Frequency and clinical significance of Herpes simplex virus type 1/2 reactivation in adult patients with mild to moderately severe community-acquired pneumonia: a multicentre cohort study.

PURPOSE: This study assessed the frequency, clinical significance, and risk factors for Herpes simplex virus (HSV) reactivation in immunocompetent patients with community-acquired pneumonia (CAP). METHODS: The study included adult CAP-patients who were enrolled in the CAPNETZ study between 2007 and 2017 and had a residual sputum sample available for analysis. In addition to routine diagnostics, sputum and blood samples were tested for HSV-1/2 using PCR. Demographics, comorbidities, and CRB-65 score were compared between HSV-positive and negative patients using Fisher exact or Mann Whitney test. Logistic regression analyses investigated the influence of HSV reactivation on a modified hospital recovery scale (HRS) until day 7, divided into 3 categories (no oxygen therapy, oxygen therapy, ICU admission or death). RESULTS: Among 245 patients, HSV-1 and HSV-2 were detected in 30 patients (12.2%, 95%CI 8.7-16.9) and 0 patients, respectively. All HSV-positive patients were hospitalized, had a CRB-65 severity score of 0-2 and survived the first 28 day. In the HSV-positive group, patients had a non-significantly higher median age (70.5 versus 66 years) and a higher rate of oncological comorbidities (16.7% versus 8.8%) compared to the HSV-negative group. Distribution of co-pathogens and outcome parameters did not significantly differ between both groups. In a multivariate logistic regression model, age (AOR 1.029, p = 0.012) and CRB-65 score (AOR 1.709, p = 0.048), but not HSV-1 as single or co-pathogen were independently associated with higher HRS. CONCLUSION: Our study suggests that HSV-1 reactivation is common in CAP but might not be associated with specific risk factors or a complicated disease course.

Outcomes of complete removal versus conservative therapy in cardiac implantable electronic device infections - A systematic review and Meta-analysis.

BACKGROUND: Complete removal of cardiac implantable electronic devices (CIEDs) is recommended in patients with CIED infections, including both systemic and localized pocket infection. The aim of the study was to provide an up-to-date and comprehensive assessment of evidence relating to the effect of complete CIED extraction in patients with a CIED infection. METHODS: We performed a systematic review and meta-analysis of studies reporting short- and mid-term outcomes in patients who had a device infection or infective endocarditis (IE) and underwent complete removal of the cardiac device (generator and leads) compared to those who received conservative therapy (no removal, partial removal, local antibiotic infiltration or isolated antibiotic therapy). The primary outcome was reinfection/relapse. Secondary outcomes were short-term (30-day/in-hospital) and mid-term (mean follow-up: 43.0 months) mortality. Random effects model was performed. RESULTS: Thirty-two studies met the criteria for inclusion in the final analysis. Patients with complete CIED extraction (n = 905) exhibited a lower rate of relapse/re-infection compared to patients (n = 195) with a conservative treatment approach (n = 195, OR 0.02, 95%CI 0.01-0.06, p < 0.0001, mean-follow-up: 16.1 months). Additionally, these patients displayed a lower short- (OR 0.40, 95%CI 0.23-0.69, p = 0.01) and mid-term (OR 0.52, 95%CI 0.34-0.78, p = 0.002) mortality. CONCLUSIONS: The analysis indicates that patients with a CIED infection who undergo complete CIED extraction exhibit a lower rate of relapse/re-infection. Additionally, a lower short- and mid-term mortality is observed, although it is acknowledged that this outcome may be influenced by treatment allocation bias.

Long versus short course anti-microbial therapy of uncomplicated Staphylococcus aureus bacteraemia: a systematic review.

