Empiric Antimicrobial Regimens Research Articles

Empiric antibiotic prescribing practices for gram-positive coverage of late-onset sepsis in neonatal intensive care units in North America.

Late-onset sepsis (LOS) in the neonatal intensive care unit (NICU) causes significant morbidity and mortality, yet guidance on empiric management is limited. We surveyed NICUs across Canada and the United States regarding their empiric antimicrobial regimens for LOS, thereby identifying large practice variations and high rates of empiric vancomycin use.

Efficacy of empirical Ciprofloxacin or Cefixime plus Metronidazole therapy for the treatment of liver abscess: a randomized control clinical trial

Liver abscess is a potentially life-threatening medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage is therapeutic. The rational for using empirical intravenous broad-spectrum antimicrobials upfront instead of oral Fluoroquinolone or Cephalosporin is contentious. In this double blind randomized control clinical trial 69 participants received Ciprofloxacin (500 mg q 12 hourly) and 71 participants received Cefixime (200 mg q 12 hourly) orally for 2 weeks. Both the group received oral Metronidazole (800 mg q 8 hourly) for 2 weeks and percutaneous drainage or aspiration of the abscess was done as per indication and followed-up for 8 weeks. Out of 140 participants, 89.3% (N = 125) achieved clinical cure, 59 (85.5%) in Ciprofloxacin group and 66 (93%) in Cefixime group (p = 0.154). Mean duration of antimicrobial therapy was 16.2 ± 4.3 days, 15.1 ± 4.5 days in Ciprofloxacin group and 16.0 ± 4.2 days in Cefixime group (p = 0.223). Total 15 (10.7%) participants had treatment failure, 10 (14.5%) in Ciprofloxacin group and 5 (7.0%) in Cefixime group (p = 0.154). The most common reason for treatment failure was need of prolong (> 4 weeks) antimicrobial therapy due to persistent hepatic collection requiring drainage, which was significantly (p = 0.036) higher in Ciprofloxacin (14.5%, N = 10) group, compared to the Cefixime (4.2%, N = 3) group. In conclusion, both, the Ciprofloxacin or Cefixime plus Metronidazole for duration of 2–3 weeks were efficacious as empirical oral antimicrobial regimen along with prompt percutaneous drainage or aspiration for the treatment of uncomplicated liver abscess with similar efficacy. Oral Cefixime was better than Ciprofloxacin in term of lesser chance of treatment failure due to persistent collection which is required to be investigated further in larger clinical trial.Trial registration: clinicaltrials.gov PRS ID: NCT03969758, 31/05/2019.

PREVALENCE OF FLUOROQUINOLONES RESISTANCE AMONG ESBL-PRODUCING ESCHERICHIA COLI ISOLATED FROM URINE SAMPLES

BACKGROUND
 Resistance among uropathogens has emerged as a growing concern necessitating re-evaluation of the efficacy of recommended empiric antimicrobial regimens. Misuse and overuse of various antibacterial agents in hospitals is a key cause of the emergence of anti-microbial resistance.
 Aims: To identify the prevalence of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli from urine specimens and to know the prevalence of Fluoroquinolone resistance among ESBL-producing Escherichia coli (E. coli) isolates.
 Material and method: The study was conducted on 500 E. coli isolates from urine samples received in the Department of Microbiology, MMIMSR, Mullana, Ambala. The organism isolation and identification were done as per the standard procedures and antibiotic sensitivity testing was done following CLSI guidelines. All the strains were screened out for ESBL production as per CLSI guidelines. Ciprofloxacin, Norfloxacin, and Ofloxacin discs were used for the detection of fluoroquinolone resistance.
 Results: Out of the total 500 E. Coli isolates from urine samples received in our laboratory, 69% were found to be ESBL producers.
 Conclusion: We found a high level of quinolone resistance among ESBL-producing Escherichia coli strains isolated from patients with UTI. Because of the widespread use of fluoroquinolones in our country, there is a need for sensitive antibiotic stewardship. Further research is needed to ascertain the gravity of quinolone resistance and to swiftly act against its spread among other nosocomial pathogens.

