Chagas Disease: Comparison of Therapy with Nifurtimox and Benznidazole in Indigenous Communities in Colombia.

Background: For indigenous people in Colombia, high infection rates with Chagas disease (CD) are known. Methods: In 2018 and 2020, nine villages were screened for CD. CD-positive patients could enter a drug observed treatment. While, in 2018, Benznidazole (BNZ) was provided as the first-line drug by the government, nifurtimox (NFX) was administered in 2020. Results: Of 121 individuals treated with BNZ, 79 (65%) suffered from at least one adverse event (AE). Of 115 treated with NFX, at least one AE occurred in 96 (84%) patients. In 69% of BNZ cases, the side effects did not last longer than one day; this applied to 31% of NFX cases. Excluding extreme outlier values, average duration of AEs differed highly significantly: BNZ (M = 0.7, SD = 1.4) and NFX (M = 1.7, SD = 1.5, p < 0.001). Using an intensity scale, AEs were highly significantly more severe for NFX (M = 2.1, SD = 0.58) compared to BZN (M = 1.1, SD = 0.38), p < 0.001. When analyzing the duration in relation to the intensity, the burden of AEs caused by NFX was significantly more pronounced. Dropouts (n = 2) due to AEs were in the NFX-group only. Conclusions: Side effects caused by BNZ were significantly fewer, as well as milder, shorter in duration, and more easily treatable, compared to NFX.

Gastrointestinal Pathogens in Multi-Infected Individuals: A Cluster Analysis of Interaction.

Indigenous people live in remote areas of Colombia. Multiple infections with bacteria, protozoa and/or helminths are common, as well as colonization in various forms. This study focused on the question of whether and to what extent various pathogens interact with each other. Therefore, a mathematical approach was retrospectively applied to PCR-based data of 244 stool samples, collected in two datasets. A stable cluster solution of the pathogens assessed was determined, and a unique configuration between Blastocystis hominis/Campylobacter spp./Giardia lamblia forming cluster 1 and Dientaemoeba fragilis was verified. A pathogen density-dependent interplay appeared between the B. hominis/Campylobacter spp./G. lamblia cluster, D. fragilis and Ascaris lumbricoides. The applied mathematical approach demonstrated that co-infections with parasites of questionable pathological relevance such as B. hominis and D. fragilis can be of diagnostic relevance due to their ability to promote or repress other pathogens. With the increasing availability of highly sensitive multiplexed molecular diagnostic approaches even in resource-limited settings, where multiple colonization of infection events with enteric pathogens in parallel are common, the importance of interpreting whole pathogen patterns rather than just individual pathogen detection may become more and more relevant.

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

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

Periprosthetic joint infection caused by kytococcus schroeteri: The first reported case and a review of the literature.

Oftentimes, Gram-positive cocci are the cause for periprosthetic joint infections (PJI). Most of these infections include bacteria such as Staphylococcus aureus, Staphylococcus epidermidis or other coagulase-negative staphylococci. We here present the first case of a PJI caused by Kytococcus schroeteri. While being a Gram-positive coccus, it is very rarely the cause for infections in the human body. K. schroeteri is part of the micrococcus branch and often encountered as a symbiotic bacterium living on the skin. Regarding its pathogenic potential, not a lot is known since less than a few dozen human infections have been reported worldwide. Furthermore, many of the cases reported are either associated with implanted material, especially heart valves, or associated with patients whose immune response is deficient. Only 3 reports of osteoarticular infections are described so far.

Microbiological Trends and Antibiotic Susceptibility Patterns in Patients with Periprosthetic Joint Infection of the Hip or Knee over 6 Years.

