Broad-spectrum Antimicrobial Therapy Research Articles

A General Strategy for Enhanced Photodynamic Antimicrobial Therapy with Perylenequinonoid Photosensitizers Using a Macrocyclic Supramolecular Carrier.

Perylenequinonoid natural products are a class of photosensitizers (PSs) that exhibit high reactive oxygen species (ROS) generation and excellent activity for Type I/Type II dual photodynamic therapy. However, their limited activity against gram-negative bacteria and poor water solubility significantly restrict their potential in broad-spectrum photodynamic antimicrobial therapy (PDAT). Herein, a general approach to overcome the limitations of perylenequinonoid photosensitizers (PQPSs) in PDAT by utilizing a macrocyclic supramolecular carrier is presented. Specifically, AnBox·4Cl, a water-soluble cationic cyclophane, is identified as a universal macrocyclic host for PQPSs such as elsinochrome C, hypocrellin A, hypocrellin B, and hypericin, forming 1:1 host-guest complexes with high binding constants (≈107 m -1) in aqueous solutions. Each AnBox·4Cl molecule carries four positive charges that promote strong binding with the membrane of gram-negative bacteria. As a result, the AnBox·4Cl-PQPS complexes can effectively anchor on the surfaces of gram-negative bacteria, while the PQPSs alone cannot. In vitro and in vivo experiments demonstrate that these supramolecular PSs have excellent water solubility and high ROS generation, with broad-spectrum PDAT effect against both gram-negative and gram-positive bacteria. This work paves a new path to enhance PDAT by showcasing an efficient approach to improve PQPSs' water solubility and killing efficacy for gram-negative bacteria.

Polymicrobial brain abscesses: A complex condition with diagnostic and therapeutic challenges.

Brain abscesses (BA) are focal parenchymal infections that remain life-threatening conditions. Polymicrobial BAs (PBAs) are complex coinfections of bacteria or bacterial and nonbacterial pathogens such as fungi or parasites, with diagnostic and therapeutic challenges. In this article, we comprehensively review the prevalence, pathogenesis, clinical manifestations, and microbiological, histopathological, and radiological features of PBAs, as well as treatment and prognosis. While PBAs and monomicrobial BAs have some similarities such as nonspecific clinical presentations, PBAs are more complex in their pathogenesis, pathological, and imaging presentations. The diagnostic challenges of PBAs include nonspecific imaging features at early stages and difficulties in identification of some pathogens by routine techniques without the use of molecular analysis. Imaging of late-stage PBAs demonstrates increased heterogeneity within lesions, which corresponds to variable histopathological features depending on the dominant pathogen-induced changes in different areas. This heterogeneity is particularly marked in cases of coinfections with nonbacterial pathogens such as Toxoplasma gondii. Therapeutic challenges in the management of PBAs include initial medical therapy for possibly underrecognized coinfections prior to identification of multiple pathogens and subsequent broad-spectrum antimicrobial therapy to eradicate identified pathogens. PBAs deserve more awareness to facilitate prompt and appropriate treatment.

The Importance of Nonpharmacological Applications in the Management of Infections Caused by Stenotrophomonas maltophilia in Pediatric Patients: A Single-Center Experience

Abstract Objective This study aimed to contribute to the literature by evaluating the clinical characteristics of children with Stenotrophomonas maltophilia infection, predisposing factors, and implementation of additional measures for disease control, with the goal of improving survival and reducing mortality in pediatric patients. Methods Clinical data and microbiological test results of patients with S. maltophilia growth in cultures of samples from any biological site and clinical symptoms of systemic infection referred to the pediatric clinic of a tertiary university hospital between January 2021 and August 2023 were reviewed. Results The study included 40 patients with a median age of 2.5 years (range 1–16 years). Medical devices were present in 26 patients (65%). Polymicrobial growth occurred in 16 patients (40%). Prior to the detection of S. maltophilia infection, 35 patients (87.5%) received broad-spectrum antimicrobial therapy. Death occurred in 11 patients (27.5%). In 2022, there were 23 cases of S. maltophilia infection, with the highest number occurring in March 2022 (9 cases per month). After that date, various nonpharmacological measures were implemented for all patients with confirmed infection, including strict contact isolation in single-occupancy, high-efficiency particulate air-filtered rooms. Conclusion There were multiple risk factors for increased mortality in our study population. Despite these unfavorable factors, the mortality rate was low. Disease control was achieved through nonpharmacological interventions implemented alongside antimicrobial therapy, resulting in effective prevention of potential outbreaks. Implementation of nonpharmacological interventions alongside medical treatment can reduce mortality and improve survival in pediatric patients with S. maltophilia infection.

