Outcome and microbiological findings of patients with cardiac implantable electronic device infection.

INTRODUCTION: Infections associated with cardiac implantable electronic devices (CIEDs) are a multifactorial disease that leads to increased morbidity and mortality. OBJECTIVE: The aim was to analyze patient-, disease- and treatment-related characteristics including microbiological and bacterial spectrum according to survival status and to identify risk factors for 1- and 3-year mortality in patients with local and systemic CIED infection. METHODS: In a retrospective cohort study, we analyzed data from patients with CIED-related local or systemic infection undergoing successful transvenous lead extraction (TLE). Survival status as well as incidence and cause of rehospitalization were recorded. Microbiology and antibiotics used as first-line therapy were compared according to mortality. Independent risk factors for 1- and 3-year mortality were determined. RESULTS: Data from 243 Patients were analyzed. In-hospital mortality was 2.5%. Mortality rates at 30 days, 1- and 3 years were 4.1%, 18.1% and 30%, respectively. Seventy-four (30.5%) patients had systemic bacterial infection. Independent risk factors for 1-year mortality included age (OR 1.05 [1.01-1.10], p = 0.014), NT-proBNP at admission (OR 4.18 [1.81-9.65], p = 0.001), new onset or worsened tricuspid regurgitation after TLE (OR 6.04 [1.58-23.02], p = 0.009), and systemic infection (OR 2.76 [1.08-7.03], p = 0.034), whereas systemic infection was no longer an independent risk factor for 3-year mortality. Staphylococcus aureus was found in 18.1% of patients who survived and in 25% of those who died, p = 0.092. There was a high proportion of methicillin-resistant strains among coagulase-negative staphylococci (16.5%) compared to Staphylococcus aureus (1.2%). CONCLUSIONS: Staphylococci are the most common causative germs of CIED-infection with coagulase-negative staphylococci showing higher resistance rates to antibiotics. The independent risk factors for increased long-term mortality could contribute to individual risk stratification and well-founded treatment decisions in clinical routine. Especially the role of tricuspid regurgitation as a complication after TLE should be investigated in future studies.

Effect of a multimodal prevention strategy on dialysis-associated infection events in outpatients receiving haemodialysis: The DIPS stepped wedge, cluster-randomized trial.

OBJECTIVES: Patients with haemodialysis catheters are susceptible to dialysis-associated infections, particularly bloodstream infections. There have been few systematic attempts to reduce this burden. Our study aimed to investigate the effect of a multimodal prevention strategy on dialysis-associated infection events (DAIE) among haemodialysis outpatients. METHODS: A multicentre, stepped wedge, cluster-randomized controlled trial was done from October 2019 to September 2021. Outpatient dialysis facilities entered into the intervention phase in three randomly assigned clusters, at three predefined time points. The multimodal prevention strategy consisted of infection surveillance and hand hygiene (HH) compliance observation with active feedback and teaching aseptic procedures, and a patient flyer. The primary outcome was incidence rates of different DAIE, such as bloodstream infections, intravenous antimicrobial starts, and local access-site infections per 1000 dialysis. As secondary outcome, we analysed the HH compliance change. RESULTS: A total of 43 haemodialysis outpatient facilities with 11 251 patients and 1 413 457 proceeded haemodialysis were included in the DIPS-trial. Incidence rates were 0.71 DAIE per 1000 dialysis (95% CI, 0.65-0.78) in the control and 0.31 (95% CI, 0.27-0.36) in the intervention group. The univariable analysis yielded an incidence rate ratio (IRR) of 0.44 (95% CI, 0.33-0.59) for DAIE. Especially in patients with a central venous catheter, we saw a significant decrease in DAIE in the intervention group (IRR 0.4; 95% CI, 0.28-0.58). The HH observation combined with feedback and intensified training, resulted in an increase of HH compliance from 58-65%. DISCUSSION: A multimodal prevention strategy showed a significant preventive effect on DAIE among haemodialysis outpatients. This reduction also applied to bloodstream infections, especially in patients with a central venous catheter.

High frequency of Enterococcus faecalis detected in urinary tract infections in male outpatients - a retrospective, multicenter analysis, Germany 2015 to 2020.