The Microbiological Profile and Antibiotic Susceptibility of Fracture Related Infections in a Low Resource Setting Differ from High Resource Settings: A Cohort Study from Cameroon.

Fracture-related infection (FRI) is a common and devastating complication of orthopedic trauma in all settings. Data on the microbiological profile and susceptibility of FRI to antibiotics in low-income countries are scarce. Therefore, this study aimed to investigate the microbial patterns and antimicrobial susceptibility of FRI in a sub-Saharan African setting in order to provide guidance for the formulation of evidence-based empirical antimicrobial regimens. We conducted a retrospective analysis of patients treated for FRI with deep tissue sampling for microbiological culture from January 2016 to August 2023 in four tertiary-level hospitals in Yaoundé, Cameroon. There were 246 infection episodes in 217 patients. Cultures were positive in 209 (84.9%) cases and polymicrobial in 109 (44.3%) cases. A total of 363 microorganisms from 71 different species were identified, of which 239 (65.8%) were Gram-negative. The most commonly isolated pathogens were Staphylococcus aureus (n = 69; 19%), Enterobacter cloacae (n = 43; 11.8%), Klebsiella pneumoniae (n = 35; 9.6%), Escherichia coli (n = 35; 9.6%), and Pseudomonas aeruginosa (n = 27; 7.4%). Coagulase-negative staphylococci (CoNS) were isolated in only 21 (5.9%) cases. Gram-negative bacteria accounted for the majority of the infections in early (70.9%) and delayed (73.2%) FRI, but Gram-positive bacteria were prevalent in late FRI (51.7%) (p < 0.001). Polymicrobial infections were more frequent in the early (55.9%) and delayed (41.9%) groups than in the late group (27.6%) (p < 0.001). Apart from Staphylococcus aureus, there was no significant difference in the proportions of causative pathogens between early, delayed, and late FRI. This study found striking resistance rates of bacteria to commonly used antibiotics. MRSA accounted for 63% of cases. The most effective antibiotics for all Gram-positive bacteria were linezolid (96.4%), vancomycin (92.5%), clindamycin (85.3%), and fucidic acid (89.4%). For Gram-negative bacteria, only three antibiotics displayed a sensitivity >50%: amikacin (80.4%), imipenem (74.4%), and piperacillin + tazobactam (57%). The most effective empirical antibiotic therapy (with local availability) was the combination of vancomycin and amikacin or vancomycin and imipenem. In contrast to the literature from high-resource settings, this study revealed that in a sub-Saharan African context, Gram-negative bacteria are the most common causative microorganisms of FRI. This study revealed striking resistance rates to commonly used antibiotics, which will require urgent action to prevent antimicrobial resistance in low and middle-income countries.

Studying Microbial Ecology of Diabetic Foot Infections: Significance of PCR Analysis for Prudent Antimicrobial Stewardship.

This study presents a comprehensive investigation into the microbial ecology of diabetic foot infections (DFIs), using molecular-polymerase chain reaction (PCR) analysis to accurately identify the causative agents. One hundred DFI patients were recruited and classified using the Depth Extent Phase and Associated Etiology (DEPA) score according to their severity. Results revealed polymicrobial infections in 75% of cases, predominantly featuring Staphylococcus epidermidis (83%) and Staphylococcus aureus (63%). Importantly, 20% of samples exhibited facultative anaerobes Bacteroides fragilis or Clostridium perfringens, exclusively in high DEPA score ulcers. Candida albicans coinfection was identified in 19.2% of cases, underscoring the need for mycological evaluation. Empirical antimicrobial therapy regimens were tailored to DEPA severity, yet our findings highlighted a potential gap in methicillin-resistant Staphylococcus aureus (MRSA) coverage. Despite an 88% prevalence of methicillin-resistant Staphylococci, vancomycin usage was suboptimal. This raises concerns about the underestimation of MRSA risk and the need for tailored antibiotic guidelines. Our study demonstrates the efficacy of molecular-PCR analysis in identifying diverse microbial communities in DFIs, influencing targeted antibiotic choices. The results advocate for refined antimicrobial guidelines, considering regional variations in microbial patterns and judiciously addressing multidrug-resistant strains. This research contributes crucial insights for optimizing DFIs management and helps the physicians to have a fast decision in selection the suitable antibiotic for each patient and to decrease the risk of bacterial resistance from the improper use of broad-spectrum empirical therapies.