A multifunctional guanosine-based carbon dots for dead microbial imaging and synergistic broad-spectrum antimicrobial therapy

Pathogenic microbial infection poses serious threats to human lives and antibiotic abuse leads to bacterial resistance. The development of alternative antibacterial agents and strategies with reduced resistance risk is urgently demanded. Heteroatom doping is a feasible method for adjusting the electronic and optical properties of carbon dots (CDs) to improve their bioimaging performance and light-mediated therapeutic efficiency. Herein, we synthesized a series of guanosine-derived CDs from guanosine (G), guanosine monophosphate (GMP), guanosine diphosphate (GDP), and guanosine triphosphate (GTP) as respective precursors. G-CDs, prepared by guanosine with strong surface negative charge and suitable size, can successfully differentiate and stain dead microbial cells (bacteria and fungi). G-CDs with a high N content exhibited the highest antibacterial activity in vitro and in vivo among the four guanosine-derived CDs, owing to triple synergistic antibacterial actions - the intrinsic antibacterial mechanism, bacterial photodynamic and photothermal inactivation against bacteria and fungi. In this paper, we present a promising new method to prepare CDs using natural biomolecules from living systems as precursors for multifunctional dead microbial cells imaging and broad-spectrum theranostic applications.

Ventilation Management in a Patient with Ventilation–Perfusion Mismatch in the Early Phase of Lung Injury and during the Recovery

Chest trauma is one of the most serious and difficult injuries, with various complications that can lead to ventilation–perfusion (V/Q) mismatch and systemic hypoxia. We are presenting a case of a 53-year-old male with no chronic therapy who was admitted to the Intensive Care Unit due to severe respiratory failure after chest trauma. He developed a right-sided pneumothorax, and then a thoracic drain was placed. On admission, the patient was hemodynamically unstable and tachypneic. He was intubated and mechanically ventilated, febrile (38.9 °C) and unconscious. A lung CT showed massive non-ventilated areas, predominantly in the right lung, guiding repeated therapeutic and diagnostic bronchoalveolar lavages. He was ventilated with PEEP of 10 cmH2O with a FiO2 of 0.6–0.8. Empirical broad-spectrum antimicrobial therapy was immediately initiated. Both high FiO2 and moderate PEEP were maintained and adjusted according to the current blood gas values and oxygen saturation. He was weaned from mechanical ventilation, and non-invasive oxygenation was continued. After Stenotrophomonas maltophilia was identified and treated with sulfamethoxazole/trimethoprim, a regression of lung infiltrates was observed. In conclusion, both ventilatory and antibiotic therapy were needed to improve the oxygenation and outcome of the patient with S. maltophilia pneumonia and V/Q mismatch.

Pediatric Sepsis Diagnosis, Management, and Sub-phenotypes.