BACKGROUND: Urinary tract infections (UTI) in men differ relevantly to women by their pathogens. Gram-positive uropathogens play a relevant role in UTI in men. In this study, we aimed to analyze the epidemiology of Enterococcus faecalis in UTI in male outpatients. METHODS: We conducted a retrospective observational multicenter study during 2015 to 2020 consisting of urine samples of 99,415 adult male outpatients sent from 6,749 outpatient practices from Germany. Proportions were compared using the z-Test and 95% confidence intervals were calculated using the Clopper-Pearson method. RESULTS: E. faecalis is the 2nd most frequent bacteria (16%) detected in suspected UTI in male outpatients. Young men are predominantly at risk (17%) for isolation of E. faecalis in suspected UTI. In polymicrobial infections E. faecalis is isolated in 47% of all suspected UTI in men. Recurrency of suspected UTI is significantly more frequent when E. faecalis is isolated compared to Escherichia coli (22% vs 26%; p < .001). Recurrency rates of E. faecalis associated UTI increases by age from 12% (18-29 years) to 28% ([Formula: see text] 70 years); p < .001. Congruently the resistance of E. faecalis against ciprofloxacin increases by age from 22% (18-29 years; 2019) to 37% ([Formula: see text] 70 years; 2019); p < .001. CONCLUSIONS: E. faecalis is frequently isolated in suspected UTI in male patients. Consequently, Nitrate-sticks results cannot be recommended to exclude UTI in men. The empirical use of ciprofloxacin in young adults can be reasonable. Frequent recurrences in E. faecalis associated suspected UTI emphasizes the importance of microbiological pathogen identification and susceptibility testing in men suffering from UTI.

Should We Use Rifampicin in Periprosthetic Joint Infections Caused by Staphylococci When the Implant Has Been Exchanged? A Multicenter Observational Cohort Study.

Background: Previous studies demonstrated the efficacy of a rifampicin-based regimen in the treatment of acute staphylococcal periprosthetic joint infections (PJIs) treated with surgical debridement. However, evidence is lacking to support the use of rifampicin in cases where the implant is exchanged during revision. Methods: We included all consecutive cases of staphylococcal PJIs treated from January 2013 to December 2018 with revision surgery in this international, retrospective, multicenter observational cohort study. PJI was defined according to the European Bone and Joint Infection Society diagnostic criteria. A relapse or reinfection during follow-up, the need for antibiotic suppressive therapy, the need for implant removal, and PJI-related death were defined as clinical failure. Cases without reimplantation or with follow-up <12 months were excluded. Results: A total of 375 cases were included in the final analysis, including 124 1-stage exchanges (33.1%) and 251 2-stage exchanges (66.9%). Of those, 101 cases failed (26.9%). There was no statistically significant difference in failure of patients receiving rifampicin (22.5%, 42/187) and those not receiving rifampicin (31.4%, 59/188; P = .051). A subanalysis of chronic PJIs treated by 2-stage exchange arthroplasty demonstrated a lower failure rate in cases treated with rifampicin (15%) compared with the no-rifampicin group (35.5%; P = .005). In this subgroup, the use of rifampicin and an antibiotic holiday of >2 weeks were independent predictors of clinical success (odds ratio [OR], 0.36; 95% CI, 0.15-0.88; and OR, 0.19; 95% CI, 0.04-0.90; respectively). Conclusions: Combination treatment with rifampicin increases treatment success in patients with chronic staphylococcal PJI treated with 2-stage exchange arthroplasty.

Arterial leg ulcers-Bacterial patterns, antimicrobial resistance and clinical characteristics, a retrospective single-centre cohort, 2012-2021.

