Specific Antibiotic Treatment Research Articles

Clinical analysis of colistin sulfate in the treatment of pneumonia caused by carbapenem-resistant Gram-negative bacteria.

Multidrug-resistant Gram-negative bacteria, exacerbated by excessive use of antimicrobials and immunosuppressants, are a major health threat. To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia, and to provide theoretical reference for clinical diagnosis and treatment. This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022. After bacteriological culture, the patients' airway secretions were collected to confirm the presence of Gram-negative bacilli. The patients were divided into the experimental and control groups according to the medication used. The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous, nebulization, or intravenous combined with nebulization, with a daily dosage of 1.5-3.0 million units. The control group consisted of 26 patients who received standard dosages of other antibiotics (including sulbactam sodium for injection, cefoperazone sodium sulbactam for injection, tigecycline, meropenem, or vaborbactam). Of the 28 patients included in the research group, 26 patients showed improvement, treatment was ineffective for two patients, and one patient died, with the treatment efficacy rate of 92.82%. Of the 26 patients in the control group, 18 patients improved, treatment was ineffective for eight patients, and two patients died, with the treatment efficacy rate of 54.9%; significant difference was observed between the two groups (P < 0.05). The levels of white blood cell (WBC), procalcitonin (PCT), and C-reactive protein (CRP) in both groups were significantly lower after treatment than before treatment (P < 0.05), and the levels of WBC, PCT, and CRP in the research group were significantly lower than those in the control group (P < 0.05). Compared with before treatment, there were no significant changes in aspartate aminotransferase, creatinine, and glomerular filtration rate in both groups, while total bilirubin and alanine aminotransferase decreased after treatment (P < 0.05) with no difference between the groups. In patients with good clinical outcomes, the sequential organ failure assessment (SOFA) score was low when treated with inhaled polymyxin sulfate, and specific antibiotic treatment did not improve the outcome. Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes. Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable. Moreover, the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions, providing new ideas for clinical administration.

Abstract 3733: Gut microbiota-dependent bile acidtaurodeoxycholic acid, TDCAfacilitates anti-tumor immune responses by modulating cytotoxic CD8 T cell immunity

Abstract Gut microbiota are critical for effective immune checkpoint blockade therapy (ICT) for cancer. However, the underlying mechanisms by which gut microbiota and/or microbiota-derived metabolites augment antitumor response are largely unknown. Here, we utilized a preclinical melanoma (B16-F10) model and treated groups of mice (Jackson, C57BL/6J, female, 6-8 wks, n=14-26 per group) with seven distinct antibiotic treatments to induce unique gut microbiomes and metabolomes. Mice were then treated with ICT (anti-PD-1 and anti-CTLA-4), resulting in markedly heterogeneous tumor phenotypes (tumor volume and weight) as dictated by the specific antibiotic treatment. Using machine learning (e.g. random forest classifier), we identified metabolite candidates most strongly associated with ICT response (i.e. tumor volume and weight).One metabolite candidate, the bile acid taurodeoxycholic acid, TDCA, had previously been identified by my group as associated with anti-PD-1/anti-CTLA-4 response in human melanoma patients (PMID 28923537). Administration of TDCA alone is sufficient to overcome antibiotic-induced ICT hyporesponsiveness in mice. Utilizing both in vitro/ex vivo immune cell assays and in vivo preclinical models, we have validated that TDCA treatment directly boosted the antitumor cytotoxic CD8+ T cell responses (i.e. IFN-gamma production, anti-tumor cytotoxicity, tumor growth, etc.) without affecting innate immune responses. Bulk RNAseq of CD8 T cell analysis indicated that TDCA modulate CD8 T cell function through IFN pathway. Together, our findings suggest that the gut microbial metabolite TDCA could promote immunotherapy efficacy through regulation of CD8+ T cell immunity and has the potential to be utilized as a novel therapeutic agent to enhance ICT efficacy. Citation Format: Wenng li, Hesuiyuan Wang, Laura Coughlin, Nicole Poulides, Priscilla Del Valle, Jake Lichterman, Xiaowei Zhan, Chen Liao, Suzette N. Palmer, Xin Li, Andrew Y. Koh. Gut microbiota-dependent bile acidtaurodeoxycholic acid, TDCAfacilitates anti-tumor immune responses by modulating cytotoxic CD8 T cell immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3733.

