Broad-spectrum Antibiotic Therapy Research Articles

Syndrome of Boerhaave and Pregnancy: A Case Report

The syndrome of Boerhaave is a rare affection, it’s is characterized by the spontaneous transmural rupture of the esophagus. The classic presentation of Boerhaave syndrome is characterized by Mackler's triad, consisting of chest pain, vomiting, and subcutaneous emphysema. We report a case of spontaneous rupture of the oesophagus in a three-month pregnant woman, further to incoercible vomiting. The good clinical tolerance of the patient has allowed a medical care with strict monitoring, parenteral food and broad-spectrum antibiotic therapy. The surgery, usually indicated in this pathology, was not realized in this case. The obstetric and neonatal future was favorable. We discuss the diagnostic difficulties, the modalities of cares as well as the prognosis of such a pathology.

Group B Streptococcus Meningitis in an Adult Woman with Type 2 Diabetes and Ethmoid Roof Defect. Impact on "frontal" Cognitive Functions.

Community-acquired bacterial meningitis in adults represents one of the most severe infectious diseases worldwide with potentially life-threatening medical complications. Several infectious agents can cause acute meningitis. Although group B Streptococcus is more prevalent in newborns, infection can also lead to meningitis in older adults, particularly those with underlying health issues. A 53-year-old woman with a body mass index of 28.7 kg/m2, type 2 diabetes mellitus, and dyslipidaemia presented to the emergency department of Santa Maria della Stella Hospital (Orvieto, Italy) with confusion, low-grade fever, echolalia, and hyperglycaemia. Computed tomography scans of the brain revealed a hypodensity in the left anterior frontal lobe and an osteodural defect of the rhinobase. Meningitis was suspected and empiric broad-spectrum antibiotic therapy with corticosteroids and insulin were administered while the results of the cerebrospinal fluid analysis confirmed the diagnosis of group B Streptococcus meningitis. Repeat imaging at 48 hours revealed enlargement of the hypodense lesion. The frontal assessment battery indicated deficits in executive functions. Prompt treatment led to rapid clinical improvement. Following the restoration of euglycemic status and hemodynamic stabilization, a follow-up magnetic resonance imaging confirmed the ischaemic lesion and showed cerebrospinal fluid in the sella turcica. The patient was then transferred to neurorehabilitation. The complex interactions among multiple risk factors resulted in an atypical clinical case of group B Streptococcus meningitis, which was promptly treated with empiric antibiotic therapy to mitigate neurocognitive deficits. Group B Streptococcus can cause meningitis in adults with poorly controlled type 2 diabetes mellitus and should be promptly treated with empiric broad-spectrum antibiotics.An osteodural defect of the ethmoid roof together with idiopathic intracranial hypertension may result in empty sella turcica and CSF rhinorrhoea, promoting the dissemination of the pathogen.Meningitis patients with pre-existing diabetic cerebral vasculopathy may develop cerebrovascular complications and cognitive impairments.

Wedge Resection and Optimal Solutions for Invasive Pulmonary Fungal Infection and Long COVID Syndrome—A Case Report and Brief Literature Review

A rise in fungal infections has been observed worldwide among patients with extended hospital stays because of the severe infection caused by the new coronavirus pandemic. A 62-year-old female patient was admitted with a severe form of Coronavirus disease 2019 (COVID-19) and spent four weeks in the intensive care unit (ICU) requiring mechanical ventilation support before being moved to a tertiary hospital for further testing. Aspergillus fumigatus filamentous fungus, Candida spp., and positive bacteriology for multidrug-resistant Klebsiella pneumoniae and Proteus mirabilis were identified by bronchial aspirate cultures. The patient’s progress was gradually encouraging while receiving oral antifungal and broad-spectrum antibiotic therapy along with respiratory physical therapy; but ultimately, thoracic surgery was necessary. Long-lasting tissue damage and severe, persistent inflammatory syndrome were the two main pathophysiological mechanisms that led to significant outcomes regarding lung lesions that were rapidly colonized by fungi and resistant flora, cardiac damage with sinus tachycardia at the slightest effort, and chronic inflammatory syndrome, which was characterized by marked asthenia, myalgias, and exercise intolerance.