OBJECTIVE: Severe wound infections in patients with peripheral artery disease (PAD) are common, potentially life- and limb-threatening, and difficult to treat. Evidence on patients with infected leg ulcers in PAD is scarce. This study aims to provide insight into the microbiological patterns and antimicrobial resistance (AMR) of specific pathogens in patients with arterial leg ulcers. METHODS AND DESIGN: In this retrospective, consecutive, single-centre study 16,553 patients underwent an endovascular revascularization procedure between 2012 and 2021. Of these, 1,142 patients had PAD Rutherford category 5 or 6 with infected leg ulcers. Logistic regression was used to identify risk factors for Staphylococcus aureus-associated infections. RESULTS: A total of 3,431 bacterial isolates were detected, of which 2,335 (68.1%) bacterial isolates were gram-positive and 1,096 (31.9%) were gram-negative species. The most prevalent bacteria were S. aureus (18.6%), Enterococcus faecalis (9.1%) and S. epidermidis (7.8%). Pseudomonas aeruginosa (5.6%), Proteus mirabilis (3.7%) and Escherichia coli (3.4%). The resistance of S. aureus isolates to clindamycin was 11.0%. Resistance to oxacillin was rare (1.5%). P. aeruginosa is frequently resistant to ciprofloxacin (14.4%) whilst intrinsically resistant to trimethoprim/sulfamethoxazole. P. mirabilis and E. coli were frequently resistant to both ciprofloxacin (7.3; 20.7%) and trimethoprim/sulfamethoxazole (24.6; 22.6%), respectively. Resistance to amoxicillin/clavulanic acid was high among E. coli isolates (36.8%). Multi-drug resistance (MDR) was rare among S. aureus and P. aeruginosa isolates. In contrast, the proportion of MDR was high in E. coli isolates. End-stage renal disease was independently positively associated with S. aureus identification (p = .042). CONCLUSION: S. aureus was the most common pathogen in arterial leg ulcers with end-stage renal disease being an independent risk factor. Clindamycin resistance was common, making empirical therapy likely to fail. Isolated E. coli species had a high proportion of MDR.

Stability and C-H Bond Activation Reactions of Palladium(I) and Platinum(I) Metalloradicals: Carbon-to-Metal H-Atom Transfer and an Organometallic Radical Rebound Mechanism.

One-electron oxidation of palladium(0) and platinum(0) bis(phosphine) complexes enables isolation of a homologous series of linear d9 metalloradicals of the form [M(PR3)2]+ (M = Pd, Pt; R = tBu, Ad), which are stable in 1,2-difluorobenzene (DFB) solution for >1 day at room temperature when partnered with the weakly coordinating [BArF4]- (ArF = 3,5-(CF3)2C6H3) counterion. The metalloradicals exhibit reduced stability in THF, decreasing in the order palladium(I) > platinum(I) and PAd3 > PtBu3, especially in the case of [Pt(PtBu3)2]+, which is converted into a 1:1 mixture of the platinum(II) complexes [Pt(PtBu2CMe2CH2)(PtBu3)]+ and [Pt(PtBu3)2H]+ upon dissolution at room temperature. Cyclometalation of [Pt(PtBu3)2]+ can also be induced by reaction with the 2,4,6-tri-tert-butylphenoxyl radical in DFB, and a common radical rebound mechanism involving carbon-to-metal H-atom transfer and formation of an intermediate platinum(III) hydride complex, [Pt(PtBu2CMe2CH2)H(PtBu3)]+, has been substantiated by computational analysis. Radical C-H bond oxidative addition is correlated with the resulting MII-H bond dissociation energy (M = Pt > Pd), and reactions of the metalloradicals with 9,10-dihydroanthracene in DFB at room temperature provide experimental evidence for the proposed C-H bond activation manifold in the case of platinum, although conversion into platinum(II) hydride derivatives is considerably faster for [Pt(PtBu3)2]+ (t1/2 = 1.2 h) than [Pt(PAd3)2]+ (t1/2 ∼ 40 days).

PCP Pincer Complexes of Titanium in the +3 and +4 Oxidation States.

Ti(IV) and Ti(III) complexes using the tBuPCP ligand have been synthesized (tBuPCP = C6H3-2,6-(CH2PtBu2)2). The [tBuPCP]Li synthon can be reacted with TiCl4(THF)2 to form (tBuPCP)TiCl3 (1) in limited yields due to significant reduction of the titanium synthon. The Ti(III) complex (tBuPCP)TiCl2 (2) has been further characterized. This can have half an equivalent of halide abstracted to form [{(tBuPCP)TiCl}2{µ-Cl}][B(C6F5)4] (3) and can also be methylated, forming (tBuPCP)TiMe2 (4). All the Ti(III) complexes have been characterized using EPR and X-ray crystallography, giving insight into their electronic structures, which are further supported by DFT calculations.