MetaQuad: shared informative variants discovery in metagenomic samples.

Strain-level analysis of metagenomic data has garnered significant interest in recent years. Microbial single nucleotide polymorphisms (SNPs) are genomic variants that can reflect strain-level differences within a microbial species. The diversity and emergence of SNPs in microbial genomes may reveal evolutionary history and environmental adaptation in microbial populations. However, efficient discovery of shared polymorphic variants in a large collection metagenomic samples remains a computational challenge. MetaQuad utilizes a density-based clustering technique to effectively distinguish between shared variants and non-polymorphic sites using shotgun metagenomic data. Empirical comparisons with other state-of-the-art methods show that MetaQuad significantly reduces the number of false positive SNPs without greatly affecting the true positive rate. We used MetaQuad to identify antibiotic-associated variants in patients who underwent Helicobacter pylori eradication therapy. MetaQuad detected 7591 variants across 529 antibiotic resistance genes. The nucleotide diversity of some genes is increased 6 weeks after antibiotic treatment, potentially indicating the role of these genes in specific antibiotic treatments. MetaQuad is an open-source Python package available via https://github.com/holab-hku/MetaQuad.

Conservative Management First Strategy in Aortic Vascular Graft and Endograft Infections

The aim of this study was to describe and present the outcomes of a specific treatment protocol for aortic vascular graft and endograft infections (VGEIs) without explantation of the infected graft. This was a retrospective, observational single centre cohort study carried out between 2012 and 2022 at a tertiary hospital. An aortic VGEI was defined according to the Management of Aortic Graft Infection Collaboration (MAGIC) criteria. Fitness for graft excision was assessed by a multidisciplinary team and included an evaluation of the patient's general condition, septic status, and anatomical complexity. Antimicrobial treatments were individualised. The primary outcome was survival at the last available follow up; secondary outcomes were antimicrobial treatment duration, infection eradication, treatment failure despite antimicrobial treatment, and the development of aortic fistulation. Fifty patients were included in the study, of whom 42 (84%) had had previous endovascular repair. The median patient age was 72 years (range 51 - 82 years) and median duration of treatment with antimicrobials was 18 months (range 1 - 164 months). Kaplan-Meier analysis estimated the 30 day survival to be 98% (95% confidence interval [CI] 96 - 100), the one year survival rate to be 88% (95% CI 83.4 - 92.6), and the three year survival rate to be 79% (95% CI 72.7 - 84.7). Twenty-four (48%) patients were able to discontinue antibiotic treatment after a median of 16 months (range 4 - 81 months). When categorised according to infected graft location, deaths occurred in four (40%) patients with thoracic, two (40%) with paravisceral, seven (30%) with infrarenal VGEIs, and in one (25%) patient with an aorto-iliac VGEI; no (0%) patient with a thoraco-abdominal VGEI died. Identifying the microbiological aetiology in patients with aortic VGEI enables individualised, specific antibiotic treatment, which may be useful in patients with a VGEI excluded from surgery. This single centre retrospective analysis of patients with VGEIs without fistula selected for conservative treatment suggests that conservative management of aortic VGEIs with targeted antibiotic therapy without graft excision is potentially effective, and that antimicrobial treatment will not necessarily be needed indefinitely.

Therapeutic Options and Outcomes for the Treatment of Children with Gram-Positive Bacteria with Resistances of Concern: A Systematic Review.

Methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative Staphylococci (MR-CoNS), and vancomycin-resistant Enterococci (VRE) are increasing worldwide and represent a threat for the limited treatment options in pediatric patients and neonates compared to adults. Recommendations in pediatrics are mainly extrapolated from adults' studies. A literature search for the treatment of these pathogens in children (<18 years old) was conducted in Embase, MEDLINE, and Cochrane Library. Studies reporting data on single-patient-level outcomes related to a specific antibiotic treatment for multidrug resistant (MDR) Gram-positive bacterial infection in children were included. Studies reporting data from adults and children were included if single-pediatric-level information could be identified (PROSPERO registration: CRD42022383867). The search identified 11,740 studies (since January 2000), of which 48 fulfilled both the inclusion and the exclusion criteria and were included in the analysis: 29 for MRSA, 20 for VRE, and seven for MR-CoNS. Most studies were retrospective studies. Vancomycin was mainly used as a comparator, while linezolid and daptomycin were the most studied antimicrobials showing good efficacy. Linezolid showed a safety and efficacy profile in a neonatal setting; daptomycin is increasingly used for MRSA, but the evidence is scarce for VRE.

