All patients admitted to the Internal Medicine-ICU between April 1, 2007 and December 31, 2009 were included. Data were extracted retrospectively from all patients using patient charts and electronic documentations on infection, microbiological laboratory reports, diagnosis and therapy. Due to the large hepatology department and liver transplantation center, special interest was on the subgroup of patients with liver cirrhosis. The primary statistical-endpoint was the evaluation of the influence of appropriate versus inappropriate antimicrobial-therapy on in-hospital-mortality.

Results: Charts of 1979 patients were available. The overall infection-rate was 53%. Multiresistant-bacteria were present in 23% of patients with infection and were associated with increased mortality (P < 0.000001). Patients with infection had significantly increased in-hospital-mortality (34% vs 17%, P < 0.000001). Only 9% of patients with infection received inappropriate initial antimicrobial-therapy, no influence on mortality was observed. Independent risk-factors for in-hospital-mortality were the presence of septic-shock, prior chemotherapy for malignoma and infection with Pseudomonas spp. Infection and mortality-rate among 175 patients with liver-cirrhosis was significantly higher than in patients without liver-cirrhosis. Infection increased mortality 2.24-fold in patients with cirrhosis. Patients with liver cirrhosis were at an increased risk to receive inappropriate initial antimicrobial therapy.

Conclusion: The results of the present study report the successful implementation of early-goal-directed therapy. Liver cirrhosis patients are at increased risk of infection, mortality and to receive inappropriate therapy. Increasing burden are multiresistant-bacteria.
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http://dx.doi.org/10.3748/wjg.v22.i16.4201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837437PMC
April 2016
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