AT 1 inhibition mediated neuroprotection after experimental traumatic brain injury is dependent on neutrophils in male mice.

After traumatic brain injury (TBI) cerebral inflammation with invasion of neutrophils and lymphocytes is a crucial factor in the process of secondary brain damage. In TBI the intrinsic renin-angiotensin system is an important mediator of cerebral inflammation, as inhibition of the angiotensin II receptor type 1 (AT1) reduces secondary brain damage and the invasion of neutrophil granulocytes into injured cerebral tissue. The current study explored the involvement of immune cells in neuroprotection mediated by AT1 inhibition following experimental TBI. Four different cohorts of male mice were examined, investigating the effects of neutropenia (anti-Ly6G antibody mediated neutrophil depletion; C57BL/6), lymphopenia (RAG1 deficiency, RAG1-/-), and their combination with candesartan-mediated AT1 inhibition. The present results showed that reduction of neutrophils and lymphocytes, as well as AT1 inhibition in wild type and RAG1-/- mice, reduced brain damage and neuroinflammation after TBI. However, in neutropenic mice, candesartan did not have an effect. Interestingly, AT1 inhibition was found to be neuroprotective in RAG1-/- mice but not in neutropenic mice. The findings suggest that AT1 inhibition may exert neuroprotection by reducing the inflammation caused by neutrophils, ultimately leading to a decrease in their invasion into cerebral tissue.

Screening for Methicillin-Resistant Staphylococcus aureus.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has become less common in Germany in recent years. In this paper, we report data from the MRSA module of the Hospital Infection Surveillance System (Krankenhaus-Infektionen- Surveillance-System, KISS) for the years 2006-2021. We also describe the association of MRSA rates with the frequency of patient screening for MRSA and discuss the findings. METHODS: Participation in the MRSA KISS module is voluntary. Once a year, the participating hospitals submit structural data, information on cases in which MRSA was detected (both colonizations and infections; both detected on admission and nosocomially acquired), and the number of nasal swabs taken for the detection of MRSA to the German National Reference Center for the Surveillance of Nosocomial Infections. Statistical analyses were performed with R software. RESULTS: The number of hospitals participating in the MRSA module rose from 110 in 2006 to 525 in 2021. From 2006 onward, the overall MRSA prevalence in German hospitals increased, reaching a maximum of 1.04 cases per 100 patients in 2012. The prevalence on admission fell by 44% from 0.96 in 2016 to 0.54 in 2021. The incidence density of nosocomial MRSA fell by an average of 12% per year, from 0.27 per 1000 patient-days in 2006 to 0.06 in 2021, while MRSA screening frequency increased sevenfold by 2021. The nosocomial incidence density was stable, independently of the screening frequency. CONCLUSION: MRSA rates in German hospitals fell markedly from 2006 to 2021, reflecting a general trend. The incidence density was no higher in hospitals with a low or moderate screening frequency than in those with a high one. Thus, a targeted, riskadapted MRSA screening strategy on hospital admission can be recommended.

Age as a risk factor for surgical site infections: German surveillance data on total hip replacement and total knee replacement procedures 2009 to 2018.

BackgroundOlder age is frequently cited as a risk factor for healthcare-associated infections in general, and surgical site infections (SSIs) specifically.AimWe aimed to investigate the correlation between age and SSI occurrence.MethodsData on total hip replacement (THR) and total knee replacement (TKR) surgeries and resulting SSIs documented in the German national surveillance network from a 10-year period from 2009 to 2018 were selected for analysis. SSI rates and adjusted odds ratios (AOR) were calculated and a multivariable analysis to determine risk factors for SSI occurrence was conducted.ResultsA total of 418,312 THR procedures resulting in 3,231 SSIs, and 286,074 TKR procedures with 1,288 SSIs were included in the analyses. For THR, SSI rates were higher in older age groups when compared with the reference age group of 61-65 years. A significantly higher risk was observed in the 76-80 years age group (AOR: 1.21, 95% CI: 1.05-1.4). An age of ≤ 50 years was associated with a significantly lower SSI risk (AOR: 0.64, 95% CI: 0.52-0.8). For TKR, a similar correlation was observed, with the exception of the youngest age group (≤ 52 years), which was shown to have an SSI risk equal to that of the knee prosthesis reference age group (78-82 years).ConclusionA strong correlation between increasing age and SSI occurrence was observed for both procedure types. The results of our analyses provide a basis to consider future targeted SSI prevention measures for different age groups.