Sepsis and septic shock are major causes of morbidity, mortality, and health care costs for children worldwide, including >3 million deaths annually and, among survivors, risk for new or worsening functional impairments, including reduced quality of life, new respiratory, nutritional, or technological assistance, and recurrent severe infections. Advances in understanding sepsis pathophysiology highlight a need to update the definition and diagnostic criteria for pediatric sepsis and septic shock, whereas new data support an increasing role for automated screening algorithms and biomarker combinations to assist earlier recognition. Once sepsis or septic shock is suspected, attention to prompt initiation of broad-spectrum empiric antimicrobial therapy, fluid resuscitation, and vasoactive medications remain key components to initial management with several new and ongoing studies offering new insights into how to optimize this approach. Ultimately, a key goal is for screening to encompass as many children as possible at risk for sepsis and trigger early treatment without increasing unnecessary broad-spectrum antibiotics and preventable hospitalizations. Although the role for adjunctive treatment with corticosteroids and other metabolic therapies remains incompletely defined, ongoing studies will soon offer updated guidance for optimal use. Finally, we are increasingly moving toward an era in which precision therapeutics will bring novel strategies to improve outcomes, especially for the subset of children with sepsis-induced multiple organ dysfunction syndrome and sepsis subphenotypes for whom antibiotics, fluid, vasoactive medications, and supportive care remain insufficient.

Analysis of Blood Cultures of Patients Presenting to the Emergency Department in a Tertiary Healthcare Hospital in Mumbai

Aim and objectives: Analysis of blood cultures taken from patients attending emergency departments is an important exercise in determining the common pathogens prevalent in the region. The distribution of these infective pathogens keeps changing over time, and the rise in antimicrobial-resistant pathogens makes it difficult to routinely conduct effective empirical broad-spectrum antimicrobial therapy. This study aimed to analyse the results of blood cultures obtained from patients presenting to the Emergency Department of a Tertiary Healthcare Hospital in Mumbai and provide updated and detailed information on the distribution of causative pathogens in adult sepsis and study their antibiotic-susceptibility pattern. Materials and methods: A hospital-based prospective cross-sectional study of 121 positive blood culture reports was conducted at the Department of Emergency Medicine, Fortis Hospital Mulund, Mumbai, which included all adult (age > 18 yrs) suspected sepsis patients arriving to the Emergency Department whose blood cultures were sent from the Emergency Department from January 2021 to December 2021. Results: The study showed that mean age of the study cases was 59.3 years with 59.5% cases that belonged to the elderly age group with a male predominance (56.2% males–43.8% females). Overall, Gram-negative isolates were seen in 95% cases, while Gram-positive isolates were seen in only 1.7% cases. The most common organism isolated from cases with sepsis was Escherichia coli (45.5%) followed by Klebsiella (13.2%), Salmonella (10.7%), Stenotrophomonas (7.4%) and Pseudomonas (5%). Among Gram-positive organisms, Staphylococcus aureus was the most common organism isolated (1.7%). Escherichia coli isolates showed poor sensitivity towards fluoroquinolones and cephalosporins while good sensitivity towards aminoglycosides, carbapenems and combination drugs like Cefoperazone and Sulbactam and Piperacillin and Tazobactam. These findings suggest that Gram-negative organisms are the most common isolates observed in this study, with E. coli being the predominant pathogen followed by Klebsiella. High-level antimicrobial resistance was observed in sepsis cases for commonly used antimicrobials like fluoroquinolones and cephalosporins.

Spontaneous necrotizing soft-tissue infections in patient with diabetes: Case report

Necrotizing skin and soft-tissue infections (NSTI) are rare but potentially life-threatening and disabling infections that often require intensive care unit admission. The initial presentation of a patient with NSTI can be misleading, as features of severe systemic toxicity can obscure sometimes less impressive skin findings. The infection can spread rapidly, and delayed surgery worsens the prognosis; hence, there is a limited role for additional imaging in critically ill patients. In addition, the utility of clinical scores is contested. Prompt surgery with aggressive debridement of necrotic tissue is required for source control and allows for microbiological sampling. Moreover, prompt administration of broad-spectrum antimicrobial therapy is warranted, with the addition of clindamycin for its effect on toxin production, both in empirical therapy and in targeted therapy for monomicrobial group A streptococcal and clostridial NSTI.