Role of Surgery in Brucella Spondylodiscitis: An Evaluation of 28 Patients.

Background A limited number of studies are available in the literature on the surgical treatment of brucellosis-related spondylodiscitis. This study aimed to define and discuss the role of surgery in brucellosis-related spondylodiscitis. Methodology A total of 28 patients who underwent surgical treatment due to brucellosis-related spondylodiscitis between February 2021 and August 2022 were included in this study. Medical records, radiological images, and laboratory data were collected. Surgical results were evaluated according to the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels, clinical findings, postoperative radiological imaging findings, and complications were evaluated. Results In total, 16 of the patients included in the study were male and 12 were female, with a mean age of 56.4 ± 7.2 years. The mean follow-up duration was 11.8 ± 5.4 months. Brucellosis involvement was in the lumbosacral region in all patients. Overall, 21 patients had a neurological deficit in the preoperative period. Posterior stabilization and fusion were done in 20 (71.4%) patients, while simple laminectomy (decompression) and debridement were done in eight (28.6%) patients. There was a decrease in the pain in the lower back and leg in all patients in the postoperative period. Neurological recovery was achieved in 18 patients with a neurological deficit. Two patients underwent wound drainage in the postoperative period.The patient who had morbid obesity and comorbidities died in the postoperative period. ESR and CRP levels returned to normal at the end of the six-month follow-up. There was a significant recovery in VAS and ODI scores (p < 0.05). In total, 24 (85.4%) patients were considered fully recovered both radiologically and clinically at the end of the follow-up. Conclusions Although long-term and specific antibiotic treatment constitute the main treatment in brucellosis-related spondylodiscitis, debridement, decompression, and stabilization (when required) of infection with a focus on neurological deficits and instability formation and non-stop severe pain are effective and safe treatment options.

Successful treatment of infectious endocarditis-associated glomerulonephritis during active hepatitis C infection: a case report

BackgroundHepatitis C virus (HCV) may play a pathogenic role in several forms of immune complex glomerulonephritis (GN). We present a patient whose initial clinical presentation instilled suspicion of HCV-related renal involvement. Yet, histopathologic data oriented towards a different diagnosis.Case presentationA 68-year old man presented with kidney dysfunction, cryoglobulins, low C4 level, high HCV—RNA and cutaneous vasculitis. The first hypothesis was a hepatitis C-related cryoglobulinemic glomerulonephritis. Renal biopsy revealed endocapillary and mesangial cells hypercellularity with complement C3 and IgM deposits. The echocardiography showed an infectious endocarditis (IE) on aortic valve. Appropriate antibiotic therapy and a prosthetic valve replacement were performed, obtaining recovery of renal function.ConclusionHCV infection may be linked to multiple renal manifestations, often immune-complex GN such as cryoglobulinemic membrano-proliferative GN. Renal disease due to IE is usually associated to focal, segmental or diffuse proliferative GN, with prominent endocapillary proliferation. The most common infectious agents are Staphylococcus aureus and Streptococcus species.This case report may be relevant because the renal dysfunction was highly suggestive of a cryoglobulinemic GN on a clinical ground, but the histologic pattern after performing the renal biopsy oriented towards a different cause of the underlying disease, that required a specific antibiotic treatment. The renal biopsy is always required to confirm a clinical suspicious in patients affected by multiple comorbidities.