Cationic Triarylchlorostibonium Lewis Acids.

Organopnictogen cations show promise as powerful, tunable main-group Lewis acid catalysts. The synthesis, solid-state structures, and reactivity of a series of weakly coordinated triarylchlorostibonium salts [Ar3SbCl][B(C6F5)4] (Ar = Ph, 3-FC6H4, 4-FC6H4, 3,5-F2C6H3, 2,4,6-F3C6H2) are reported. The cation in each adopts a tetrahedral coordination environment of antimony, with near complete separation from the anion. Structural, computational, and reactivity studies reveal that the Lewis acidity of [Ar3SbCl]+ generally increases with increased fluorination of the Ar substituents, with a secondary quenching effect from para fluorination. [Ar3SbCl]+ is reduced to Ar3Sb in the presence of Et3SiH, and the mechanism of this reaction has been modeled computationally. Preliminary studies demonstrate that they are useful catalysts for the dimerization of 1,1-diphenylethylene and the Friedel-Crafts alkylation of benzene.

Early DNase-I therapy delays secondary brain damage after traumatic brain injury in adult mice.

Traumatic brain injury (TBI) causes the release of danger-associated molecular patterns (DAMP) from damaged or dead cells, which contribute to secondary brain damage after TBI. Cell-free DNA (cfDNA) is a DAMP known to cause disruption of the blood-brain barrier (BBB), promote procoagulant processes, brain edema, and neuroinflammation. This study tested the hypothesis that administration of deoxyribonuclease-I (DNase-I) has a beneficial effect after TBI. Mice (n = 84) were subjected to controlled cortical impact (CCI) and posttraumatic intraperitoneal injections of low dose (LD) or high dose (HD) of DNase-I or vehicle solution at 30 min and 12 h after CCI. LD was most effective to reduce lesion volume (p = 0.003), brain water content (p < 0.0001) and to stabilize BBB integrity (p = 0.019) 1 day post-injury (dpi). At 6 h post injury LD-treated animals showed less cleavage of fibrin (p = 0.0014), and enhanced perfusion as assessed by micro-computer-tomography (p = 0.027). At 5 dpi the number of Iba1-positive cells (p = 0.037) were reduced, but the number of CD45-positive cells, motoric function and brain lesion volume was not different. Posttraumatic-treatment with DNase-I therefore stabilizes the BBB, reduces the formation of brain edema, immune response, and delays secondary brain damage. DNase-I might be a new approach to extend the treatment window after TBI.

Chlorhexidine and octenidine susceptibility of bacterial isolates from clinical samples in a three-armed cluster randomised decolonisation trial.

BACKGROUND: Routine use of chlorhexidine or octenidine for antiseptic bathing may have unintended consequences. Our analysis aimed to assess the phenotypic susceptibility of bacterial isolates from clinical samples to chlorhexidine and octenidine collected from intensive care units (ICU) that routinely used 2% chlorhexidine-impregnated wash cloths or 0.08% octenidine wash mitts (intervention) or water and soap (control) for daily patient care. METHODS: This study was conducted within the context of a three armed cluster-randomised controlled decolonisation trial (Registration number DRKS00010475, registration date August 18, 2016). Bacterial isolates were collected prior to and at the end of a 12-month-intervention period from patients with ≥ 3 days length of stay at an ICU assigned to one of two intervention groups or the control group. Phenotypic susceptibility to chlorhexidine and octenidine was assessed by an accredited contract research laboratory determining minimal inhibitory concentrations (MIC) as percentage of extraction solutions used. MIC were reported as estimated concentrations in µg/ml derived from the chlorhexidine and octenidine extraction solutions. Statistical analyses including generalized estimating equation models were applied. RESULTS: In total, 790 ICU-attributable bacterial isolates from clinical samples (e.g. blood, urine, tracheal aspirate) were eligible for all analyses. Pathogens included were Staphylococcus aureus (n = 155), coagulase-negative staphylococci (CoNS, n = 122), Escherichia coli (n = 227), Klebsiella spp. (n = 150) and Pseudomonas aeruginosa (n = 136). For all species, chlorhexidine and octenidine MIC did not increase from baseline to intervention period in the antiseptic bathing groups. For proportions of bacterial isolates with elevated chlorhexidine / octenidine MIC (≥ species-specific chlorhexidine / octenidine MIC50), adjusted incidence rate ratios (aIRR) showed no differences between the intervention groups and the control group (intervention period). CONCLUSION: We found no evidence for reduced phenotypic susceptibilities of bacterial isolates from clinical samples to chlorhexidine or octenidine in ICUs 12 months after implementation of routine antiseptic bathing with the respective substances.