We sought to analyze trends of the causative pathogens and their antibiotic susceptibility patterns in patients with periprosthetic joint infections (PJI) of the hip and knee to get better insights and improve treatment. Retrospective evaluation of all consecutive patients with microbiological detection of a causative pathogen at a tertiary endoprothetic referral center between January 2016 and December 2021 in Germany was performed. Overall, 612 different microorganisms could be detected in 493 patients (hip: n = 293; knee: n = 200). Evaluation did not show a change in the relative abundance of pathogens detected, with coagulase-negative staphylococci (n = 275; 44.9%) found frequently, followed by S. aureus (n = 86; 14.1%), Enterococcus species (n = 57; 9.3%), Streptococcus species (n = 48; 7.8%), and Gram-negative bacteria (n = 80; 13.1%). Evaluation of the antibiotic susceptibilities showed increasing rates of oxacillin-resistant coagulase-negative staphylococci (60.4%; 46.8−76.7%) and piperacillin-tazobactam-resistant Gram-negative bacteria (26.5%; 0−57.1%), although statistically not significant. Resistance of Gram-positive bacteria to vancomycin (<1%) and Gram-negative microorganisms to meropenem (1.25%) remained an exception. In summary, coagulase-negative staphylococci, as the most frequent pathogen, displayed a continuously high rate of oxacillin resistance. For the highest antimicrobial coverage in the case of an empiric therapy/unknown pathogen, vancomycin might be chosen. Level of evidence: IV.

Microbiological Profiles of Patients with Periprosthetic Joint Infection of the Hip or Knee.

Periprosthetic joint infections (PJI) are one of the most devastating consequences after total joint arthroplasty. We sought to analyze the causative pathogens of patients with PJI to get better insights and improve treatment. We performed a retrospective study of all patients with PJI of the hip and knee with microbiological detection of a causative pathogen at a tertiary endoprothetic referral center between January 2016 and March 2021. A total of 432 cases with PJI (hip: n = 250; knee: n = 182) were included. The most common causative pathogen were coagulase-negative staphylococci (n = 240; 44.2%), of which Staphylococcus epidermidis (n = 144; 26.7%) was the most frequently detected, followed by S. aureus (n = 77; 14.3%) and enterococci (n = 49; 9%). Gram-negative pathogens and fungi could be detected in 21% (n = 136) and 2.4% (n = 13) of all cases. Overall, 60% of all coagulase-negative staphylococci were oxacillin-resistant, while none of these displayed to be vancomycin-resistant. In summary, the majority of pathogens in cases of PJI could be identified as coagulase-negative staphylococci. For empirical therapy vancomycin might provide the highest antimicrobial coverage in case of an unknown pathogen.

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

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

Comparison of Empiric Antibiotic Escalation Therapy with Vancomycin (VAN) versus Linezolid (LIN) in Patients with Febrile Neutropenia.

Background: In febrile neutropenia, either linezolid (LIN) or vancomycin (VAN) can be used if a gram-positive infection is suspected. Interestingly there is no literature in which both are compared in the setting of febrile neutropenia. Therefore, we provide here the results of a retrospective analysis of adding VAN versus LIN in patients with febrile neutropenia. Methods: Patients with haematological diseases and febrile neutropenia after myelosuppressive chemotherapy and no clearance of infection after the first empiric broad-spectrum antibiotic were escalated to VAN or LIN from 03/2010 to 03/2014 at the University Hospital Bonn were included in this retrospective analysis. Results: Out of the 73 patients, 50 had received VAN and 23 LIN. The median hospitalisation time in the LIN cohort was significantly shorter than in the VAN cohort (LIN 16 days vs VAN 20 days p=0.046). Successful defervescence with the escalation to VAN or LIN could be detected in 76% of the LIN cases and 50% in the VAN group (p=0.052). This trend to better efficacy with LIN was also shown by a higher rate of discontinuation of VAN and escalation to another antibiotic scheme (54.2%) than in the LIN cohort (24%, p=0.052). Conclusion: The antibiotic therapy in febrile neutropenia with LIN showed a trend of better efficacy than therapy with VAN. However, because of the small sample size and the retrospective manner, VAN may still be considered a reasonable option in neutropenic fever, and randomised studies are needed in this field.