How xylitol, gluten, and lactose change human gut microbiota Escherichia coli and Lactobacillus rhamnosus GG biofilm

The human gut microbiota is composed of many viruses, bacteria, and fungi. Escherichia coli representatives are facultative anaerobic bacteria in the colon that play a crucial role in the metabolism of lactose, vitamin synthesis, and immune system modulation. E. coli forms a biofilm on the epithelial cell surface of the intestine that can be modified by diet compounds, i.e., gluten, xylitol, lactose, and probiotics. In the present study, the impact of probiotic-derived Lactobacillus rhamnosus GG strain on non-pathogenic E. coli biofilm was examined. The mono- and multispecies biofilm was also treated with gluten, xylitol, and lactose. We used 96-well plates to obtain biofilm growth. Biofilm was stained using crystal violet. To evaluate the type of interaction in mono- and multispecies biofilm, a new formula was introduced: biofilm interaction ratio index (BIRI). To describe the impact of nutrients on biofilm formation, the biofilm formation impact ratio (BFIR) was calculated. The biofilms formed by both examined species are stronger than in monocultures. All the BIRI values were above 3.0. It was found that the monospecies biofilm of L. rhamnosus is strongly inhibited by gluten (84.5%) and the monospecies biofilm of E. coli by xylitol (85.5%). The mixed biofilm is inhibited by lactose (78.8%) and gluten (90.6%). The relations between bacteria in the mixed biofilm led to changes in biofilm formation by E. coli and L. rhamnosus GG. Probiotics might be helpful in rebuilding the gut microbiota after broad spectrum antibiotic therapy, but only if gluten and lactose are excluded from diet.

Management of oculo-orbital complications of odontogenic sinusitis in adults.

Introduction: Odontogenic maxillary sinusitis (OMS) is an infectious inflammatory pathology caused by a dental condition. Considering the anatomical relations with the orbit, maxillary sinus infection can easily spread, evolving into severe oculo-orbital complications that can sometimes be life-threatening. Material and methods: We performed a retrospective study of over 2 years, examining the data of 18 patients diagnosed with OMS with oculo-orbital complications. The patients were evaluated regarding their dental history, symptoms, clinical and endoscopic findings, ophthalmologic evaluation, bacteriologic tests, computed tomography (CT) imaging, medical and surgical treatment, and outcomes. Results: The age of the patients was between 24 and 65 years old with an almost equal gender distribution: 10 female and 8 male patients. From the total, 7 patients had type II diabetes, 2 of whom were insulin-dependent, 1 patient had thrombophilia and 2 patients had renal failure with peritoneal dialysis. Regarding the type of oculo-orbital complications, 10 patients were diagnosed with preseptal cellulitis and 8 with orbital cellulitis. Just 5 patients with orbital cellulitis required surgical treatment and orbitotomy was performed, followed by endonasal endoscopic drainage. The evolution after surgical treatment was favorable for all operated patients. Discussions: Oculo-orbital complications of OMS are typically more severe than those of rhinogenic sinusitis because anaerobic bacteria are involved. Immunosuppression represents a favorable environment for the development of OMS and its complications, diabetes being the most common risk factor. A negative prognostic feature is the appearance of ophthalmological symptoms in both eyes, so visual function may be reduced. The treatment of oculo-orbital complications of OMS is urgent and depends on a broad-spectrum antibiotic therapy associated or not with surgical intervention. Conclusions: The diagnosis of oculo-orbital complications of OMS is complex and requires clinical experience as well as extensive medical knowledge to treat both the cause and the consequences of the conditions quickly and effectively. The proper management of oculo-orbital complications is based on a multidisciplinary team: ophthalmology, ENT, dentistry, imaging, and laboratory. Abbreviations: OMS = odontogenic maxillary sinusitis, CT = computed tomography, ENT = ear-nose-throat, MRI = magnetic resonance imaging, HNS = head and neck surgery.

Fournier's Gangrene in 21 Years Old Female: A Case Report

Introduction: Fournier's gangrene, also known as gangrene of the genital region, is an uncommon and rapidly advancing form of necrotizing fasciitis that affects the genitals. The severity and mortality of the disease are dependent upon the overall health status of the patient at the time of diagnosis and the speed at which the infection spreads.
 Case presentation: An unmarried 21-year-old woman presented with a persistent discharge of abscesses in the perineal area. The patient came in ambulatory and showed no indicators of heart or lung discomfort. A pelvic examination was performed, and the following observations were made: A visual examination revealed swelling in the vulvar area on both sides, along with an open wound within the swelling measuring 3×3 cm. The wound was discharging reddish, thick, and foul-smelling fluid. A glucose level of +4 was observed in the urine, and a random blood sugar test yielded a value of 324 mg/dl. The patient received wound debridement, excision, and electrocauterization of genital warts, blood sugar monitoring with insulin administration, and a 14-day course of antibiotics. The patient's condition improved, and they were discharged after receiving 14 days of intravenous antibiotic treatment.
 Conclusion: The treatment of Fournier gangrene requires a comprehensive approach that includes intensive systematic management, broad-spectrum antibiotic therapy, and early surgical debridement. This involves removing the necrotic tissues and surgically draining the peritoneum, scrotum, penis, and inguinal regions.