Gauging the donor strength of iron(0) complexes via their N-heterocyclic carbene gold(I) adducts.

We isolate and characterize the gold(I)-iron(0) adducts [(iPr2-bimy)Au-Fe(CO)3(PMe3)2][BArF4] and [Au-{Fe(CO)3(PMe3)2}2][BArF4] (iPr2-bimy = 1,3-diisopropylbenzimidazolin-2-ylidene, BArF4 = tetrakis(pentafluorophenyl)borate). DFT analysis reveals that the gold-iron interaction in [(iPr2-bimy)Au-Fe(CO)3(PMe3)2][BArF4] is predominantly a σ-donation from iron to gold. We further extend this class of compounds to include [(iPr2-bimy)Au-Fe(CO)3(PR3)2][BArF4] (PR3 = PPh3, PCy3, PCyPh2, PMePh2, PMe2Ph, P(4-C6H4F)3) and [(iPr2-bimy)Au-Fe(CO)4(PPh3)][BArF4] and correlate the iPr2-bimy carbenic 13C NMR signal with the relative donor strength of the iron(0) ligand. This approach allows for a fast and simple approach to gauge relative donor strength of Fe(0) donors.

Synthesis and reactivity of titanium 'POCOP' pincer complexes.

The 'POCOP' pincer ligand, [2,6-(OPR2)2C6H3], has been attached to titanium in both Ti(III) and Ti(IV) complexes for the first time. Using a lithium-halogen exchange route [2,6-(OPR2)2C6H3]Li ([RPOCOP]Li) can be synthesised. Both the iso-propyl and tert-butyl derivatives can be made, but only the latter isolated. These can be reacted with the Ti(III) and Ti(IV) synthons to make a range of [POCOP]TiClx species. In the presence of Ti(IV), THF and [RPOCOP]Li, an unprecedented ligand rearrangement occurs. (tBuPOCOP)TiCl2, 1, can be derivatised with alkylating agents to make bis-methyl, phenyl and neopentyl complexes. The last of these can activate H2 to make a rare example of a titanium chlorohydride, with the metal pincer fragment staying attached. EPR has been used to characterise the paramagnetic complexes and locate their electron spins, which is further validated with DFT calculations. This opens the door for this archetypical pincer ligand to be used with early transition metals.

Amidosquaramides - a new anion binding motif with pH sensitive anion transport properties.

Stimuli responsive anion transport is becoming an important aspect of supramolecular anion recognition chemistry. Herein, we report the synthesis of a family of anion receptors that incorporate a new anion binding motif, amidosquaramides. We show using experimental and computational methods that these receptors have pKa values close to physiological pH but also display intramolecular H-bonding interactions that affect anion recognition. Moreover, moderate activity in a Cl-/NO3- exchange assay is observed at physiological pH that can be effectively 'switched on' when repeated under acidic conditions. The reported findings provide synthetic methods that can be used for the construction of more complex squaramide based anion receptors and also provide insight into the importance of conformational analysis when considering receptor design.

AT2 activation does not influence brain damage in the early phase after experimental traumatic brain injury in male mice.