Emphysematous Hepatitis: A Rare Cause of Septic Shock

Emphysematous hepatitis is a rare fatal, rapidly progressive infection of the liver that typically occurs in individuals with diabetes. It is characterized by the accumulation of gas in the hepatic parenchyma replacing the healthy tissue and leading to acute liver failure. In this study, we present a case of emphysematous hepatitis affecting a 54-year- old diabetic man with extensive segmental replacement of liver parenchyma by gas. Although the patient received early broad-spectrum antimicrobial therapy and supportive care, the condition progressed to a fatal outcome, which is consistent with other case reports. It is crucial for radiologists and clinicians to be aware of this condition and its potential fatality, allowing for early diagnosis and aggressive management to improve patient outcomes.

Concentrations of penicillin and gentamicin following intrauterine administration of two compounded formulations

The use of broad-spectrum antimicrobial therapy either by intrauterine or systemic route is commonplace in equine practice, however, much remains unknown about antibiotic efficacy in this environment. We recently demonstrated the activity of penicillin and gentamicin against common endometrial pathogens ex vivo.1 The objective of this study was to measure the concentration of gentamicin and penicillin in the uterine fluid of mares following intrauterine infusion of either a standard (PPGent) or long-acting (LA-PPGent) compounded formulation of procaine penicillin and gentamicin. We hypothesized that both drug formulations would result in therapeutic concentrations following administration, with total concentrations sustained for longer using the long-acting formulation (LA-PPGent). Ten reproductively sound mares in early estrus were administered 2378mg of procaine penicillin and 200mg of gentamicin via a single intrauterine infusion in either a standard (n=5) or a lyophilized formulation suspended in a slow-release matrix (n=5). Intrauterine fluid was collected at 0.5, 2, 4, 8, 24, 32, 48 and 72 h following infusion. A pre-weighed section of umbilical tape was introduced into the uterus through a double-guarded pipette for 30 seconds and then weighed to determine the absorbed fluid volume. Penicillin and gentamicin analyses were performed using high-performance liquid chromatography(HPLC) and ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS), respectively. Penicillin and gentamicin concentrations were assessed between groups and over time using a repeated measures analysis with treatment, time, and their interaction in the model statement with significance set at p<0.05. Mean intrauterine drug concentrations of PPGent peaked at 0.5 hours (Penicillin: 10,123.0 ± 4,298.0 µg/mL, Gentamicin: 3,397.3 ± 1,338.5 µg/mL), well above concentrations previously shown to inhibit bacterial growth ex vivo ([1] Von Dollen et al. J Equine Vet Sci 2019;79:121-26), and exceeded MIC for relevant organisms for 72 hours (Penicillin: 2.59 ± 6.34 µg/mL, Gentamicin: 2.14 ± 2.4 µg/mL). Mean concentrations of LA-PPG were lower at peak (Penicillin: 2,213.8 ± 967.8 µg/mL – p<0.05, Gentamicin: 1,859 ± 2,413 µg/mL) and exceeded MIC for 24h and 32h, respectively. These results support the use of procaine penicillin and gentamicin as intrauterine antimicrobial therapeutics. The long-acting formulation was not found to extend the time over MIC of antibiotics in the uterus of estrus mares. Acknowledgements: LA-PPGent was prepared by SR Veterinary Technologies LLC, Windsor CO using previously lyophilized PPGent. This research was supported by the Grayson-Jockey Club Research Foundation.

Nanopore-Based Metagenomic Sequencing in Respiratory Tract Infection: A Developing Diagnostic Platform.

Respiratory tract infection (RTI) remains a significant cause of morbidity and mortality across the globe. The optimal management of RTI relies upon timely pathogen identification via evaluation of respiratory samples, a process which utilises traditional culture-based methods to identify offending microorganisms. This process can be slow and often prolongs the use of broad-spectrum antimicrobial therapy, whilst also delaying the introduction of targeted therapy as a result. Nanopore sequencing (NPS) of respiratory samples has recently emerged as a potential diagnostic tool in RTI. NPS can identify pathogens and antimicrobial resistance profiles with greater speed and efficiency than traditional sputum culture-based methods. Increased speed to pathogen identification can improve antimicrobial stewardship by reducing the use of broad-spectrum antibiotic therapy, as well as improving overall clinical outcomes. This new technology is becoming more affordable and accessible, with some NPS platforms requiring minimal sample preparation and laboratory infrastructure. However, questions regarding clinical utility and how best to implement NPS technology within RTI diagnostic pathways remain unanswered. In this review, we introduce NPS as a technology and as a diagnostic tool in RTI in various settings, before discussing the advantages and limitations of NPS, and finally what the future might hold for NPS platforms in RTI diagnostics.