Severe coagulation disorder occurring after broad-spectrum antibiotic therapy in a patient with longstanding infection.

Severe coagulation disorder occurring after broad-spectrum antibiotic therapy in a patient with longstanding infection.

Abstract B090: Gut microbial suppression of epithelial ovarian cancer and attenuation of chemoresistance: opportunity for probiotics in patient care to improve survival

Abstract Up to 80% of ovarian cancer patient tumors will recur, become platinum resistant, and require additional treatment. Platinum resistance is correlated with poor overall survival and reduced therapeutic options for epithelial ovarian cancer (EOC) patients, a leading cause of gynecologic cancer death. Our findings identify a microbial tumor suppressive activity that is disrupted by antibiotics including vancomycin, metronidazole, neomycin, and ampicillin. Starting with a retrospective clinical analysis of OC patients, we found antibiotic use during chemotherapy treatment is associated with poor overall survival. In pre-clinical studies, we found that broad spectrum antibiotics (ABX) therapy, including metronidazole, ampicillin, vancomycin, and neomycin, augments tumor growth of EOC and leads to resistance to cisplatin. In follow up studies we determined vancomycin and metronidazole are sufficient to accelerate ovarian cancer growth and response to cisplatin therapy. Mechanistically, we determined that tumors from ABX treated mice exhibited increased proliferation, reduced apoptosis, decreased DNA damage in cisplatin treated specimens, and increased angiogenesis compared to control treated mice. As these are functional indicators of increased cancer stem cells (CSCs), we analyzed the tumors by RNAseq and single cell spheroid analysis for stem cell frequency. Tumors from ABX treated immune competent mice contained a higher frequency of cisplatin-induced CSCs than tumors from control treated mice. Tumors from untreated mice did not show increased CSCs. We determined that ABX treatment unmasked a microbiome dependent immune suppressor of cancer stem cells as tumors from immune deficient mice exhibited cisplatin induced CSCs in presence or absence of ABX. Finally, we determined that repletion of the microbiome via cecal transplants derived from ABX or control treated mice to recolonize the microbiome of ABX treated mice is sufficient to ameliorate the chemoresistance and survival of ABX treated mice indicative of a gut-derived tumor suppressor. We identified microbial metabolites suppressed in ovarian cancer patients and reduced by ABX in mice as candidate compounds that underlie the tumor suppressive activity. Collectively, the findings indicate the gut microbiome delivers a tumor suppressive signal that is unmasked by ABX treatment. We propose a probiotic strategy as a complement to standard of care may yield improved outcomes in ovarian cancer treatment. Citation Format: Ofer Reizes, Laura Chambers, Chad M. Michener, Mark Brown, Justin D. Lathia, Mohammed Dwidar, Naseer Sangwan, Roberto Vargas, Zeneng Wang, Adeline Hajjar. Gut microbial suppression of epithelial ovarian cancer and attenuation of chemoresistance: opportunity for probiotics in patient care to improve survival [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B090.

Lemierre’s syndrome in pediatric population

Introduction: Lemierre’s syndrome is a rare, potentially fatal complication of upper respiratory tract infections, occurring mainly in young, previously healthy individuals. It is defined as postanginal septicaemia accompanied by thrombosis of the internal jugular vein and formation of abscesses in distant organs. Characteristic symptoms include deterioration of patient’s condition on the 4th–7th day of the management of primary infection, with the recurrence of fever and unilateral swelling and painfulness of the neck. Aims: The analysis of pediatric cases of Lemierre’s syndrome as described in the literature over the last 30 years; presentation of own experience and clinical observations in pediatric patients receiving treatment for Lemierre’s syndrome. Material and methods: A search of the literature available through the PubMed platform was carried out using the query terms “Lemierre syndrome” and “children”. A total of 73 pediatric cases reported on in papers published in English literature within the time span of 1980 through 2023 were included in the analysis. Results: As shown by the analysis of the 73 pediatric cases of Lemierre’s syndrome, the most common causes of the disease were acute pharyngitis and acute otitis media. The presence of the bacterial species Fusobacterium necrophorum was established in the blood cultures of more than one half of the patient group. Distant complications were most frequently observed in the lungs while the most common locations of thrombosis included the internal jugular vein and the sigmoid sinus. Intravenous antibiotic therapy was delivered to all patients, many of whom required additional surgical intervention and/or anticoagulation treatment. Conclusions: In most cases, Lemierre’s syndrome is a complication of acute pharyngitis and acute otitis media. Despite the presence of severe distant organ complications and extensive thrombotic lesions within the venous vessels, complete recovery is achieved in most cases in the pediatric population. The treatment of Lemierre’s syndrome is based primarily on broad-spectrum antibiotic therapy, with surgical interventions and/or anticoagulant therapy being also required in some cases. As of the present, no uniform guidelines have been established for the use of anticoagulant therapy, particularly in the pediatric population.