Needs for an Integration of Specific Data Sources and Items - First Insights of a National Survey Within the German Center for Infection Research.

State-subsidized programs develop medical data integration centers in Germany. To get infection disease (ID) researchers involved in the process of data sharing, common interests and minimum data requirements were prioritized. In 06/2019 we have initiated the German Infectious Disease Data Exchange (iDEx) project. We have developed and performed an online survey to determine prioritization of requests for data integration and exchange in ID research. The survey was designed with three sub-surveys, including a ranking of 15 data categories and 184 specific data items and a query of available 51 data collecting systems. A total of 84 researchers from 17 fields of ID research participated in the survey (predominant research fields: gastrointestinal infections n=11, healthcare-associated and antibiotic-resistant infections n=10, hepatitis n=10). 48% (40/84) of participants had experience as medical doctor. The three top ranked data categories were microbiology and parasitology, experimental data, and medication (53%, 52%, and 47% of maximal points, respectively). The most relevant data items for these categories were bloodstream infections, availability of biomaterial, and medication (88%, 87%, and 94% of maximal points, respectively). The ranking of requests of data integration and exchange is diverse and depends on the chosen measure. However, there is need to promote discipline-related digitalization and data exchange.

The Performance of a Dithiothreitol-Based Diagnostic System in Diagnosing Periprosthetic Joint Infection Compared to Sonication Fluid Cultures and Tissue Biopsies.

PURPOSE: The aim of this study was to evaluate the performance of a commercially available dithiothreitol (DTT) kit for routine use in diagnosing periprosthetic joint infections (PJIs) in comparison to conventional microbiological tissue specimens and sonication procedures in a maximal care hospital. METHODS: We applied the DTT system in 40 consecutive cases of revision arthroplasty (23 PJIs and 17 aseptic revisions), with an exchange or a removal of components. The hardware components were split between the DTT system and the conventional sonication procedure. At least three tissue biopsies and a joint fluid specimen were sent for microbiological and histopathological analysis. Data was analysed retrospectively to compare between the different methods. RESULTS: Cultures of the DTT fluid showed a sensitivity of 65% and specificity of 100%, as referenced to conventional microbiological cultures. Sonication had better sensitivity (75%) but lower specificity (85%). The categorical agreement of DTT cultures compared to sonication fluid cultures was 78% (31/40). Neither pathogen type, infection duration nor antibiotic pretreatment influenced the accuracy of the DTT, but a low pH in the DTT seemed to be associated with false-negative results. CONCLUSION: DTT was inferior in sensitivity when diagnosing PJIs compared to sonication fluid cultures and tissue biopsies. A low pH in the DTT fluid correlated with false-negative results. Nevertheless, the closed system of the DTT kit avoids contamination and false-positive results, and DTT can be an alternative where sonication is not available.

Correction: ESBL Detection: Comparison of a Commercially Available Chromogenic Test for Third Generation Cephalosporine Resistance and Automated Susceptibility Testing in Enterobactericeae.

[This corrects the article DOI: 10.1371/journal.pone.0160203.].

Activity of ceftobiprole against Staphylococcus spec. isolates derived from foreign body associated infections.

Antibiotic therapy is essential in foreign body associated infections. The treatment regime should aim at high tissue concentrations, high bioavailability, high biofilm penetration and good tolerance. We investigated whether the new cephalosporin ceftobiprole is active against clinical isolates from musculoskeletal foreign body associated infections. One hundred ninety-six staphylococci isolates (coagulase negative staphylococci and Staphylococcus aureus) derived from foreign body associated infections were tested towards susceptibility to ceftobiprole, using a test strip assay and broth microdilution. The MIC for all strains S. aureus indicated susceptibility to ceftobiprole. The MIC of only two strains of coagulase negative staphylococci was above 2 mg/L. Our results show that ceftobiprole might be considered as an off-label treatment option in foreign body associated infections.