A Rapidly Fatal Case of Anti-GFAP Receptor Encephalitis Due to Acute Brain Edema and Herniation

Objective Glial fibrillary acidic protein antibody (GFAP) is a newly recognized biomarker for an immunotherapy responsive autoimmune meningo-encephalomyelitis with a wide variety of clinical presentations. We report the second GFAP antibody positive case in a young man who died despite appropriate and aggressive immunomodulatory treatment. Background 29 year old previously healthy male with childhood immune disorder presented with 3 week history of acute progressive worsening headaches, bloody emesis, nausea, blurry vision and generalized weakness. Exam was significant for downbeating nystagmus, limb ataxia and tremor and later progressing into inattention, confusion, urinary retention, asymmetric pupils, hyprreflexia and lack of motor or sensory response. Lumbar puncture revealed lymphocytic pleocytosis with elevated protein and opening pressure of 36 cm H20. MRI demonstrated areas of restricted diffusions symmetrically involving white matter of the corpus callosum, middle cerebellar peduncle, cerebellar white matter bilaterally as well as within the pons centrally. Patient was started on intravenous immunogammaglobulin (IVIG) and pulse corticosteroids along with broad spectrum antimicrobial therapy. After an initial apparent response to treatment, repeat head CT showed Diffuse Sulci effacement. Shortly after, He rapidly decompensated with clinical findings indicating brainstem herniation, cardiac arrest and brain death was diagnosed. CSF studies subsequently were reported as positive for GFAP antibodies. An autopsy reported the cause of death as cerebellar tonsillar herniation secondary to diffuse cerebral edema. all sections showed perivascular inflammation and gliosis. Design/Methods NA. Results NA. Conclusions This reported case of anti-GFAP meningo-encephalomyelitis is unusual for the rapid onset of cerebral edema and rapid progression to herniation and brain death occurring only 4 weeks after symptom onset. While this may be a rare complication of Anti GFAP encephalitis, clinicians should be vigilant for acutely increased intracranial pressure in patients with clinical findings of encephalitis in general.

Septic Pulmonary Embolism: A Contemporary Profile.

Septic pulmonary embolism (SPE) is a rare clinical entity that is distinct from the classic and more common non-septic thrombotic pulmonary embolism. SPE should be suspected in patients with a systemic acute inflammatory reaction or sepsis who develop signs and symptoms of pulmonary involvement. The diagnosis of SPE depends on the specific radiologic finding of multiple, peripheral, nodular, possibly cavitated lesions. SPE should prompt an immediate search for the primary source of infection; typically, right-sided infective endocarditis, cardiac implantable electronic devices, and septic thrombophlebitis as a complication of bone, skin, and soft tissue infection including Lemierre's syndrome, indwelling catheters, or direct inoculation via injection drug use. Invasive treatment of the infection source may be necessary; in thrombophlebitis, the efficacy and safety of anticoagulation remain undefined. Blood cultures may be negative, particularly among patients with recent antibiotic exposure, and broad-spectrum antimicrobial therapy should be considered. The in-hospital mortality of SPE ranges up to 20% in published case series. While trends in the incidence of SPE are unknown, the opioid epidemic, the growing use of cardiac implantable electronic devices worldwide, and the reported increase in cases of septic thrombophlebitis may be leading to an escalation in SPE cases. We provide a contemporary profile of SPE and propose a clinical management algorithm in patients with suspected or confirmed SPE.