Burden and mortality of sepsis and septic shock at a high-volume, single-center in Vietnam: a retrospective study

ABSTRACT Background Sepsis and septic shock have high mortality rates and often require a prolonged hospital stay. Patient outcomes may vary according to multiple factors. We aim to determine the prevalence of antimicrobial resistance and factors associated with mortality and hospital stay. Methods Clinical and microbiological data of patients with sepsis or septic shock were retrospectively collected for 15 months. Patients with negative blood cultures and patients that did not meet the SEPSIS 3 criteria were excluded. Results We included 48 septic shock and 28 septic patients (mean APACHE II 20.32 ± 5.61 and mean SOFA 9.41 ± 3.17), with a mean age of 60.5 ± 16.8 years and 56.6% males. WBCs, neutrophils, INR, and fibrinogen levels were significantly associated with mortality. 59.5% of the cultured bacteria were gram-negative (most common E. coli) and 27.8% were gram-positive (most common S. aureus), while 7.6% were other types of bacteria and 5.1% were fungi. Resistance patterns to gram-negative were varying, and resistance to piperacillin/tazobactam, carbapenems, and aminoglycosides were from 60% to 100% (A. baumanii), while they were highly sensitive to Colistin. E. coli was also resistant to ceftriaxone (77.8%) and sulbactam/cefoperazone (44.4%). Resistance rates for Gram-positives were high, from 86% to 100% for oxacillin, while for vancomycin, teicoplanin, and linezolid, they were often low but arrived up to 42.8%. According to our logistic regression analysis, patients over 65 year-old and those who received corticosteroids had a significantly increased risk of in-hospital mortality (OR: 4.0; OR: 4.8). Conclusion Sepsis still poses a significant threat to patients’ health, even when positive blood culture results allow the administration of specific antibiotic treatment.

Therapeutic Options and Outcomes for the Treatment of Neonates and Preterms with Gram-Negative Multidrug-Resistant Bacteria: A Systematic Review.

(1) Background: Infections caused by multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacteria represent a challenge in the neonatal population due to disease severity and limited therapeutic possibilities compared to adults. The spread of antimicrobial resistance and drug availability differ significantly worldwide. The incidence of MDR bacteria has constantly risen, causing an increase in morbidity, mortality, and healthcare costs in both high-income (HIC) and low- and middle-income countries (LMIC). Therefore, more evidence is needed to define the possible use of newer molecules and to optimize combination regimens for the oldest antimicrobials in neonates. This systematic review aims to identify and critically appraise the current antimicrobial treatment options and the relative outcomes for MDR and XDR Gram-negative bacterial infections in the neonatal population. (2) Methods: A literature search for the treatment of MDR Gram-negative bacterial infections in neonates (term and preterm) was conducted in Embase, MEDLINE, and Cochrane Library. Studies reporting data on single-patient-level outcomes related to a specific antibiotic treatment for MDR Gram-negative bacterial infection in children were included. Studies reporting data from adults and children were included if single-neonate-level information could be identified. We focused our research on four MDROs: Enterobacterales producing extended-spectrum beta-lactamase (ESBL) or carbapenemase (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii. PROSPERO registration: CRD42022346739 (3) Results: The search identified 11,740 studies (since January 2000), of which 22 fulfilled both the inclusion and exclusion criteria and were included in the analysis. Twenty of these studies were conducted in LMIC. Colistin is the main studied and used molecule to treat Gram-negative MDR bacteria for neonate patients in the last two decades, especially in LMIC, with variable evidence of efficacy. Carbapenems are still the leading antibiotics for ESBL Enterobacterales, while newer molecules (i.e., beta-lactam agents/beta-lactamase inhibitor combination) are promising across all analyzed categories, but data are few and limited to HICs. (4) Conclusions: Data about the treatment of Gram-negative MDR bacteria in the neonatal population are heterogeneous and limited mainly to older antimicrobials. Newer drugs are promising but not affordable yet for many LMICs. Therefore, strategies cannot be generalized but will differ according to the country’s epidemiology and resources. More extensive studies are needed to include new antimicrobials and optimize the combination strategies for the older ones.

Antibiotic use attributable to specific aetiologies of diarrhoea in children under 2 years of age in low-resource settings: a secondary analysis of the MAL-ED birth cohort

ObjectiveTo quantify the frequency of antibiotic treatments attributable to specific enteric pathogens due to the treatment of diarrhoea among children in the first 2 years of life in low-resource settings.DesignSecondary...

Fluoroquinolones and Other Antibiotics Redeemed for Cystitis-A Swedish Nationwide Cohort Follow-Up Study (2006-2018).