Immediate vs. culture-initiated antibiotic therapy in suspected non-severe ventilator-associated pneumonia: a before–after study (DELAVAP)

BackgroundVentilator-associated pneumonia (VAP) is the leading nosocomial infection in critical care and is associated with adverse outcomes. When VAP is suspected, starting antibiotic therapy (AT) immediately after pulmonary sampling may expose uninfected patients to unnecessary treatment, whereas waiting for bacteriological confirmation may delay AT in infected patients. As no robust data exist to choose between these strategies, the decision must balance the pre-test diagnostic probability, clinical severity, and risk of antimicrobial resistance. The objective of this study in patients with suspected non-severe VAP was to compare immediate AT started after sampling to conservative AT upon receipt of positive microbiological results. The outcomes were antibiotic sparing, AT suitability, and patient outcomes.MethodsThis single-center, before–after study included consecutive patients who underwent distal respiratory sampling for a first suspected non-severe VAP episode (no shock requiring vasopressor therapy or severe acute respiratory distress syndrome). AT was started immediately after sampling in 2019 and upon culture positivity in 2022 (conservative strategy). The primary outcome was the number of days alive without AT by day 28. The secondary outcomes were mechanical ventilation duration, day-28 mortality, and AT suitability (active necessary AT or spared AT).ResultsThe immediate and conservative strategies were applied in 44 and 43 patients, respectively. Conservative and immediate AT were associated with similar days alive without AT (median [interquartile range], 18.0 [0–21.0] vs. 16.0 [0–20.0], p = 0.50) and without broad-spectrum AT (p = 0.53) by day 28. AT was more often suitable in the conservative group (88.4% vs. 63.6%, p = 0.01), in which 27.9% of patients received no AT at all. No significant differences were found for mechanical ventilation duration (median [95%CI], 9.0 [6–19] vs. 9.0 [6–24] days, p = 0.65) or day-28 mortality (hazard ratio [95%CI], 0.85 [0.4–2.0], p = 0.71).ConclusionIn patients with suspected non-severe VAP, waiting for microbiological confirmation was not associated with antibiotic sparing, compared to immediate AT. This result may be ascribable to low statistical power. AT suitability was better with the conservative strategy. None of the safety outcomes differed between groups. These findings would seem to allow a large, randomized trial comparing immediate and conservative AT strategies.

Anatomical Therapeutic Chemical / Define Daily Dose for evaluation of bronchopneumonia pediatric antibiotics use at Roemani Muhammadiyah Hospital

The increase in repeat hospitalizations after the covid19 pandemic with bronchopneumonia diagnoses in pediatric patients is the first rank. Therapeutic management was associated with the length of hospitalization. Pediatric bronchopneumonia is the case with antibiotic therapy. Current guidelines recommend first-line and alternative options in the management of antibiotic therapy for pneumonia in hospitalized pediatric patients. Empirical broad-spectrum antibiotic therapy for acute infections with consideration of the common etiology of possible pneumococcal involvement The risk of resistance increases with the massive use of antibiotics. The study had an observational descriptive design with retrospective data collection from 280 samples of pediatric patients, aiming to evaluate the use of antibiotics with the ATC/DDD method. Based on empirical selected therapy DDD (Define Daily Dose)/100 patient days, the quantity of antibiotics that are widely used is ceftriaxon 38.36 DDD /100 patient days followed by Cefoperazon sulbactam 3.88 DDD /100 patient days, Cefotaxime 3.77 DDD /100 patient days, Gentamicin 2.57 DDD /100 patient days, Amikacin 1. 70 DDD /100 patient days, Azithromycin 0.76 DDD /100 patient days, Ampicillin Sulbactam 0.50 DDD /100 patient days, Cefixime 0.27 DDD /100 patient days, and Meropenem 0.13 DDD /100 patient days. Drug data included in DU90% are Ceftriaxon, Cefoperzon Sulbactam, Cefotaxime. From the research conducted, the highest DDD/100 patient days value was Ceftriaxon. DDD value indicates high use of antibiotics, does not mean unreasonable use of drugs, so a qualitative review must be done.