BACKGROUND: Current guidelines recommend at least 2 weeks duration of antibiotic therapy (DOT) for patients with uncomplicated Staphylococcus aureus bacteraemia (SAB) but the evidence for this recommendation is unclear. OBJECTIVES: To perform a systematic literature review assessing current evidence for recommended DOT for patients with SAB. METHODS: The following are the methods used for this study. DATA SOURCES: We searched MEDLINE, ISI Web of Science, the Cochrane Database and clinicaltrials.gov from inception to March 30, 2024. References of eligible studies were screened and experts in the field contacted for additional articles. STUDY ELIGIBILITY CRITERIA: All clinical studies, regardless of design, publication status and language. PARTICIPANTS: Adult patients with uncomplicated SAB. INTERVENTIONS: Long (>14 days; >18 days; 11-16 days) vs. short (≤14 days; 10-18 days; 6-10 days, respectively) DOT with the DOT being defined as the first until the last day of antibiotic therapy. ASSESSMENT OF RISK OF BIAS: Risk of bias was assessed using the ROBINS-I-tool. METHODS OF DATA SYNTHESIS: The primary outcome was 90-day all-cause mortality. Only studies presenting results of adjusted analyses for mortality were included. Data synthesis could not be performed. RESULTS: Eleven nonrandomized studies were identified that fulfilled the pre-defined inclusion criteria, of which three studies reported adjusted effect ratios. Only these were included in the final analysis. We did not find any RCT. Two studies with 1230 patients reported the primary endpoint 90-day all-cause mortality. Neither found a statistically significant superiority for longer (>14 days; 11-16 days) or shorter DOT (≤14 days; 6-10 days, respectively) for patients with uncomplicated SAB. Two studies investigated the secondary endpoint 30-day all-cause mortality (>18 days; 11-16 days vs. 10-18 days; 6-10 days, respectively) and did not find a statistically significant difference. All included studies had a moderate risk of bias. CONCLUSIONS: Sound evidence that supports any duration of antibiotic treatment for patients with uncomplicated SAB is lacking.

Teaching prudent antibiotic use on the go: a descriptive report on development, utilization and listener satisfaction of an educational podcast format for medical students and young professionals.

BACKGROUND: An important component in fostering the responsible use of antibiotics is training of new and future prescribers in this interdisciplinary topic. Because podcasts are playing an increasing role in medical education, we aimed to develop and evaluate a podcast format with practice and guideline-oriented learning content on antibiotic therapy for medical students and young medical professionals. METHODS: We developed the concept for the podcast with the direct involvement of medical students and medical experts with teaching experience. We used video conferencing when recording the episodes in order to have quick, easy, and nationwide access to the experts involved. We released an episode every 2 to 4 weeks on the popular podcast platforms. The podcast was promoted through mailing lists, social and print media, and at conferences. The evaluation of episodes was based on user data provided by the platforms and an anonymous feedback questionnaire linked to each episode in the podcast notes. RESULTS: Between December 2021 and December 2022 19 episodes of InfectEd: der Antibiotika-Podcast were released. The mean duration of an episode was 91 min. By March 9, 2023, a total of 38,829 downloads and streams had been recorded. The majority of users listened to the podcast on a mobile device. The average playing time per episode was 65%. The feedback questionnaire was completed 135 times. 60.7% of respondents were female, 38.5% male. The majority of respondents were in their twenties and thirties (66.7%). 31.1% were medical students, 25.9% were residents, and 25.2% were specialists. Listeners were asked to rate episodes on a scale from 1 to 6, where 1 was "very good" and 6 was "insufficient." Ratings did not differ significantly between female and male respondents or between medical students and others. 118 respondents (87.4%) reported an increase in knowledge. Free-text feedback frequently emphasized clinical and also exam relevance. CONCLUSION: Our podcast format, developed with a user-centered approach, was broadly distributed and has been well accepted by both medical students and physicians alike. It provides a large number of learners with low-threshold access to current, guideline-orientated content and could be a useful supplement to conventional teaching formats.

Effect of acyclovir therapy on the outcome of mechanically ventilated patients with lower respiratory tract infection and detection of herpes simplex virus in bronchoalveolar lavage: protocol for a multicentre, randomised controlled trial (HerpMV).

INTRODUCTION: Herpes simplex virus (HSV) is frequently detected in the respiratory tract of mechanically ventilated patients and is associated with a worse outcome. The aim of this study is to determine whether antiviral therapy in HSV-positive patients improves outcome. METHODS AND ANALYSIS: Prospective, multicentre, open-label, randomised, controlled trial in parallel-group design. Adult, mechanically ventilated patients with pneumonia and HSV type 1 detected in bronchoalveolar lavage (≥105 copies/mL) are eligible for participation and will be randomly allocated (1:1) to receive acyclovir (10 mg/kg body weight every 8 hours) for 10 days (or until discharge from the intensive care unit if earlier) or no intervention (control group). The primary outcome is mortality measured at day 30 after randomisation (primary endpoint) and will be analysed with Cox mixed-effects model. Secondary endpoints include ventilator-free and vasopressor-free days up to day 30. A total of 710 patients will be included in the trial. ETHICS AND DISSEMINATION: The trial was approved by the responsible ethics committee and by Germany's Federal Institute for Drugs and Medical Devices. The clinical trial application was submitted under the new Clinical Trials Regulation through CTIS (The Clinical Trials Information System). In this process, only one ethics committee, whose name is unknown to the applicant, and Germany's Federal Institute for Drugs and Medical Devices are involved throughout the entire approval process. Results will be published in a journal indexed in MEDLINE and CTIS. With publication, de-identified, individual participant data will be made available to researchers. TRIAL REGISTRATION NUMBER: NCT06134492.

