Disease- and Medication-Specific Differences of the Microbial Spectrum in Perianal Fistulizing Crohn's Disease-Relevant Aspects for Antibiotic Therapy.

Perianal fistulizing Crohn's Disease (CD) with abscess formation represents an aggressive phenotype in Inflammatory Bowel Disease (IBD) with increased morbidity. Treatment is multidisciplinary and includes antibiotics, but knowledge about the microbial spectrum is rare often resulting in inadequate antimicrobial therapy. In this single center retrospective study, all patients who were operated due to perianal abscess formation were retrospectively analyzed and the microbial spectrum evaluated. Patients were divided into a CD and non-CD group with further subgroup analysis. 138 patients were finally included in the analysis with 62 patients suffering from CD. Relevant differences were detected for the microbial spectrum with anaerobic bacteria being significantly more often isolated from non-CD patients. In a subgroup-analysis of CD patients only, medical therapy had a relevant effect on the microbial spectrum since Streptococcus groups and Enterobacterales were significantly more often isolated in patients treated with steroids compared to those being treated by antibodies. In conclusion, the microbial spectrum of patients suffering from CD varies significantly from non-CD patients and immunosuppressive medication has a relevant effect on isolated pathogens. Based on that, adaption of antibiotic treatment might be discussed in the future.

Microbial Spectrum and Antibiotic Resistance in Patients Suffering from Penetrating Crohn's Disease.

Intraabdominal abscess formation occurs in up to 30% of patients suffering from Crohn´s disease (CD). While international guidelines recommend a step-up approach with a combination of empiric antibiotic therapy and percutaneous drainage to delay or even avoid surgery, evidence about microbial spectrum in penetrating ileitis is sparse. We retrospectively assessed outcomes of 46 patients with terminal penetrating Ileitis where microbial diagnostics have been performed and compared microbial spectrum and antibiotic resistance profile of CD patients with patients suffering from diverticulitis with intraabdominal abscess formation. In both groups, the most frequently isolated pathogen was the gram-negative bacterium E.coli belonging to the family of Enterobacterales. However, overall Enterobacterales were significantly more often verifiable in the control group than in CD patients. Furthermore, microbial analysis showed significant differences regarding isolation of anaerobic pathogens with decreased frequency in patients with CD. Subgroup analysis of CD patients to evaluate a potential influence of immunosuppressive therapy on microbial spectrum only revealed that Enterobacterales was less frequently detected in patients treated with steroids. Immunosuppressive therapy did not show any impact on all other groups of pathogens and did not change antibiotic resistance profile of CD patients. In conclusion, we were able to demonstrate that the microbial spectrum of CD patients does differ only for some pathogen species without increased rate of antibiotic resistance. However, the empiric antibiotic therapy for CD-associated intra-abdominal abscess remains challenging since different points such as local epidemiological and microbiological data, individual patient risk factors, severity of infection, and therapy algorithm including non-surgical and surgical therapy options should be considered before therapeutical decisions are made.

Comparison of Duration and Empiric Antibiotic Choice of Post-Operative Treatment in Abdominal Sepsis.

Background: Although abdominal foci are the second most common source of sepsis, only few studies focus on the optimal length of post-operative antibiotic therapy in critically ill patients with abdominal sepsis. The aim of this study was to compare the outcomes of short versus long antibiotic therapy as well as broad-spectrum penicillin versus carbapenem in patients with abdominal sepsis. Patients and Methods: We performed a single center retrospective study in patients with abdominal sepsis who underwent emergency surgery. The study was conducted in a tertiary hospital in Germany during 2016-2018. We reviewed the duration of post-operative antibiotic therapy and the initially used agent, comparing patients treated shorter or longer than seven days with or without source control. Depending on the empirically given antibiotic, a subgroup analysis was conducted comparing patients treated with piperacillin-tazobactam versus carbapenems. Results: Longer duration of post-operative antibacterial treatment (>7 days) was not substantially advantageous. The group with a longer course of antibiotic therapy had more severe post-operative complications (82.4% [n = 61] vs. 62.5% [n = 20]; p = 0.01) requiring longer critical care support (18 days vs. 11 days; p = 0.027), prolonging the length of stay (28 days vs. 20 days; p = 0.044). Surgical re-interventions were more frequent in the long-course arm (70.3% vs. 40.6%; p = 0.004). The subgroup analysis comparing piperacillin-tazobactam versus carbapenems confirmed more severe complications (86.3% vs. 67.5%; p = 0.04) for the carbapenem arm. Conclusions: Post-surgical continuation of antibiotic agents beyond seven days was observed with more post-operative complications and delayed recovery. Piperacillin-tazobactam seems to be a potent alternative for patients with abdominal sepsis.

Cefazolin Might Be Adequate for Perioperative Antibiotic Prophylaxis in Intra-Abdominal Infections without Sepsis: A Quality Improvement Study.