The prevalence and clinical context of antimicrobial resistance amongst medical inpatients at a referral hospital in Rwanda: a cohort study

BackgroundAntimicrobial resistance (AMR) is a growing global concern. AMR surveillance is a crucial component of the international response; however, passive surveillance of laboratory data is limited without corresponding patient-level clinical data. This study sought to examine the burden of AMR amongst medical inpatients in Rwanda, in the context of their clinical presentations and prior antibiotic exposures.MethodsThis cohort study was conducted over a 9-month period at a tertiary referral hospital in Kigali, Rwanda. We enrolled 122 adult medical inpatients with a history of fever and a positive microbiological culture result. Data were collected regarding the clinical and microbiological aspects of their admission.ResultsThe most common diagnoses were urinary tract infection (n = 36, 30%), followed by pneumonia (n = 30, 25%) and bacteraemia (11 primary [9%] and 10 catheter-related [8%]). The most common pathogens were E. coli (n = 40, 33%) and Klebsiella pneumoniae (n = 36, 30%). The cohort were heavily antibiotic-exposed at the time of culture with 98% of patients (n = 119) having received an antibiotic prior to culture, with a median exposure of 3 days (IQR 2–4 days). Eighty patients (66%) were specifically prescribed ceftriaxone at the time of culture. Gram-negative organisms predominated (82% [100/122]) and exhibited high rates of resistance, with only 27% (21/77) being susceptible to ceftriaxone, 2.4% (2/82) susceptible to co-amoxiclav and 44% (8/18) susceptible to ciprofloxacin. Susceptibility amongst Gram-negatives was relatively preserved to amikacin (91%, 79/87) and imipenem (85%, 70/82). There were no cases of methicillin-resistant Staphylococcus aureus (0/12) or vancomycin-resistant enterococci (0/2). Discordant antibiotic therapy was significantly associated with in-hospital mortality (OR 6.87, 95%CI 1.80–45.1, p = 0.014).ConclusionsThis cohort highlights high rates of resistance amongst Gram-negative organisms in Rwanda, including the presence of carbapenem resistance. Nonetheless, the detailed prescribing data also highlight the challenges of using routine laboratory data to infer broader AMR prevalence. The significant exposure to empiric broad-spectrum antibiotic therapy prior to culturing introduces a selection bias and risks over-estimating the burden of resistant organisms. Broadening access to microbiological services and active surveillance outside of teaching hospitals are essential to support national and international efforts to curb the growth of AMR in low-resource settings.

Pneumocystis jirovecii pneumonia: a case report

Introduction and importancePneumocystis jirovecii (PJP) pneumonia is a serious life-threatening condition in immunocompromised individuals and is often associated with human immunodeficiency virus (HIV) + patients. We describe a case of PJP pneumonia which provided a diagnostic challenge in a patient who presented with no known risk factors leading to a delay in initiation of appropriate antibiotic therapy.Case presentationA 71-year-old previously healthy white/Caucasian male presented with subacute hypoxic respiratory failure due to multifocal pneumonia with diffuse bilateral ground glass opacities with consolidations despite prior treatment with antibiotics and steroids. He was admitted and started on intravenous broad-spectrum antibiotics but continued to deteriorate, eventually requiring intubation and transfer to the ICU. Bronchoscopy revealed PJP and treatment was initiated, but the patient developed refractory shock and multiorgan failure, and ultimately died. It was later discovered that he was HIV-1 positive.Clinical discussionPJP, as a potential cause of his presentation, was not considered given that our patient lacked any overt risk factors for PJP pneumonia. He continued to worsen despite broad spectrum antibiotic therapy and hence bronchoscopy was pursued. His clinical profile, in hindsight, was suspicious for PJP pneumonia and early PJP-directed antibiotic therapy may have prevented a fatal outcome, as in this case. There was an element of cognitive bias across multiple providers which may have contributed to the delay in treatment despite his rapid clinical decline while on conventional pneumonia treatment protocol. His diagnosis was later evident when his BAL-DFA grew PJP in addition to his low levels of CD4 and CD8 cells. He was found to be HIV-1 positive five days after his death; there was a delay in this diagnosis since all positive HIV tests from the hospital are reported as ‘pending’ until the presumptive positive sample goes to the Connecticut Department of Public Health State laboratory for the confirmatory test. PJP-targeted therapies were initiated later in our patient’s hospital course when the infection had progressed to refractory septic shock with multiorgan failure and eventual death.ConclusionPJP pneumonia is a fatal disease if not recognized early in the course of illness, and the patient usually undergoes multiple antibiotic regimens before they are diagnosed and receive appropriate clinical care. The gold standard of diagnostic testing for PJP is by obtaining bronchial washings through a flexible bronchoscopy and the turnaround time for such results may take a few days to result. A significant proportion of patients may not have any overt risk factors of immunosuppression and early empiric treatment for PJP may be clinically appropriate as the delay in diagnosis may be associated with significant morbidity and mortality risk.

Refractory Osteomyelitis in a Military Service Member Resolved With Adjunctive Hyperbaric Oxygen Therapy.