Effect of haemoadsorption during cardiac surgery for Staphylococcus aureus endocarditis: a REMOVE trial post hoc analysis.

OBJECTIVES: Multi-organ failure is one of the leading causes of mortality after cardiac surgery for infective endocarditis (IE). Although the randomized evidence does not support the use of haemoadsorption during cardiac surgery for IE, observational studies suggest a beneficial effect in selected patient groups. Staphylococcus aureus is the most common pathogen, and its presence is an independent mortality predictor. We aimed to analyse the effect of haemoadsorption in patients with IE caused by S. aureus. METHODS: This is a post hoc analysis of the REMOVE trial that randomized 288 patients with IE who underwent cardiac surgery with haemoadsorption using CytoSorb® or control. The primary outcome was ΔSequential Organ Failure Assessment (SOFA), defined as the difference between the mean total postoperative and baseline SOFA score within 24 h of surgery. RESULTS: Among the total of 282 patients included in the modified intention-to-treat analysis of the REMOVE trial, 73 (25.9%) had S. aureus IE (38 patients in the haemoadsorption group and 35 patients in the control group). The overall ΔSOFA did not differ between the intervention groups in patients with S. aureus IE (mead difference = -0.4, 95% confidence interval -2.3 to 1.4, P = 0.66) and neither did 30-day mortality (hazard ratios = 1.32, 95% confidence interval 0.53-3.28, P = 0.55). No differences were observed with regard to any of the other secondary outcomes. CONCLUSIONS: Based on a post hoc analysis from REMOVE trial, the intraoperative use of haemoadsorption in patients with S. aureus IE was not associated with reduction of postoperative organ dysfunction, 30-day mortality or other major clinical end points.

Experience with PCR Testing for Enteric Bacteria and Viruses of Emergency Department Patients with Acute Gastroenteritis: Are There Implications for the Early Treatment of Clostridioides difficile Infection?

Early identification of acute gastroenteritis (AGE) pathogens via PCR may improve the management of patients presenting to the emergency department (ED). In this study, we evaluated the implementation of a testing algorithm for ED patients with AGE using the BD MAX automated PCR system. Data from 133 patients were analyzed. A total of 56 patients (42%) tested positive via PCR for at least one bacterial or viral pathogen. The median time to report PCR results was 6.17 h compared to 57.28 h for culture results for bacterial pathogens. The most common pathogen was Clostridioides difficile (n = 20, 15%). In total, 14 of the 20 C. difficile-positive patients were aged >65 years and 17 of the 20 patients (85%) were diagnosed with a clinically relevant infection based on typical symptoms and laboratory values. They received antibiotics, mostly oral vancomycin, starting a median of 11.37 h after ED admission. The introduction of PCR for the diagnosis of AGE infection in patients presenting to the ED may have the greatest impact on the rapid identification of C. difficile and the timely administration of antibiotics if necessary.

Conservative Versus Surgical Therapy in Patients With Infective Endocarditis and Surgical Indication-Meta-Analysis of Reconstructed Time-to-Event Data.