Background: Antibiotics are commonly prescribed for outpatient management of cystitis. Previous evidence suggests that certain factors likely beyond the infection seem to influence the choice of antimicrobial treatment. However, studies on the specific antibiotic treatments for cystitis are lacking. This study aimed to explore the antibiotic treatments for cystitis using nationwide primary healthcare data and investigate if factors beyond the infection could be associated with fluoroquinolone treatment. Methods: This nationwide follow-up cohort study consisted of 352,507 women with cystitis. The primary aim was to investigate what specific classes of antibiotics were redeemed by patients within five days from the cystitis diagnosis. Each patient could only be included once. Logistic regression models were also used to examine the relationship between fluoroquinolone (FQ) treatment, parity, and sociodemographic factors. Results: In total, 192,065 antibiotic prescriptions were redeemed. Pivmecillinam (58.4%) followed by nitrofurantoin (22.2%), trimethoprim (12.0%), fluoroquinolone (5.6%), and cephalosporins (1.5%) were the most redeemed antibiotics. Sociodemographic factors were weakly associated with fluoroquinolone treatment; young age was inversely associated with fluoroquinolone treatment. Parity and cervical cancer history were not associated with fluoroquinolone treatment. The proportion of fluoroquinolone and trimethoprim treatments decreased over time, while pivmecillinam and nitrofurantoin increased. Conclusions: The treatment trends of antibiotics redeemed within five days from a cystitis diagnosis were similar to the national surveillance program of these antibiotics (not diagnosis linked). Fluoroquinolones were weakly associated with sociodemographic factors, which likely is only of historical relevance.

Management and outcome of spinal implant-associated surgical site infections in patients with posterior instrumentation: analysis of 176 cases.

The management of implant-associated surgical site infections (SSI) in patients with posterior instrumentation is challenging. Evidence regarding the most appropriate treatment and the need for removal of implants is equivocal. We sought to evaluate the management and outcome of such patients at our institution. We searched our prospectively documented databases for eligible patients with posterior spinal instrumentation, excluding the cervical spine (January 2008-June 2018). Patient files were reviewed, demographic data and treatment details were recorded. Patient-reported outcome (PRO) was assessed with the Core Outcome Measures Index (COMI) preoperatively and postoperatively at 3 and 12months. A total of 170 patients underwent 210 revisions for 176 SSIs. Two-thirds presented within four weeks (105/176, 59.7%, median 22.5d, 7d-11.1y). The most common pathogens were Staphylococcus aureus (n = 79/210, 37.6%) and Staphylococcus epidermidis (n = 56/210, 26.7%). Debridement and implant retention was performed in 135/210 (64.3%) revisions and partial replacement in 62/210 (29.5%). In 28/176 SSI (15.9%), persistent infection required multiple revisions (≤ 4). Surgery was followed by intravenous and oral antimicrobial treatment (10-12w). In 139/176 SSIs (79%) with ≥ 1y follow-up, infection was cured in 115/139 (82.7%); relapse occurred in 9 (relapse rate: 5.1%). Two patients (1.4%) died. COMI decreased significantly (8.2 ± 1.5 vs. 4.8 ± 2.9, p < 0.0001) over 12months. 72.7% of patients were (very) satisfied with their care. Patients with SSI after posterior (thoraco-)lumbo(-sacral) instrumentation can be successfully treated in most cases with surgical and specific antibiotic treatment. An interdisciplinary approach is recommended. Loose implants should be replaced. In some cases, multiple revisions may be necessary. Patient outcomes were satisfactory.