Refractory osteomyelitis is typically defined as a chronic infection that persists or recurs despite definitive surgical management and antibiotic therapy. Cases often involve complex wounds or fractures and can be challenging to treat, resulting in multiple courses of broad-spectrum antibiotic therapy and numerous surgeries over periods of months to years. Adjuncts to improve resolution of these complicated infections are sorely needed. Here, we describe the case of a 47-year-old active duty military member who sustained an open right ankle fracture during a skydiving accident that was subsequently complicated by refractory osteomyelitis. The patient failed more than three courses of combined medical and surgical management over a 9-month period before undergoing adjunctive hyperbaric oxygen therapy (HBOT), ultimately resulting in resolution of the infection. Adjunctive HBOT for treatment of conditions such as refractory osteomyelitis may be an underutilized resource in part because of a general paucity of high-quality data in the literature supporting its use, as well as a relative lack of availability of this resource. Nonetheless, the overall accumulating body of evidence indicates that the use of adjunctive HBOT in select patients with refractory osteomyelitis is safe and effective and further research may be warranted given its relevance and potential impact to military populations.

High Gastrointestinal Colonization Rate of Vancomycin-Resistant Enterococci among Hospitalized Patients: Potential Source for Resistant Gene.

Vancomycin-resistant Enterococci (VRE) is a global health problem and responsible for healthcare-associated infections (HAIs) in patients with prolonged hospital stay, severe underlying disease, and previous broad-spectrum antibiotic therapy. These bacteria can cross-resist and transfer drug-resistant genes to other potentially pathogenic bacteria. Therefore; this study was aimed to determine the gastrointestinal colonization rate of VRE, its antimicrobial susceptibility profile, and associated factors among hospitalized patients. Prospective cross-sectional study was conducted using stool samples from 223 patients admitted to different wards at Hawassa University Comprehensive Specialized Hospital, from April 1 to June 30, 2021. Patients admitted to the hospital for more than 48 hours for various medical conditions were included. Sociodemographic and clinical characteristics were collected using a structured questionnaire. Fecal specimens were cultured on Enterococci selective media. Enterococcus species were identified using their growth and mannitol fermentation properties. Vancomycin resistance was screened using both the Kirby-Bauer disk diffusion method and a vancomycin E-test strip. Data were entered and analyzed using SPSS version 25. Descriptive and logistic regressions were used to determine the frequency and association of factors with the VRE colonization rate. A p value of <0.05 was considered statistically significant. A total of 223 fecal specimens were collected and processed, and 141 (63.2%) them were positive for Enterococci. The predominant species was E. faecalis 65 (46.1%) followed by E. faecium 76 (53.9%). In this study, the gastrointestinal colonization rate of VRE was 15 (6.7%) and all the species belong to E. faecium. Study participants who had no formal education (AOR = 4.26, 95% CI: 1.01, 18.06), hospitalized patients for >2 weeks (AOR = 4.10, 95% CI: 1.08, 15.57), and those who had a history of treatment with vancomycin (AOR = 4.77, 95% CI: 1.26, 18.09) were more likely to be colonized with vancomycin-resistant Enterococci. More than 95% of Enterococci isolates were susceptible to linezolid, whereas 70.2%, 63.1%, 56.7%, and 53.9% were resistant to tetracycline, erythromycin, penicillin, and ampicillin, respectively. Among the total Enterococci isolated, 141 (54.6%) were multidrug resistant. In our study, high proportion of vancomycin-resistant Enterococci was found. Previous exposure to antibiotics and hospital stay were significant factors for VRE gut colonization. The isolated Enterococci showed variable degrees of resistance to commonly prescribed antibiotics which leads to a worldwide problem multidrug resistance. Therefore, periodic surveillance on antimicrobial resistance pattern, adhering to rational use of antibiotics, and implementing infection prevention protocols may reduce colonization by VRE.

Independent component analysis reveals 49 independently modulated gene sets within the global transcriptional regulatory architecture of multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii causes severe infections in humans, resists multiple antibiotics, and survives in stressful environmental conditions due to modulations of its complex transcriptional regulatory network (TRN). Unfortunately, our global understanding of the TRN in this emerging opportunistic pathogen is limited. Here, we apply independent component analysis, an unsupervised machine learning method, to a compendium of 139 RNA-seq data sets of three multidrug-resistant A. baumannii international clonal complex I strains (AB5075, AYE, and AB0057). This analysis allows us to define 49 independently modulated gene sets, which we call iModulons. Analysis of the identified A. baumannii iModulons reveals validating parallels to previously defined biological operons/regulons and provides a framework for defining unknown regulons. By utilizing the iModulons, we uncover potential mechanisms for a RpoS-independent general stress response, define global stress-virulence trade-offs, and identify conditions that may induce plasmid-borne multidrug resistance. The iModulons provide a model of the TRN that emphasizes the importance of transcriptional regulation of virulence phenotypes in A. baumannii. Furthermore, they suggest the possibility of future interventions to guide gene expression toward diminished pathogenic potential.IMPORTANCEThe rise in hospital outbreaks of multidrug-resistant Acinetobacter baumannii infections underscores the urgent need for alternatives to traditional broad-spectrum antibiotic therapies. The success of A. baumannii as a significant nosocomial pathogen is largely attributed to its ability to resist antibiotics and survive environmental stressors. However, there is limited literature available on the global, complex regulatory circuitry that shapes these phenotypes. Computational tools that can assist in the elucidation of A. baumannii's transcriptional regulatory network architecture can provide much-needed context for a comprehensive understanding of pathogenesis and virulence, as well as for the development of targeted therapies that modulate these pathways.