BACKGROUND: Infective endocarditis represents a life-threatening disease with high mortality rates. A fraction of patients receives exclusively conservative antibiotic treatment due to their comorbidities and high operative risk, despite fulfilling criteria for surgical therapy. The aim of the present study is to compare outcomes in patients with infective endocarditis and indication for surgical therapy in those who underwent or did not undergo valve surgery. METHODS AND RESULTS: Three databases were systematically assessed. A pooled analysis of Kaplan-Meier-derived reconstructed time-to-event data from studies with longer follow-up comparing conservative and surgical treatment was performed. A landmark analysis to further elucidate the effect of surgical intervention on mortality was carried out. Four studies with 3003 patients and median follow-up time of 7.6 months were included. Overall, patients with an indication for surgery who were surgically treated had a significantly lower risk of mortality compared with patients who received conservative treatment (hazard ratio [HR], 0.27 [95% CI, 0.24-0.31], P<0.001). The survival analysis in the first year showed superior survival for patients who underwent surgery when compared with those who did not at 1 month (87.6% versus 57.6%; HR, 0.31 [95% CI, 0.26-0.37], P<0.01), at 6 months (74.7% versus 34.6%) and at 12 months (73.3% versus 32.7%). CONCLUSIONS: Based on the findings of this study-level meta-analysis, patients with infective endocarditis and formal indication for surgical intervention who underwent surgery are associated with a lower risk of short- and long-term mortality when compared with conservative treatment.

Successful outpatient parenteral antibiotic therapy with cefiderocol for osteomyelitis caused by multi-drug resistant Gram-negative bacteria: a case report.

Objectives: Post-traumatic osteomyelitis attributed to metallo-ß-lactamase (MBL)-producing Gram-negative bacteria presents a challenging clinical scenario. Cefiderocol emerges as a viable treatment option within the limited therapeutic options available. Patient/case description: In this brief report, we present a case of a Ukrainian patient with osteomyelitis caused by multi-drug resistant Pseudomonas aeruginosa, which was successfully treated with cefiderocol, facilitated in part by outpatient parenteral antibiotic therapy (OPAT). Results and discussion: Administration of Cefiderocol via OPAT can present a safe and effective option for treatment of post-traumatic osteomyelitis with multi-drug resistant Pseudomonas aeruginosa. A possible effect on iron homeostasis of extended treatment duration with cefiderocol may be taken into consideration.

Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial.

BACKGROUND: Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection. METHODS: In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5-7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013-000577-77). FINDINGS: Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI -7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29). INTERPRETATION: Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy. FUNDING: Deutsche Forschungsgemeinschaft. TRANSLATIONS: For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section.

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 Controversial Effect of Antibiotics on Methicillin-Sensitive S. aureus: A Comparative In Vitro Study.

Methicillin-sensitive Staphylococcus (S.) aureus (MSSA) bacteremia remains a global challenge, despite the availability of antibiotics. Primary treatments include ß-lactam agents such as cefazolin and flucloxacillin. Ongoing discussions have focused on the potential synergistic effects of combining these agents with rifampicin or fosfomycin to combat infections associated with biofilm formation. Managing staphylococcal infections is challenging due to antibacterial resistance, biofilms, and S. aureus's ability to invade and replicate within host cells. Intracellular invasion shields the bacteria from antibacterial agents and the immune system, often leading to incomplete bacterial clearance and chronic infections. Additionally, S. aureus can assume a dormant phenotype, known as the small colony variant (SCV), further complicating eradication and promoting persistence. This study investigated the impact of antibiotic combinations on the persistence of S. aureus 6850 and its stable small colony variant (SCV strain JB1) focusing on intracellular survival and biofilm formation. The results from the wild-type strain 6850 demonstrate that ß-lactams combined with RIF effectively eliminated biofilms and intracellular bacteria but tend to select for SCVs in planktonic culture and host cells. Higher antibiotic concentrations were associated with an increase in the zeta potential of S. aureus, suggesting reduced membrane permeability to antimicrobials. When using the stable SCV mutant strain JB1, antibiotic combinations with rifampicin successfully cleared planktonic bacteria and biofilms but failed to eradicate intracellular bacteria. Given these findings, it is reasonable to report that ß-lactams combined with rifampicin represent the optimal treatment for MSSA bacteremia. However, caution is warranted when employing this treatment over an extended period, as it may elevate the risk of selecting for small colony variants (SCVs) and, consequently, promoting bacterial persistence.

Software- and TDM-Guided Dosing of Meropenem Promises High Rates of Target Attainment in Critically Ill Patients.