BACKGROUND: The adequate choice of perioperative antibiotic prophylaxis (PAP) could influence the risk of surgical site infections (SSIs) in general surgery. A new local PAP guideline was implemented in May 2017 and set the first-generation cefazolin (CFZ) instead the second-generation cefuroxime (CXM) as the new standard prophylactic antibiotic. The aim of this study was to compare the risk of SSIs after this implementation in intra-abdominal infections (IAIs) without sepsis. METHODS: We performed a single center-quality improvement study at a 1500 bed sized university hospital in Germany analyzing patients after emergency surgery during 2016 to 2019 (n = 985), of which patients receiving CXM or CFZ were selected (n = 587). Propensity score matching was performed to ensure a comparable risk of SSIs in both groups. None-inferiority margin for SSIs was defined as 8% vs. 4%. RESULTS: Two matched cohorts with respectively 196 patients were compared. The rate of SSIs was higher in the CFZ group (7.1% vs. 3.6%, p = 0.117) below the non-inferiority margin. The rate of other postoperative infections was significantly higher in the CFZ group (2.0% vs. 8.7%, p = 0.004). No other differences including postoperative morbidity, mortality or length-of-stay were observed. CONCLUSION: Perioperative antibiotic prophylaxis might be safely maintained by CFZ even in the treatment of intra-abdominal infections.

Combined Training Intervention Targeting Medical and Nursing Staff Reduces Ciprofloxacin Use and Events of Urinary Tract Infection.

Inappropriate diagnosis of urinary tract infections (UTI) contributes to antimicrobial overuse. A combined training intervention for medical and nursing staff mainly addressing the analytic process reduced UTI events (9.20 vs. 7.36 per 1000 PD, -20.0%, p = 0.003) and the utilization rate of ciprofloxacin (11.6 vs. 3.5, -69.6 p = 0.001) in a Bavarian University Hospital. Combined training intervention-as part of an antibiotic stewardship program-can be effective in avoiding unnecessary urinalysis and reducing antibiotic consumption.

Retrospective Cohort Analysis of the Effect of Antimicrobial Stewardship on Postoperative Antibiotic Therapy in Complicated Intra-Abdominal Infections: Short-Course Therapy Does Not Compromise Patients' Safety.

BACKGROUND: Recent evidence suggests that short-course postoperative antibiotic therapy (PAT) of intra-abdominal infections is non-inferior considering clinical outcomes. The aim of this study was to compare the outcome of short vs. long PAT in complicated intra-abdominal infections (cIAIs) without sepsis. METHODS: We performed a single center-quality improvement study at a 1500 bed sized university hospital in Bavaria, Germany, with evaluation of the length of antibiotic therapy after emergency surgery on cIAIs with adequate source control during 2016 to 2018. We reviewed a total of 260 cases (160 short duration vs. 100 long duration). The antibiotic prescribing quality was assessed by our in-house antimicrobial stewardship team (AMS). RESULTS: No significant differences of patient characteristics were observed between short and long PAT. The frequency of long PAT declined during the observation period from 48.1% to 26.3%. Prolongation of PAT was not linked with any clinical benefits, on the contrary clinical outcome of patients receiving longer regimes were associated with higher postoperative morbidity. AMS identified additional educational targets to improve antibiotic prescribing quality on general wards like unnecessary postoperative switches of antibiotic regimes, e.g., unrequired switches to oral antibiotics as well as prolongation of PAT due to elevated CRP. CONCLUSION: Short-course antibiotic therapy after successful surgical source control in cIAIs is safe, and long-duration PAT has no beneficial effects.

Antimicrobial stewardship measures in cardiac surgery and its impact on surgical site infections.

OBJECTIVE: The goal of this study was to monitor the compliance and impact on a protocol change of surgical antimicrobial prophylaxis in cardiac surgery favouring cefazolin instead cefuroxime, initiated by the hospital's antimicrobial stewardship team. METHODS: This quality improvement study was performed in a tertiary care hospital in collaboration with the department of cardiothoracic surgery and the hospitals antimicrobial stewardship team following a revision of the standard for surgical antimicrobial prophylaxis including 1029 patients who underwent cardiac surgery. 582 patients receiving cefuroxime and 447 patients receiving cefazolin respectively were compared without altering any other preventative perioperative measures including its postoperative duration of less than 24 h. Adherence and surgical site infections were compiled and analysed. RESULTS: A complete adherence was achieved. Overall surgical site infections occurred in 37 (3.6%) of the cases, 20 (3.4%) in cefuroxime patients and 17 (3.8%) in cefazolin patients (p value = 0.754). No statistically significant differences could be found in any of the primary endpoints, but there was a trend towards less deep sternal wound infections in the cefazolin group. CONCLUSIONS: The study supports the role of antimicrobial stewardship in cardiac surgery and mirrors the success of a multidisciplinary team aiming to minimize adverse events by optimizing antibiotic use.

Defining the Scope of Antimicrobial Stewardship Interventions on the Prescription Quality of Antibiotics for Surgical Intra-Abdominal Infections.