Normalna ljudska mikrobiota i disbioza - implikacije po zdravlje i bolest

The normal human microbiota, formerly called the "microbial flora," consists of bacteria, fungi, viruses, and parasites that colonise the skin and mucous membranes of the respiratory, gastrointestinal, and genitourinary tracts. The number and diversity of microorganisms varies between different body niches and is greatest in the intestinal tract. The microbiota contributes to the homeostasis of the human organism by preventing colonisation by pathogenic microorganisms, participating in digestive processes and metabolism, and regulating immune functions. Various environmental and genetic factors can lead to an imbalance in the human microbiota, called dysbiosis, which can affect human health. Dysbiosis is usually the result of decreased microbial diversity and a lower number of saprophytic microorganisms, followed by an overgrowth of opportunistic species. The most common diseases directly related to intestinal dysbiosis are antibiotic-associated diarrhoea and pseudomembranous colitis, both of which are associated with the excessive growth of harmful bacteria and Clostridioides difficile following broad-spectrum antibiotic therapy. Dysbiosis is associated with various health conditions or diseases such as acne, psoriasis, eczema, chronic obstructive pulmonary disease, inflammatory bowel disease, obesity, metabolic syndrome, type 2 diabetes, autoimmune diseases and allergies, neurological diseases such as Parkinson's disease, Alzheimer's disease, epilepsy and stroke, depression, anxiety, infertility, preterm birth, and malignancies.

Odontogenic orbital cellulitis: literature review

Introduction: Odontogenic origin is a rare cause (1.3–5%) of cases of orbital cellulitis, but it can lead to very important morbidity such as blindness or thrombosis of the cavernous sinus. It is therefore important to know how to recognize it. Methods: A literature review was performed. The parameters analyzed included age, sex, ethnicity, clinical presentation, imaging to determine orbital involvement, etiology, microbiology, treatment (medical and/or surgical), and final outcome of each case. Chandler's classification was used to classify the different types of cellulitis. Results: Thirty-five cases of odontogenic orbital cellulitis have been described in literature from 1980 to 2022. In 42.9% of cases, the cellulitis corresponded to an intra-orbital abscess (Chandler stage IV). Thrombosis of the cavernous sinus (stage V) was detected in 5.7% of cases. Periorbital edema (100%), ocular or facial pain (82.9%) and limitation of eye movements (82.9%) were the three most common ophthalmological signs. The anamnesis revealed an element pointing to a dental origin in 97.1% of the cases, the two most frequent being a dental avulsion (20%) or an endodontic treatment (14.3%), in days or weeks preceding the onset of symptoms. Imaging was performed on admission in 94.3% of cases. Regarding the most frequently encountered germs, commensal streptococcus of the oral cavity or anaerobic bacteria were found in 25.7% of cases, and coagulase-negative staphylococcus in 22.9% of cases. In 94.3% of cases, broad-spectrum intravenous antibiotic therapy was initiated as soon as the diagnosis was made. The common feature was the use of metronidazole in 51.4% of cases, combined with a third-generation cephalosporin (11.4%) or amoxicillin-clavulanic acid (8.6%). Orbital drainage was necessary in 71.4% of cases to allow resolution of symptoms, associated with drainage of the maxillary sinus in 45.7% of cases. Finally, the treatment allowed a recovery without sequelae in 80% of cases. Discussion: In case of suspected orbital cellulitis, imaging is crucial to confirm the diagnosis, the type of cellulitis and plan the appropriate surgical treatment. The first step of treatment will be the quick start of a broad spectrum intravenous antibiotic therapy, targeting aerobic and anaerobic bacteria. However, it seems imperative to associate a surgical treatment consisting in a first step of an oral drainage and an elimination of the oral infectious source, as well as an orbital drainage whose approach will have been determined by the imaging. Conclusion: Orbital cellulitis is a rare complication of oral cavity infections, but it must be recognized and treated in time to avoid serious morbidity. An early medical and surgical treatment will usually allow good results and a healing process without sequelae.