Various studies have reported insufficient beta-lactam concentrations in critically ill patients. The optimal dosing strategy for beta-lactams in critically ill patients, particularly in septic patients, is an ongoing matter of discussion. This retrospective study aimed to evaluate the success of software-guided empiric meropenem dosing (CADDy, Calculator to Approximate Drug-Dosing in Dialysis) with subsequent routine meropenem measurements and expert clinical pharmacological interpretations. Adequate therapeutic drug exposure was defined as concentrations of 8-16 mg/L, whereas concentrations of 16-24 mg/L were defined as moderately high and concentrations >24 mg/L as potentially harmful. A total of 91 patients received meropenem as a continuous infusion (229 serum concentrations), of whom 60% achieved 8-16 mg/L, 23% achieved 16-24 mg/L, and 10% achieved unnecessarily high and potentially harmful meropenem concentrations >24 mg/L in the first 48 h using the dosing software. No patient showed concentrations <2 mg/L using the dosing software in the first 48 h. With a subsequent TDM-guided dose adjustment, therapeutic drug exposure was significantly (p ≤ 0.05) enhanced to 70%. No patient had meropenem concentrations >24 mg/L with TDM-guided dose adjustments. The combined use of dosing software and consecutive TDM promised a high rate of adequate therapeutic drug exposures of meropenem in patients with sepsis and septic shock.

Towards model-informed precision dosing of piperacillin: multicenter systematic external evaluation of pharmacokinetic models in critically ill adults with a focus on Bayesian forecasting.

PURPOSE: Inadequate piperacillin (PIP) exposure in intensive care unit (ICU) patients threatens therapeutic success. Model-informed precision dosing (MIPD) might be promising to individualize dosing; however, the transferability of published models to external populations is uncertain. This study aimed to externally evaluate the available PIP population pharmacokinetic (PopPK) models. METHODS: A multicenter dataset of 561 ICU patients (11 centers/3654 concentrations) was used for the evaluation of 24 identified models. Model performance was investigated for a priori (A) predictions, i.e., considering dosing records and patient characteristics only, and for Bayesian forecasting, i.e., additionally including the first (B1) or first and second (B2) therapeutic drug monitoring (TDM) samples per patient. Median relative prediction error (MPE) [%] and median absolute relative prediction error (MAPE) [%] were calculated to quantify accuracy and precision. RESULTS: The evaluation revealed a large inter-model variability (A: MPE - 135.6-78.3% and MAPE 35.7-135.6%). Integration of TDM data improved all model predictions (B1/B2 relative improvement vs. A: |MPE|median_all_models 45.1/67.5%; MAPEmedian_all_models 29/39%). The model by Kim et al. was identified to be most appropriate for the total dataset (A/B1/B2: MPE - 9.8/- 5.9/- 0.9%; MAPE 37/27.3/23.7%), Udy et al. performed best in patients receiving intermittent infusion, and Klastrup et al. best predicted patients receiving continuous infusion. Additional evaluations stratified by sex and renal replacement therapy revealed further promising models. CONCLUSION: The predictive performance of published PIP models in ICU patients varied considerably, highlighting the relevance of appropriate model selection for MIPD. Our differentiated external evaluation identified specific models suitable for clinical use, especially in combination with TDM.

Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. Objective: To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. Evidence Review: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. Findings: A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. Conclusions and Relevance: In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed.

Early treatment response to piperacillin/tazobactam in patients with bloodstream infections caused by non-ESBL ampicillin/sulbactam-resistant Escherichia coli: a binational cohort study.

PURPOSE: This study aimed to compare treatment outcomes for bloodstream infections (BSI) caused by a piperacillin/tazobactam (PIP/TAZ)-susceptible E. coli among three patient groups: BSI caused by ampicillin/sulbactam (AMP/SLB)-resistant isolates treated with PIP/TAZ, BSI caused by AMP/SLB-sensitive isolates treated with PIP/TAZ, and BSI caused by AMP/SLB-resistant isolates treated with another monotherapy. METHODS: This retrospective study was conducted in two academic centres in Europe. Adult patients with E. coli BSI were screened from 2014 to 2020. Inclusion criteria were non-ESBL BSI and initial monotherapy for ≥ 72 h. To reduce the expected bias between the patient groups, propensity score matching was performed. The primary outcome was early treatment response after 72 h and required absence of SOFA score increase in ICU/IMC patients, as well as resolution of fever, leukocytosis, and bacteraemia. RESULTS: Of the 1707 patients screened, 315 (18.5%) were included in the final analysis. Urinary tract infection was the most common source of BSI (54.9%). Monotherapies other than PIP/TAZ were cephalosporins (48.6%), carbapenems (34.3%), and quinolones (17.1%). Enhanced early treatment response rate was detected (p = 0.04) in patients with BSI caused by AMP/SLB-resistant isolates treated with another monotherapy (74.3%) compared to those treated with PIP/TAZ (57.1%), and was mainly driven by the use of cephalosporins and quinolones (p ≤ 0.03). Clinical success, 28-day mortality, and rate of relapsing BSI did not significantly differ between the groups. CONCLUSIONS: Our study suggests that initial use of PIP/TAZ may be associated with reduced early treatment response in E. coli BSI caused by AMP/SLB-resistant isolates compared to alternative monotherapies.