Corticosteroids in tuberculous pericarditis whit severe pericardial effusion to avoid constriction: a retrospective study in HIV-negative population

Abstract The role of corticosteroids in the treatment of tuberculous aetiology pericarditis without human immunodeficiency virus (HIV) is not well defined. Is unclear if associating corticoids to regular antibiotic therapy for tuberculosis, can prevent the progression of a severe pericardial effusion to constrictive pericarditis. Despite that, in countries where tuberculosis is an endemic disease and mostly it's not related to HIV, the use of corticosteroids is a common practice, as a part of a strategy to avoid progression of a severe pericardial effusion to a constrictive pericarditis. Our aim is to describe the clinical course of the patients with severe pericardial effusion of tuberculous aetiology and no echocardiographic sings of constriction, distinguishing those who used corticosteroids from those who didn't. We conducted a retrospective study, analyzing the clinical files of 40 patients treated in one hospital in a 5 years period (2016–2021). All of these patients were diagnosed whit severe pericardial effusion of tuberculous aetiology and no signs of constrictive pericarditis, they all finished their specific antibiotic treatment protocol according national guidelines and had at least 2 years of clinical follow from the time of the diagnosis. We found that the mean age was 54 years, 55% were men and 45% women. The mean follow up was 2.6 years. In all patients pericardial drainage was preformed, 60.5% using closed pericardiocentesis and 39.5% using open surgical techniques. 22 patients (55%) received prednisone that was initiated whit a dose of 1mg/kg daily that was reduced weekly in order to complete a 2 month cycle. The other 18 patients (45%) didn't received corticosteroids. In the prednisone group, 3 patients develop constrictive pericarditis during the time of follow up (13.6% of the prednisone group) while 7 patients of the non-corticosteroids group (38.8%) develop constrictive pericarditis. These retrospective study shows that there is a potential reduction in the progression to constrictive pericarditis whit the use of prednisone in HIV negative patients whit severe pericardial effusion of tuberculous aetiology, we need to perform prospective, controlled, blind and multicenter studies, designed to evidence the real effect of these strategy. Funding Acknowledgement Type of funding sources: None. Cases of contriction in both groups

Warm Weather and Surgical Site Infections: A Meta-analysis.

Background:Seasonal variability, in terms of warm weather, has been demonstrated to be a significant risk factor for surgical site infections (SSIs). However, this remains an underexposed risk factor for SSIs, and many clinicians are not aware of this. Therefore, a systematic review and meta-analysis has been conducted to investigate and quantify this matter.Methods:Articles were searched in Embase, Medline Ovid, Web of Science, Cochrane Central, and Google Scholar, and data were extracted from relevant studies. Meta-analysis used random effects models to estimate and compare the pooled odds ratios (OR) and corresponding confidence intervals (CIs) of surgery performed during the warmest period of the year and the colder period of the year.Results:The systematic review included 20 studies (58,599,475 patients), of which 14 studies (58,441,420 patients) were included for meta-analysis. Various types of surgical procedures across different geographic regions were included. The warmest period of the year was associated with a statistically significant increase in the risk of SSIs (OR 1.39, 95%CI: [1.34–1.45], P < 0.0001). Selection of specific types of surgical procedures (eg, orthopedic or spinal surgery) significantly altered this increased risk.Conclusions:The current meta-analysis showed that warm weather seasons are associated with a statistically significant risk increasement of 39% in developing SSIs. This significant risk factor might aid clinicians in preoperative patient information, possible surgical planning adjustment for high risk patients, and potentially specific antibiotic treatments during the warmer weather seasons that could result in decrease of SSIs.

DOP73 Antibiotic use differentially affects the risk of antidrug antibody formation during anti-TNFα therapy in Inflammatory Bowel Disease