Neuroinvasive Bacillus cereus Infection in Immunocompromised Hosts: Epidemiologic Investigation of 5 Patients With Acute Myeloid Leukemia.

Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen.

1452. Neuroinvasive Bacillus Cereus Infection Amongst Immunocompromised Patients: Epidemiological Investigation of 5 Cases in Patients with Acute Myeloid Leukemia

Abstract Background Bacillus cereus can cause serious nosocomial infections, including neuroinvasive infections in immunocompromised patients. Three patients with AML developed hospital-onset neuroinvasive B. cereus infections in close temporal proximity at our institution in 2022, triggering an extensive epidemiological investigation. Methods We identified all patients with AML, positive microbiologic assays for Bacillus species &amp;gt;48 hours after admission, and neurological symptoms with radiologic findings admitted between January 2018 and October 2022 (Figure 1). Infection control practices were observed, environmental samples obtained, and a dietary case-control study was performed. Bacillus isolates were sequenced, including 2 case isolates, 61 environmental specimens, and 19 samples of a protein supplement common to most AML patients.Figure 1.Case Identification and Definitions Results Five AML patients with B. cereus neuroinvasive disease were identified. Four were identified via blood culture and one via metagenomic sequencing of plasma cell-free DNA. All patients were hospitalized for induction chemotherapy and were neutropenic (Table 1; Figure 2). Central nervous system findings included intraparenchymal and subarachnoid hemorrhage, and rim-enhancing lesions. All patients were treated with ciprofloxacin and survived without neurologic sequelae. B. cereus was positively identified in 7/61 environmental and 1/19 protein samples. There was no single exposure common to all patients per the dietary case-control study, hospital construction records, or environmental samples. Sequencing confirmed all isolates were unrelated. Ciprofloxacin was added to the empiric antimicrobial regimen for AML patients with neutropenic prolonged or recurrent fevers in September 2022; no new cases have since been identified through April 2023 (Figure 3).Table 1.Clinical Characteristics of Neuroinvasive Bacillus Cereus CasesFigure 2.Timeline of Clinical Presentation of Neuroinvasive Bacillus Cereus InfectionFigure 3.Antimicrobial Protocol for Prevention of Neuroinvasive Bacillus Cereus Infection Conclusion B. cereus is ubiquitous in the hospital environment, sometimes leading to pseudoclusters with unrelated isolates. Fastidious infection control practices addressing a broad range of potential exposures are warranted to prevent nosocomial infections. Including B. cereus coverage in empiric regimens for AML patients with prolonged or recurrent neutropenic fever may prevent serious infections from this pathogen. Disclosures Nicolas C. Issa, MD, AiCuris: Grant/Research Support|Astellas: Grant/Research Support|Boehringer Ingelheim: Advisor/Consultant|Fujifilm: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support Chanu Rhee, MD, MPH, Cytovale: Advisor/Consultant|Pfizer: Advisor/Consultant|UpToDate, Inc.: Honoraria Michael Klompas, MD, MPH, UpToDate, Inc.: Royalties for chapters on pneumonia

Antimicrobial resistance patterns and empiric antibiotic selections for patients admitted from post-acute care facilities.