Antimicrobial therapy of community-acquired pneumonia during stewardship efforts and a coronavirus pandemic: an observational study

BackgroundCommunity-acquired pneumonia (CAP) is the most frequent infection diagnosis in hospitals. Antimicrobial therapy for CAP is depicted in clinical practice guidelines, but adherence data and effect of antibiotic stewardship measures are lacking.MethodsA dedicated antibiotic team pointed out CAP as a potential target for antimicrobial stewardship (AMS) measures at a 1.000-bed, tertiary care, teaching university hospital in Norway from March until May for the years 2016 throughout 2021. The aim of the AMS program was to increase diagnostic and antimicrobial therapy adherence to national clinical practice guideline recommendations through multiple and continuous AMS efforts. Descriptive statistics were retrospectively used to delineate antimicrobial therapy for CAP. The primary outcomes were proportions that received narrow-spectrum beta-lactams, and broad-spectrum antimicrobial therapy.Results1.112 CAP episodes were identified. The annual proportion that received narrow-spectrum beta-lactams increased from 56.1 to 74.4% (p = 0.045). Correspondingly, the annual proportion that received broad-spectrum antimicrobial therapy decreased from 34.1 to 17.1% (p = 0.002). Trends were affected by the coronavirus pandemic. Mortality and 30-day readmission rates remained unchanged. De-escalation strategies were frequently unutilized, and overall therapy duration exceeded clinical practice guideline recommendations substantially. Microbiologically confirmed CAP episodes increased from 33.7 to 56.2% during the study period.ConclusionCAP is a suitable model condition that is sensitive to AMS measures. A continuous focus on improved microbiological diagnostics and antimicrobial therapy initiation is efficient in increasing adherence to guideline recommendations. There is an unmet need for better antimicrobial de-escalation strategies.

BACTERIAL TRACHEITIS IN A PATIENT AFTER INTUBATION

BACTERIAL TRACHEITIS IN A PATIENT AFTER INTUBATION

Use of broad-spectrum antimicrobials for more than 72 h and the detection of multidrug-resistant bacteria in Japanese intensive care units: a multicenter retrospective cohort study

BackgroundLarge multicenter studies reporting on the association between the duration of broad-spectrum antimicrobial administration and the detection of multidrug-resistant (MDR) bacteria in the intensive care unit (ICU) are scarce. We evaluated the impact of broad-spectrum antimicrobial therapy for more than 72 h on the detection of MDR bacteria using the data from Japanese patients enrolled in the DIANA study.MethodsWe analyzed the data of ICU patients in the DIANA study (a multicenter international observational cohort study from Japan). Patients who received empirical antimicrobials were divided into a broad-spectrum antimicrobial group and a narrow-spectrum antimicrobial group, based on whether they received broad-spectrum antimicrobials for more or less than 72 h, respectively. Differences in patient characteristics, background of infectious diseases and empirical antimicrobial administration, and outcomes between the two groups were compared using the chi-square tests (Monte Carlo method) for categorical variables and the Mann–Whitney U-test for continuous variables. We also conducted a logistic regression analysis to investigate the factors associated with the detection of new MDR bacteria.ResultsA total of 254 patients from 31 Japanese ICUs were included in the analysis, of whom 159 (62.6%) were included in the broad-spectrum antimicrobial group and 95 (37.4%) were included in the narrow-spectrum antimicrobial group. The detection of new MDR bacteria was significantly higher in the broad-spectrum antimicrobial group (11.9% vs. 4.2%, p = 0.042). Logistic regression showed that broad-spectrum antimicrobial continuation for more than 72 h (OR [odds ratio] 3.09, p = 0.047) and cerebrovascular comorbidity on ICU admission (OR 2.91, p = 0.041) were associated with the detection of new MDR bacteria.ConclusionsAmong Japanese ICU patients treated with empirical antimicrobials, broad-spectrum antimicrobial usage for more than 72 h was associated with the increased detection of new MDR bacteria. Antimicrobial stewardship programs in ICUs should discourage the prolonged use of empirical broad-spectrum antimicrobial therapy.Trial registration ClinicalTrials.gov, NCT02920463, Registered 30 September 2016, https://clinicaltrials.gov/ct2/show/NCT02920463