Abstract Background Anti-drug antibodies (ADA) to anti-TNF therapy drive loss of response to treatment. Links between intestinal microbial composition and response to anti-TNF therapy were demonstrated, and antibiotic use during anti-TNF therapy reduced the risk of ADA formation. Here, we aimed to assess the possible implications of specific antibiotic treatments on ADA formation in patients with inflammatory bowel disease (IBD) patients. Methods We performed a retrospective analysis of data from three health maintenance organizations, covering 89% of the Israeli population. All patients with IBD and available ADA levels were included. Survival analysis using Kaplan-Meier and multivariate Cox proportional hazards regression with drug use as time varying covariates methods were used to assess the association between specific antibiotic use and ADA development. C57BL and germ free mice were treated with respective antibiotics followed by immunization with infliximab. ADA were assessed after 14 days. Results We analyzed 1,946 patients treated with anti-TNF. Positive ADAs were detected in 363 patients (18.6%). Age, gender and concomitant use of immunomodulators where comparable in patients who eventually developed ADAs or not. However, infliximab and not adalimumab therapy, previous anti-TNF therapy and higher baseline C-reactive protein levels were significantly associated with ADA development in univariate analysis. Kaplan-Meier curves of prior antibiotic use demonstrated significant hazard of ADA development in patients who used cephalosporins or penicillins with beta-lactamase inhibitors (BLI) and reduced risk with prior use of fluoroquinolones, macrolides or metronidazole (Figure 1) with early risk divergence for most classes. Multivariable Cox proportional hazards model adjusted for multiple factors associated with ADA development was overall consistent with Kaplan-Meier estimates (Figure 2). In mice exposed to infliximab, increased ADA production by cefuroxime treatment and a non-significant reduction following azithromycin treatment was noticed (Figure 3). Germ free mice produced no ADA. Figure 1: Kaplan-Meier curves of cumulative risk of ADA development for prior use of specific antibiotics. P value for the log rank test is presented in each plot. Figure 2: Multivariable-adjusted HR with 95% CI of ADA for use of various antibiotic classes during anti-TNF therapy. Figure 3: Mean ADA levels in mice treated with anti-TNF and prior cefuroxime, azithromycin, or no antibiotic Conclusion ADA production is microbial dependent. The risk of ADA development during anti-TNF therapy can possibly be reduced by avoidance of cephalosporins and penicillins with BLI, or possibly reduced by treatment with fluoroquinolones or macrolides.

Legionella Pneumonia on Point-of-care Ultrasound in the Emergency Department: A Case Report.

IntroductionLegionella is an uncommon, atypical organism that can cause community-acquired pneumonia. Commonly associated with high fevers, gastrointestinal symptoms, and hyponatremia, it can be easily overlooked, especially during the coronavirus disease of 2019 (COVID-19) pandemic. Legionella has specific antibiotic treatment that will improve outcome; thus, its recognition is important.Case ReportWe present a case of Legionella pneumonia in a man presenting with shortness of breath and fever. The patient’s initial chest radiography was negative. With the use of point-of-care ultrasound (POCUS) the changes of atypical pneumonia could be seen. Ultimately Legionella was confirmed with urine antigen testing, and appropriate antibiotic treatment was started.DiscussionGiven the increased awareness of COVID-19 it is important to consider a broad differential with respiratory illness. Legionella pneumonia on POCUS is consistent with atypical pneumonia descriptions on ultrasound. Point-of-care ultrasound can be used to diagnose atypical pneumonia, specifically caused by Legionella in our case.ConclusionLegionella is evident on POCUS but is difficult to distinguish from other infections with POCUS alone. One should consider Legionella if POCUS is positive for signs of atypical infection.

Genomic Characterization of a New Biofilm-Forming and Adhesive ST398 Human-Adapted MSSA Lineage Causing Septic Knee Arthritis Following Surgical Reconstruction.

Methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen commonly found in bone and joint infections, including septic arthritis. S. aureus virulence and the frailty of affected patients can cause several complications; a prompt and specific antibiotic treatment can positively affect the outcome of patients. We carried out an in-depth genomic characterization by Illumina whole genome sequencing and bioinformatics of two biofilm-producing M1 and M2 ST398 MSSA causing septic knee arthritis not-responding to antimicrobial therapy. The strains were characterized for antibiotic resistance, biofilm and adhesive properties as well as genomics, single nucleotide polymorphism phylogeny, resistomics and virulomics. Our results showed that M1 and M2 MSSA were ST398-t1451-agrI-Cap5, susceptible to cefoxitin and resistant to erythromycin and clindamycin, traits consistent with the lack of the SCCmec-locus and the presence of the sole blaZ and ermT. Furthermore, M1 and M2 were biofilm-producing and largely potentially adhesive strains, as indicated by the adhesion gene profile. Our data characterized a new human-adapted ST398 MSSA lineage, representing a “fusion” between the human-animal independent ST398 and the Livestock Associated (LA) ST398 lineages, forming biofilm and genomically predicted high adhesive, characterized by different genomic adaptation conferring a great ability to adhere to the host’s extracellular matrix causing septic knee arthritis.

Is the term “anti-anaerobic” still relevant?