Accuracy of the GeneXpert® MRSA/SA SSTI test to diagnose methicillin-resistant Staphylococcus spp. infection in bone fixation and fusion and management of infected non-unions

Introduction: The GeneXpert® MRSA/SA SSTI (Methicillin Resistant Staphylococcus aureus / S. aureus skin and soft tissue infection) PCR test allows early detection of methicillin resistance in staphylococci. This test was developed for skin infections and has been evaluated for prosthetic joint infections but, to our knowledge, has not been evaluated for hardware infections outside of arthroplasties. Furthermore, we conducted a retrospective study in patients with non-prosthetic osteosynthesis hardware aiming: 1) to identify the diagnostic values of the PCR test compared to conventional cultures and the resulting rate of appropriate antibiotic therapy. 2) to identify the rate of false negative (FN) results, 3) to identify and compare the rates of failure of infectious treatment (FN versus others) 4) to search for risk factors for FN of the PCR test.Hypothesis: The PCR test allowed early and appropriate targeting of antibiotic therapy.Material and methods: The results of PCR tests and conventional cultures for osteoarticular infections of non-prosthetic hardware over four years (2012-2016) were compared to identify the diagnostic values of using the results of conventional culture as a reference and the rate of appropriate antibiotic therapies. Infectious management failures between the results of the FN group and the others were compared, and variables associated with a FN of the PCR test were identified.Results: The analysis of 419 PCR tests allowed us to establish a sensitivity of 42.86%, a specificity of 96.82%, a positive predictive value of 60% and a negative predictive value of 93.83%. Using the results of the PCR test for the targeting of postoperative antibiotic therapy, it was suitable for staphylococcal coverage in 90.94% (381/419). The rates of patients for whom infectious treatment failed were not significantly different between the FN group and the other patients (20.8% versus 17.7%, respectively; Hazard Ratio = 1.12 (95%CI 0.47-2.69, p = 0.79)). A skin opening during the initial trauma (p = 0.005) and a polymicrobial infection were significantly associated with a risk of FN from the PCR test (p < 0.001).Conclusion: The PCR test makes it possible to reduce the duration of empirical broad-spectrum antibiotic therapy during the treatment of an infection of osteosynthesis hardware but causes a lack of antibiotic coverage in 9.06% of cases.Level of evidence: III; Diagnostic case control study.

Reduced Cytokine Release Syndrome and Improved Outcomes with Earlier Immunosuppressive Therapy in Haploidentical Stem Cell Transplantation

The optimal timing of immunosuppression and post-transplantation cyclophosphamide (PTCy) in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is unknown. However, cytokine release syndrome (CRS) following haplo-HSCT is associated with worse transplantation outcomes, and the incidence of CRS may be affected by the timing of immunosuppression and PTCy. In this study, we compared CRS and other transplantation outcomes in 2 cohorts receiving different immunosuppression and PTCy schedules following haplo-HSCT. This was a retrospective cohort study of 91 patients who underwent haplo-HSCT at the Intermountain Health Blood and Marrow Transplant Program. The original or standard haplo-HSCT GVHD prophylaxis regimen included PTCy on days +3 and +4, with mycophenolate mofetil (MMF) and tacrolimus starting on day +5. The modified regimen adopted in November 2020 changed PTCy to days +3 and +5, with earlier introduction of tacrolimus and MMF, on day -1 and day 0, respectively. Grade ≥1 CRS occurred in 32% of patients in the modified regimen, in 82% of patients in the standard regimen (P <.0001), and 65% overall. Likewise, grade ≥2 CRS was lower with the modified regimen (16% versus 57%; P = .0002). The mean duration of CRS symptoms was longer with the standard regimen (3.14 days versus 1.44 days; P = .0003). The incidence of acute graft-versus-host disease grade III-IV or extensive chronic GVHD (cGVHD) at 1 year was lower in the modified regimen (6% versus 32%; P = .0068). No differences between the standard and modified regimens were seen in overall survival, relapse, or GVHD-free relapse-free survival (GRFS), although there appeared to be a trend toward improved GRFS with the modified regimen. Post hoc analysis comparing GRFS in patients with CRS and those without CRS found that CRS was associated with lower GRFS at 1 year (36% versus 63%; P = .0138). The duration of broad-spectrum antibiotic therapy was decreased by 7.5 days (P = .0017) and the time to hospital discharge was reduced by 7.1 days (P = .0241) with the modified regimen. This is the first analysis to evaluate and find a difference in CRS with early initiation of immunosuppressive therapy in haplo-HSCT. Our results suggest that this modified GVHD regimen benefits patients by reducing CRS and high-grade GVHD compared to the standard PTCy-based GVHD prophylaxis regimen in haplo-HSCT. Additionally, this novel regimen did not appear to negatively impact outcomes.