To characterize the susceptibilities of positive bacterial cultures and the appropriateness of empiric antimicrobial regimens for patients admitted from post-acute care facilities (PACFs). This was a retrospective quality improvement study. The study included patients admitted from a PACF to one of 2 tertiary care teaching hospitals within the University of Pennsylvania Health System, located in Philadelphia, PA, from August 2020 to December 2021. Patients were included if they had at least one positive culture within 72 hours of admission. A total of 167 patients and 230 isolates from the study period were evaluated. The majority of positive cultures were from a urinary source (114 of 230, 49.6%). Nineteen patients (11.4%) had a history of multidrug-resistant organisms. The most common empiric antibiotics used were vancomycin (61.7%) and cefepime (59.3%). Sixty-one patients (36.5%) received inappropriate empiric therapy based on the culture results. When comparing our hospitals' general antibiogram to that of only PACF patients, Escherichia coli and Klebsiella pneumoniae had at least a 20% difference in susceptibility to levofloxacin, ceftriaxone, and cefepime. Extended-spectrum β-lactamase resistance was also higher in the PACF cohort (odds ratio, 2.09; 95% confidence interval, 1.4-3.1). Clinically significant differences in antimicrobial susceptibility were found among patients admitted from PACFs compared to our health system's general antibiogram. The increased resistance rates identified in this study support the need for hospitals to evaluate this at-risk patient population, which may drive changes to empiric antibiotic prescribing practices.

The PEST (Pathology, Epidemiology, Severity, Treatment) approach to optimizing antimicrobial therapy

BackgroundSelecting an empiric antimicrobial regimen can be difficult for early learners and misuse of antibiotics can lead to adverse events and antimicrobial resistance. There have been few interventions that have focused on improving antibiotic decision making, as a form of therapeutic reasoning, for post-graduate trainees. We describe here an approach to aid internal medicine interns in their therapeutic reasoning, particularly when it comes to diagnosing and empirically treating infections.MethodsThe PEST (pathology, epidemiology, severity, treatment) model was created as a four-step approach to therapeutic reasoning and choosing an appropriate antimicrobial regimen for a given infectious disease syndrome. In February 2020, we conducted two independent teaching sessions for interns on the PEST approach. We assessed pre-and post-teaching responses to five clinical vignette-based questions. Results were presented as a percentage of interns who chose an appropriate antibiotic and provided sufficient therapeutic reasoning as defined by using at least three out of the four PEST criteria. Statistical analysis occurred via Fischer’s exact test to determine the level of statistical significance between responses.ResultsTwenty-seven interns participated in the activity. At baseline, several interns had incorporated aspects of the PEST approach in their pre-teaching responses. Ten interns commented on the usefulness of such a systematic approach. While there was no statistically significant difference in antibiotic selection, the teaching session demonstrated a trend towards significance in improving therapeutic reasoning as defined by the PEST strategy.ConclusionOur results suggested an improvement in using a structured cognitive tool such as the PEST approach to reinforce therapeutic reasoning, but the method did little to improve antibiotic selection. Some interns used select “PEST” concepts prior to the intervention suggesting that the PEST approach may enhance prior knowledge or clinical reasoning skills. Continued incorporation of the PEST approach using a case-based framework may solidify conceptual and practical knowledge of antimicrobial selection. Further studies are needed to assess the impact of such teaching interventions.

Assessing Empiric Antimicrobial Therapy With the Modified Dundee Classification for Nonpurulent Skin and Soft Tissue Infections in a Community Hospital System.

The modified Dundee classification has recently been validated in various studies for nonpurulent skin and soft tissue infections. This has yet to be applied in the United States and within community hospital settings to optimize antimicrobial stewardship and ultimately patient care. A retrospective, descriptive analysis was performed of 120 adult patients admitted to St. Joseph's/Candler Health System for nonpurulent skin and soft tissue infections between January 2020 and September 2021. Patients were classified into their modified Dundee classes, and frequencies of concordance of their empiric antimicrobial regimens with this classification scheme in the emergency department and inpatient settings were compared, along with possible effect modifiers and possible exploratory measures associated with concordance. Concordance with the modified Dundee classification for the emergency department and inpatient regimens was 10% and 15%, respectively, with broad-spectrum antibiotic use and concordance positively associated with illness severity. Due to substantial broad-spectrum antibiotic use, possible effect modifiers associated with concordance were unable to be validated, and overall no statistically significant differences among exploratory analyses across classification status were observed. The modified Dundee classification can help identify gaps in antimicrobial stewardship and excessive broad-spectrum antimicrobial usage toward optimizing patient care.

Best Practices in the Management of Infectious Complications for Patients With Cancer: Management of Febrile Neutropenia.