Novel Diagnostics in Revision Arthroplasty: Implant Sonication and Multiplex Polymerase Chain Reaction.

In orthopedic patients, foreign body-associated infections, especially periprosthetic joint infections (PJIs), are a devastating complication of arthroplasty. Infection requires complex treatment, may result in long hospitalization and causes considerable costs. Multiple surgical revisions can be necessary in these patients, with a loss in function as well as in quality of life. The routine preoperative diagnostics include blood examination for C-reactive protein (CRP) and other biomarkers, as well as joint aspirate analysis for cell count, differentiation, and culture. Intraoperative specimens for histology and microbiology are also standard procedure. The microbiological examination of removed implants with sonication, in combination with the implementation of molecular biology techniques in microbiology, represent two novel techniques currently employed to enhance the differential diagnostics of PJI. We present here the step-wise procedure of analyzing joint aspirate and sonication fluid, using a cartridge-based multiplex polymerase chain reaction (PCR) system. Results were matched against conventional cultures and consensus criteria for PJI. Conventional microbiological cultures from tissue biopsies, joint aspirate and sonication fluid showed a sensitivity of 66.7%, 66.7%, and 88.9%, respectively, and a specificity of 82.3%, 54.6%, and 61.5%, respectively. The PCR diagnostic of the sonication fluid and the joint fluid showed a sensitivity of 50.0% and 55.6%, respectively, and both a specificity of 100.0%. Both PCR diagnostics combined had a sensitivity of 66.7% and a specificity of 100.0%. The multiplex PCR therefore presents a rapid diagnostic tool with moderate sensitivity but high specificity in diagnosing PJI.

Successful Therapy of a Multidrug-Resistant Extended-Spectrum ß-Lactamase-Producing and Fluoroquinolone-Resistant Salmonella enterica Subspecies enterica Serovar Typhi Infection Using Combination Therapy of Meropenem and Fosfomycin.

We report a traveler who acquired a Salmonella enterica subspecies enterica serovar Typhi strain with resistance against ß-lactams, cephalosporins (extended-spectrum ß-lactamase-producing type SHV-12), and quinolones (plasmid-mediated quinolone resistance gene qnrB7). After clinical deterioration using meropenem monotherapy, treatment success was achieved after commencement of fosfomycin in conjunction with high-dose meropenem. The case illustrates clinical challenges of multidrug-resistant S. Typhi.

ESBL Detection: Comparison of a Commercially Available Chromogenic Test for Third Generation Cephalosporine Resistance and Automated Susceptibility Testing in Enterobactericeae.

Rapid detection and reporting of third generation cephalosporine resistance (3GC-R) and of extended spectrum betalactamases in Enterobacteriaceae (ESBL-E) is a diagnostic and therapeutic priority to avoid inefficacy of the initial antibiotic regimen. In this study we evaluated a commercially available chromogenic screen for 3GC-R as a predictive and/or confirmatory test for ESBL and AmpC activity in clinical and veterinary Enterobacteriaceae isolates. The test was highly reliable in the prediction of cefotaxime and cefpodoxime resistance, but there was no correlation with ceftazidime and piperacillin/tazobactam minimal inhibitory concentrations. All human and porcine ESBL-E tested were detected with exception of one genetically positive but phenotypically negative isolate. By contrast, AmpC detection rates lay below 30%. Notably, exclusion of piperacillin/tazobactam resistant, 3GC susceptible K1+ Klebsiella isolates increased the sensitivity and specificity of the test for ESBL detection. Our data further imply that in regions with low prevalence of AmpC and K1 positive E. coli strains chromogenic testing for 3GC-R can substitute for more time consuming ESBL confirmative testing in E. coli isolates tested positive by Phoenix or VITEK2 ESBL screen. We, therefore, suggest a diagnostic algorithm that distinguishes 3GC-R screening from primary culture and species-dependent confirmatory ESBL testing by ßLACTATM and discuss the implications of MIC distribution results on the choice of antibiotic regimen.