Antagonism of the angiotensin II type 1 receptor (AT1) improves neurological function and reduces brain damage after experimental traumatic brain injury (TBI), which may be partly a result of enhanced indirect angiotensin II type 2 receptor (AT2) stimulation. AT2 stimulation was demonstrated to be neuroprotective via anti-inflammatory, vasodilatory, and neuroregenerative mechanisms in experimental cerebral pathology models. We recently demonstrated an upregulation of AT2 after TBI suggesting a protective mechanism. The present study investigated the effect of post-traumatic (5 days after TBI) AT2 activation via high and low doses of a selective AT2 agonist, compound 21 (C21), compared to vehicle-treated controls. No differences in the extent of the TBI-induced lesions were found between both doses of C21 and the controls. We then tested AT2-knockdown animals for secondary brain damage after experimental TBI. Lesion volume and neurological outcomes in AT2-deficient mice were similar to those in wild-type control mice at both 24 h and 5 days post-trauma. Thus, in contrast to AT1 antagonism, AT2 modulation does not influence the initial pathophysiological mechanisms of TBI in the first 5 days after the insult, indicating that AT2 plays only a minor role in the early phase following trauma-induced brain damage.

High antimicrobial resistance in urinary tract infections in male outpatients in routine laboratory data, Germany, 2015 to 2020.

BackgroundEvidence on the distribution of bacteria and therapy recommendations in male outpatients with urinary tract infections (UTI) remains insufficient.AimWe aimed to report frequency distributions and antimicrobial resistance (AMR) of bacteria causing UTI in men and to identify risk factors for resistance of Escherichia coli against trimethoprim (TMP) and ciprofloxacin (CIP).MethodsWe conducted a retrospective observational study using routinely collected midstream urine specimens from 102,736 adult male outpatients sent from 6,749 outpatient practices to nine collaborating laboratories from all major regions in Germany between 2015 and 2020. Resistance in E. coli was predicted using logistic regression.ResultsThe three most frequent bacteria were E. coli (38.4%), Enterococcus faecalis (16.5%) and Proteus mirabilis (9.3%). Resistance of E. coli against amoxicillin (45.7%), TMP (26.6%) and CIP (19.8%) was common. Multiple drug resistance was high (22.9%). Resistance against fosfomycin (0.9%) and nitrofurantoin (1.9%) was low. Resistance of En. faecalis against CIP was high (29.3%). Isolates of P. mirabilis revealed high resistance against TMP (41.3%) and CIP (16.6%). The CIP and TMP resistance was significantly higher among bacteria derived from recurrent UTI (p < 0.05). Age ≥ 90 years, recurrent UTI and regions East and South were independently associated with AMR of E. coli against TMP and CIP (p < 0.05).ConclusionThe most frequent UTI-causing pathogens showed highresistance against TMP and CIP, empirical therapy is therefore likely to fail. Apart from intrinsically resistant pathogens, susceptibility to fosfomycin and nitrofurantoin remains sufficient. Therefore, they remain an additional option for empirical treatment of uncomplicated UTI in men.

The State of Microbiology Diagnostic of Prosthetic Joint Infection in Europe: An In-Depth Survey Among Clinical Microbiologists.

Background: This study aims to give an overview on how microbiology diagnosis tests of Prosthetic joint infections (PJI) is performed in Europe, and to explore whether any factor influences the decision on implementing a test. Methods: An extensive online survey of clinical microbiologists from seven European countries (Belgium, Estonia, Germany, Italy, Netherlands, Switzerland, and Spain). Following items were assessed: (i). general information on the laboratory, (ii) preference of the laboratory and clinical microbiologists regarding samples, (iii) transportation and (iv) processing of explanted foreign bodies and tissues and synovial fluid, (v) culture media and culture duration, (vi) reporting (identification and susceptibility testing), and (vii) use of molecular microbiology techniques. Results: Invited were 163 clinical microbiologists. The response rate from each country was above 50% (range 51-78%), except for Germany (36%). Frequent PJI diagnostics were the use of tissue pre-processing (58.1%), culturing synovial fluid in blood culture bottles (45.5%), use of sonication for processing explanted prosthesis (56.8%), reporting the presence of synovial leukocyte counts (67%), use of blood aerobic and anaerobic agar (97.7%), and enrichment media thioglycolate (69.3%). The most common incubation time of the culture media is 7-14 days (34.1-70.5%). The clinicians were called to report the culture results (80.7%), and to give antibiotic recommendation (67%). Conclusion: There are common practices in processing PJI samples and reporting results, which is promising for harmonization of PJI diagnostic in the future. However, variation in diagnostic tests should also be considered in interpreting and comparing clinical microbiology results.