BACKGROUND: The aim of this study was to assess the impact of antimicrobial stewardship interventions on surgical antibiotic prescription behavior in the management of non-elective surgical intra-abdominal infections, focusing on postoperative antibiotic use, including the appropriateness of indications. METHODS: A single-center quality improvement study with retrospective evaluation of the impact of antimicrobial stewardship measures on optimizing antibacterial use in intra-abdominal infections requiring emergency surgery was performed. The study was conducted in a tertiary hospital in Germany from January 1, 2016, to January 30, 2020, three years after putting a set of antimicrobial stewardship standards into effect. RESULTS: 767 patients were analyzed (n = 495 in 2016 and 2017, the baseline period; n = 272 in 2018, the antimicrobial stewardship period). The total days of therapy per 100 patient days declined from 47.0 to 42.2 days (p = 0.035). The rate of patients receiving postoperative therapy decreased from 56.8% to 45.2% (p = 0.002), comparing both periods. There was a significant decline in the rate of inappropriate indications (17.4% to 8.1 %, p = 0.015) as well as a significant change from broad-spectrum to narrow-spectrum antibiotic use (28.8% to 6.5%, p ≤ 0.001) for postoperative therapy. The significant decline in antibiotic use did not affect either clinical outcomes or the rate of postoperative wound complications. CONCLUSIONS: Postoperative antibiotic use for intra-abdominal infections could be significantly reduced by antimicrobial stewardship interventions. The identification of inappropriate indications remains a key target for antimicrobial stewardship programs.

Sterile protection against human malaria by chemoattenuated PfSPZ vaccine.

A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ ('PfSPZ Vaccine'); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine or mefloquine (chemoprophylaxis with sporozoites). We assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ ('PfSPZ Challenge') to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZ-CVac). Three doses of 5.12 × 104 PfSPZ of PfSPZ Challenge at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III). Protective efficacy was dependent on dose and regimen. Immunization with 3.2 × 103 (group I) or 1.28 × 104 (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively. Three doses of 5.12 × 104 PfSPZ at five-day intervals protected 5 out of 8 (63%) volunteers. The frequency of Pf-specific polyfunctional CD4 memory T cells was associated with protection. On a 7,455 peptide Pf proteome array, immune sera from at least 5 out of 9 group III vaccinees recognized each of 22 proteins. PfSPZ-CVac is a highly efficacious vaccine candidate; when we are able to optimize the immunization regimen (dose, interval between doses, and drug partner), this vaccine could be used for combination mass drug administration and a mass vaccination program approach to eliminate malaria from geographically defined areas.

Rapid real-time PCR for detection of Mycobacterium tuberculosis complex DNA in formalin-fixed paraffin embedded tissues: 16% of histological 'sarcoid' may contain such DNA.

AIMS: To investigate the diagnostic accuracy of IS6110 real-time PCR for detection of Mycobacterium tuberculosis complex (MTBC) in DNA extracted from formalin-fixed paraffin embedded (FFPE) tissues using two different methods. In the absence of material submitted for tuberculosis (TB) culture, MTBC detection in FFPE tissue can be an important aid to diagnosis. METHODS: We collected 144 FFPE tissue blocks (lung and lymph node) for IS6110 real-time PCR. Two DNA extraction methods (QIAamp FFPE tissue kit and NucliSENS easyMAG) were assessed within a general laboratory setting. PCR results were compared with histology and culture. RESULTS: In the histological MTBC and culture MTBC (TB-positive) groups, 72.4% were IS6110-positive and 27.6% negative. IS6110-negative results were obtained from 98%, 61.5% and 84% of the histologically MTBC-negative (TB-negative) group, histologically TB/no culture group and sarcoidosis group, respectively. Review of 19 IS6110-positive patients in the latter three groups showed that 15 had clinical TB. Thirteen of 15 (86.7%) IS6110-positive patients in the histological TB/no culture group and 2 of 4 (50%) IS6110-positive patients in the sarcoidosis group were clinically diagnosed with TB which highlights the difficulty of a pathological diagnosis. CONCLUSIONS: IS6110 real-time PCR using easyMAG extracted DNA is a moderately sensitive, specific and rapid method for MTBC detection in FFPE material, but must be interpreted in the overall clinical context. PCR results can be available in around 5 h from FFPE specimen receipt, with minimal hands-on time.

Screening of Hepatitis G and Epstein-Barr Viruses Among Voluntary non Remunerated Blood Donors (VNRBD) in Burkina Faso, West Africa.

In most sub-Saharan countries screening of blood-transmitted infections includes mainly HIV, HBV, HCV and syphilis. Many viruses such as Hepatitis G (HGV) and Epstein-Barr virus (EBV) which also carry a risk of transmission by blood transfusion raise the question of the extent of screening for these pathogens. This work aims to evaluate the prevalence of HGV and EBV in first-time blood donors in Ouagadougou. The prevalence of HGV and EBV in 551 blood donors was 7.4% and 5.4% respectively. HGV prevalence was significantly higher in blood donors with hepatitis B antigens and positive for HCV compared to donors negative for HCV and no hepatitis B antigens (respectively p<0.001 and p=0.004). EBV prevalence was higher among blood donors of < 20 years age group. HBV and HCV positive individuals are not eligible for blood donation. This study shows significant results with regard to the prevalence of HGV and EBV prevalence in blood donors in Burkina Faso and emphasizes the need for a general screening.