For decades, the term “anti-anaerobic” has been commonly used to refer to antibiotics exhibiting activity against anaerobic bacteria, also designated as anaerobes. This term is used in various situations ranging from infections associated with well-identified pathogens like Clostridioides difficile, or Fusobacterium necrophorum in Lemierre’s syndrome, that require specific antibiotic treatments to polymicrobial infections generally resulting from the decreased permeability of anatomical barriers (e.g., intestinal translocation and stercoral peritonitis) or infectious secondary localizations (e.g., brain abscess and infectious pleurisy). In these cases, the causal bacteria generally remain unidentified and the antimicrobial treatment is empirical. However, major progress in the knowledge of human bacterial microbiotas in the last 10 years has shown how diverse are the species involved in these communities. Here, we sought to reappraise the concept of anti-anaerobic spectrum in the light of recent advances in the microbiota field. We first highlight that the term anaerobic itself does not represent the tremendous diversity of the bacteria it spans, and then we stress that the antibiotic susceptibility profiles for most anaerobic bacteria remain unaddressed. Furthermore, we provide examples challenging the relevance of the “anti-anaerobic” spectrum from a clinical and ecological perspective.

Yoğun Bakımda Gelişen Karbapeneme Dirençli Acinetobacter baumannii İnfeksiyonlarında Mortalite ile İlişkili Faktörler: Prospektif Gözlem Çalışması

Introduction: Management of carbapenem resistant Acinetobacter baumannii infections in intensive care units is challenging because of few treatment options and poor outcomes. In order to contribute to patients’ survival, the factors related to mortality in these infections were evaluated in this study. Materials and Methods: In the 6-month study period, we included 60 patients with carbapenem resistant A. baumannii infections (45 ventilator associated pneumonia and 15 bacteremia) in two intensive care units of our hospital. We collected data of the patients prospectively. We noted demographic features of patients, Acute Physiology and Chronic Health Evaluation (APACHE II) , Sequential Organ Failure Assessment (SOFA), Clinical Pulmonary Infection Score (CPIS), Acute Kidney Injury (AKIN) scores, antibiotic treatments, clinical and microbiological outputs, and mortality rates during treatment and on the 30th day. Results: We observed that infections appeared at mean 11th day of the patients’ stay in the intensive care unit. Carbapenem resistant A. baumannii isolates were highly resistant to antibiotics except colistin. Only 9% of the patients had proper empirical treatment. Twenty five percent of the patients were dead before having a specific antibiotic treatment. Crude mortality rate was 66.7%, and 30th day mortality was 71.7%. The patients who had colistin and tigecycline combination had higher survival rates, but it was statistically insignificant. In univariate analysis high SOFA score (p= 0.0001), high procalcitonin level (p= 0.01), septic shock (p= 0.005), renal insufficiency (p= 0.005), rheumatological disease (p= 0.03) were related to higher mortality. We detected high SOFA score on the first day of infection as the only mortality related factor in multivariate analysis (p= 0.012). The patients who had higher mortality were those with delayed (&gt; 3 days) proper antimicrobial treatment (p= 0.03). Conclusion: In our study, the high SOFA score on the first day of infection in intensive care units was found as a risk factor for mortality. We suggest that prompt administration of the proper antibiotic treatment to the patients who have risk factors for carbapenem-resistant A. baumannii infection can contribute to survival.

A case of purple urine bag syndrome in an elderly patient

Purple urine bag syndrome is a rare condition that occurs predominantly in the elderly, immobilized and bearer of chronic bladder catheter. It is a phenomenon usually associated with urinary tract infection, particularly in the presence of high bacterial load. The presence of alkaline urine, constipation, high-protein diet and dehydration are predisposing factors. In most cases it is an asymptomatic condition. We described the case of an elderly patient admitted to the geriatric Department in which purple urine was found in the urine collection bag. The culture of urine showed the presence of infection with Klebsiella pneumoniae. Targeted antibiotic treatment and proper hydration determined the resolution of the phenomenon and the resolution of the infection. Although it is an alarming phenomenon due to the particularity of the color of the urine, it is a treatable and solvable condition with an adequate specific antibiotic treatment. Prevention measures are equally effective and consist in eliminating the risk factors for this condition.