Towards therapeutic drug monitoring of antibiotic levels - analyzing the pharmacokinetics of levofloxacin using DUV-resonance Raman spectroscopy.

Therapeutic drug monitoring (TDM) plays an important role in clinical practice. Here, pharmacokinetics has a decisive influence on the effective antibiotic concentration during treatment. Moreover, different kinetics exist for different administration forms. Accordingly, adjusting the correct concentration depends, in addition to gender, age, weight, clinical picture, etc., on the dosage form of the antibiotic. This study investigates the capability of deep UV resonance Raman spectroscopy (DUV-RRS) to simulate the pharmacokinetics of fluoroquinolone levofloxacin after two different administration forms (intravenous and oral). Three different pre-processing methods were applied, and the best agreement with the simulation was achieved using the extended multiplicative scatter correction. The resulting spectra were used for partial least squares (PLS) regression and ordinary least squares (OLS) regression. The kinetic parameters were compared with the simulated data, with PLS showing the best performance for intravenous administration and a comparable result to OLS for oral administration, while the errors are smaller. The acquired results show the potential of DUV-RRS in combination with PLS regression as a promising supportive method for TDM.

Streptococcus pneumoniae re-emerges as a cause of community-acquired pneumonia, including frequent co-infection with SARS-CoV-2, in Germany, 2021.

In Germany, the proportion of community-acquired pneumonia due to Streptococcus pneumoniae rebounded to a near-pandemic level in the second half of 2021. Vaccination uptake against respiratory pathogens, including S. pneumoniae, should be strengthened. https://bit.ly/3JMlwFt.

Respiratory Infections in the Aging Lung: Implications for Diagnosis, Therapy, and Prevention.

Respiratory infections pose a significant health problem among elderly individuals, particularly during the COVID-19 pandemic. The increased mortality and morbidity rates among individuals over 65 highlight the criticality of these infections. The normal aging process in the lungs increases vulnerability to respiratory infections due to the accumulation of cellular damage and senescence. Consequently, the lung environment undergoes major changes in mechanical function and other systemic factors. This review aims to examine the influence of aging on respiratory infections from a clinical perspective by analyzing clinical studies. Additionally, the review will emphasize potential prevention and diagnostic developments to enhance therapy options available for elderly patients over 65 years of age.

[Therapy-relevant antibiotic resistances in a One Health context]. / Therapierelevante Antibiotikaresistenzen im One-Health-Kontext.

One Health refers to a concept that links human, animal, and environmental health. In Germany, there is extensive data on antibiotic resistance (AMR) and multidrug-resistant (micro)organisms (MDRO) in human and veterinary medicine, as well as from studies in various environmental compartments (soil, water, wastewater). All these activities are conducted according to different specifications and standards, which makes it difficult to compare data. A focus on AMR and MDRO of human therapeutic importance is helpful to provide some guidance. Most data are available across sectors on methicillin-resistant Staphylococcus aureus (MRSA) and multiresistant Enterobacterales such as Escherichia coli and Klebsiella pneumoniae. Here, the trends of resistance are heterogeneous. Antibiotic use leads to MRE selection, which is well documented. Success in minimizing antibiotic use has also been demonstrated in recent years in several sectors and could be correlated with success in containing AMR and MDRO (e.g., decrease in MRSA in human medicine). Sector-specific measures to reduce the burden of MDRO and AMR are also necessary, as not all resistance problems are linked to other sectors. Carbapenem resistance is still rare, but most apparent in human pathogens. Colistin resistance occurs in different sectors but shows different mechanisms in each. Resistance to antibiotics of last resort such as linezolid is rare in Germany, but shows a specific One Health correlation. Efforts to harmonize methods, for example in the field of antimicrobial susceptibility testing and genome-based pathogen and AMR surveillance, are an important first step towards a better comparability of the different data collections.