P215 Investigation of an outbreak of neonatal Candida emia in the NICU of a 300 -bedded hospital in North India

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectivesNeonatal Candidaemia causes significant morbidity and mortality in very low birth weight neonates. We report the occurrence of an outbreak of neonatal Candidaemia due to Candida krusei in the neonatal intensive care unit (NICU) of a 300-bedded hospital in North India.MethodsA total of 96 blood cultures from 80 neonates admitted in the NICU from October 2020 to April 2021 were received and processed manually in the Microbiology lab. A total of 5 among the 47 yeast isolates were sent to a teaching hospital for identification and antifungal susceptibility testing by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF). Clinical parameters (very low birth weight, gestational age, birth asphyxia, broad-spectrum antimicrobial therapy, intra-uterine growth restriction, and total parenteral nutrition), lab parameters (CRP, platelet count), and patient outcome were evaluated. A total of 26 environmental samples and hand swabs from six health care workers were collected to trace the source of the outbreak. The samples were inoculated on 5% sheep blood agar and MacConkey agar. Regular rounds of the NICU and training sessions were conducted by the infection control team to intensify the infection control measures.ResultsBlood culture results: In all, 57 neonates (71.25%; 57/80) admitted to the NICU had positive blood cultures. A total of 47 blood cultures yielded non-albicans Candida spp. (82.45%; 47/57). The other microorganisms isolated from blood cultures were Pseudomonas aeruginosa (4), MRSA (3), Klebsiella pneumoniae (4) and Acinetobacter baumanni (1). Polymicrobial bloodstream infections were detected in two neonates. All the yeast isolates subjected to MALDI-TOF were identified as Candida krusei and had similar MICs of 0.25, 4, 16, 1, 0.25 and 16 μg/ml for voriconazole, itraconazole, posaconazole, caspofungin, micafungin and fluconazole respectively.Culture results of environmental sampling: Yeast could not be isolated from any environmental sample and hand swabs of health care workers. However, MRSA was isolated from the hands of one health care worker.Observation during the infection control rounds:Sterile gauze pieces soaked in iodine and kept in plastic bottles were being used for skin antisepsis before collecting samples or before introducing an IV cannula.The nursing staff did not wear sterile gloves while collecting blood samples or introducing IV cannula in case of NICU patients.It was observed that the used bottles of IV fluids (eg. Ringer lactate, normal saline) were not capped and kept at room temperature.Intensive infection control measures and training sessions were effective in controlling the outbreak.ConclusionWe report the occurrence of a massive outbreak of neonatal Candidaemia in the NICU of our hospital with a positivity rate of 58.75% (47/80). Identification of yeast and determination of antifungal susceptibility is important for prompt treatment. Though the source of the outbreak could not be traced but intensifying infection control practices could control the outbreak. This study emphasizes the value of educating healthcare workers and regular monitoring of disinfection practices to prevent health-care-associated infections.

Safety of De-Escalating Empiric Antimicrobial Agents in Trauma Patients with Indigenous Oral Flora Ventilator-Associated Pneumonia.

Background: Ventilator-associated pneumonia (VAP) is a frequently occurring nosocomial infection in critically ill trauma patients. When bronchoalveolar lavage (BAL) returns with indigenous oral flora (IOF), de-escalating antimicrobial therapy is challenging. Patients and Methods: This is a retrospective review of trauma patients who received broad-spectrum empiric antimicrobial therapy for clinical VAP, and whose BAL culture resulted with >100,000 CFU/mL of IOF from September 1, 2017 to September 1, 2020. Patients were identified using the trauma database and microbiology reports of BALs with IOF. This review evaluated the effect of antibiotic de-escalation on recurrent or persistent pneumonia. Results: Of 51 trauma patients with clinical VAP and IOF, 18 patients (35.3%) had antimicrobial agents de-escalated. De-escalation was driven primarily by the discontinuation of vancomycin, with the continuation of a β-lactam antibiotic as monotherapy for the remainder of the treatment course (n = 15; 86.7%). The overall rate of either persistent or recurrent VAP in the cohort was 10%, and this did not differ statistically between those who received de-escalation therapy after isolation of IOF and those who did not (16.7% vs. 6.1%; p = 0.224), however, the incidence of acute kidney injury (AKI) was higher in the non-de-escalation group (39.4% vs. 11.1%; p = 0.034). There was no statistical difference in ventilator days, intensive care unit (ICU) length of stay, or hospital length of stay between treatment groups. Conclusions: Trauma patients who develop VAP with isolated BAL cultures of IOF or mixed flora can safely have anti-methicilllin-resistant Staphylococcus aureus (MRSA) antimicrobial agents discontinued, and this may result in decreased rates of AKI.

Microbiological analysis of peritoneal fluid samples from patients with perforated peptic ulcer – retrospective observational study

Peritonitis due to perforated peptic ulcer (PPU) is a surgical emergency associated with high mortality. Preoperative management includes immediate initiation of broad-spectrum antimicrobial therapy. The objective of this study was to assess the spectrum of microbial pathogens in peritoneal fluid. Retrospective observational study of patients who underwent surgery for PPU at the 1st Department of Surgery - Thoracic, Abdominal and Injury Surgery, General University Hospital in the period 2015-2020. Analysis of the microbiological analytical results of peritoneal fluid. The microbiological profile of PPU-associated peritonitis is somewhat different from microbial pathogens involved in secondary peritonitis due to bowel perforation. A high rate of negative culture findings, high incidence of Candida spp. and low incidence of anaerobic bacteria are characteristic for PPU-associated peritonitis. Negative culture from the peritoneal fluid collected during surgery was identified in 42% of the patients. A total of 66 isolates of microbial pathogens were identified, including Candida spp. (42.5%), aerobic gram-positive bacteria (30.3%), aerobic gram-negative bacteria (22.7%) and anaerobic bacteria (4.5%). Candida albicans and Candida glabrata represented the most common species. Decreased susceptibility to fluconazole and resistance to itraconazole was associated with all Candida glabrata isolates. Although PPU-associated peritonitis is mostly of community origin, we confirmed a significant incidence of Candida spp. with decreased azole susceptibility. The choice of antifungal therapy should always be based on local epidemiology.

Potential Impact of Rapid Multiplex PCR on Antimicrobial Therapy Guidance for Ventilated Hospital-Acquired Pneumonia in Critically Ill Patients, A Prospective Observational Clinical and Economic Study.

ObjectivesTo investigate the potential impact of the syndromic multiplex FilmArray® Pneumonia plus Panel (FAPP) on the antimicrobial treatment guidance of patients with ventilated hospital-acquired pneumonia (VHAP).MethodsRespiratory fluids from 100 adult patients with VHAP, receiving invasive mechanical ventilation in three intensive care units from one French university hospital, were tested prospectively using FAPP. Conventional cultures were performed in parallel as routine practice. Clinicians were left blinded to the FAPP results. Antimicrobial therapies based on FAPP results were simulated by independent blinded experts according to a predefined algorithm and compared to 1) those prescribed in practice according to local guidelines (real-life), and 2) those that complied with the international ERS/ESICM/ESCMID/ALAT recommendations. The primary endpoint was the number of days of broad-spectrum antimicrobial therapy. Secondary endpoints were the rates of microbiological treatment failure and cost-effectiveness ratio.ResultsThe predicted median duration of broad-spectrum antibiotics was 0 [0-1.25] day in the FAPP-based simulation, versus 2 [0-6] days in real-life (p<0.0001) and 2 [2-3.25] days in the recommendations-based simulation (p<0.0001). Treatment failure was predicted in 3% of cases with FAPP results versus observed in 11% in real-life (p=0.08) and 6% with recommendations-based simulation (p=0.37). The incremental cost-effectiveness ratio was 1 121 € [-7021; 6794] to avoid one day of non-optimized antimicrobial therapy.ConclusionsOur results suggest that using FAPP in patients with VHAP has the potential to reduce the use of broad-spectrum antimicrobial therapy without increasing the risk of microbial treatment failure.