Managing infection in patients with neutropenia is a difficult challenge, as fever is often the only clinical symptom. At JADPRO Live 2022, Kyle C. Molina, PharmD, BCIDP, AAVHIP, of the University of Colorado Hospital, discussed the epidemiology and pathophysiology associated with febrile neutropenia in patients with cancer. He reviewed appropriate treatment settings and empiric antimicrobial regimens for a patient and how to formulate a plan to safely de-escalate and target therapy for patients with febrile neutropenia.

Leuconostoc lactis Bacteremia and Neutropenic Fever

Abstract The epidemiology of bacteremic infections in neutropenic patients has shifted from a previous majority involving gram-positive cocci to an increasing preponderance of gram-negative Enterobacteriaceae species and Pseudomonas aeruginosa. Recommended empiric antimicrobial treatment regimens include an antipseudomonal β-lactam or carbapenem agent while considering risk factors for the possibility of extended-spectrum β-lactamase– or carbapenemase-producing organisms. The addition of vancomycin is generally reserved for the chance of gram-positive cocci infection, principally in patients with central intravascular catheters or soft tissue infections. Persistent or breakthrough bacteremia despite receiving this glycopeptide drug should prompt the clinician to contemplate not only the possibility of vancomycin-resistant enterococci, but also other organisms that possess intrinsic resistance vancomycin, including Leuconostoc species.

Comparative analysis of pathogen distribution in patients with fracture-related infection and periprosthetic joint infection: a retrospective study

BackgroundThe purpose of this study is to investigate the microbial patterns of periprosthetic joint infection (PJI) and fracture-related infection (FRI), and guide for the formulation of more accurate empirical antimicrobial regimens based on the differences in pathogen distribution.MethodsA comparative analysis of pathogen distribution was conducted between 153 patients (76 with PJI and 77 with FRI). Predicted analyses against isolated pathogens from two cohorts were conducted to evaluate the best expected efficacy of empirical antimicrobial regimens (imipenem + vancomycin, ciprofloxacin + vancomycin, and piperacillin/tazobactam + vancomycin).ResultsOur study found significant differences in pathogen distribution between the PJI and FRI cohorts. Staphylococci (61.3% vs. 31.9%, p = 0.001) and Gram-negative bacilli (GNB, 26.7% vs. 56.4%, p < 0.001) were responsible for the majority of infections both in the PJI and FRI cohorts, and their distribution in the two cohorts showed a significant difference (p < 0.001). Multi-drug resistant organisms (MDRO) were more frequently detected in the FRI cohort (29.3% vs. 44.7%, p = 0.041), while methicillin-resistant coagulase-negative Staphylococci (MRCoNS, 26.7% vs. 8.5%, p = 0.002) and Canidia albicans (8.0% vs. 1.1%, p = 0.045) were more frequently detected in the PJI cohort. Enterobacter spp. and Acinetobacter baumannii were detected only in the FRI cohort (11.7% and 8.5%, respectively).ConclusionsStaphylococci and GNB were responsible for the majority of infections in both PJI and FRI. Empirical antimicrobial therapy should focus on the coverage of Staphylococci in PJI and GNB in FRI, and infections caused by MDROs should be more vigilant in FRI, while the high incidence of MRCoNS in PJI should be noted, which could guide for the formulation of more accurate empirical antimicrobial regimens. Targeted therapy for FRI caused by A. baumannii and PJI caused by C. albicans needs to be further investigated. Our study reports significant differences in pathogen distribution between the two infections and provides clinical evidence for studies on the mechanism of implant-associated infection.

Evaluation of clinical response to empirical antimicrobial therapy on day 7 and mortality in the intensive care unit: sub-analysis of the DIANA study Japanese data.

The determinants of antimicrobial use and de-escalation in critical care (DIANA) study was an international, multicenter, observational study on antibiotic use in the intensive care unit (ICU). ICU patients ages over 18 years in whom an empiric antimicrobial regimen in Japan was initiated were included. We compared patients who were evaluated as cured or improved ("effective") 7 days after starting antibiotic treatment with patients who were evaluated as deteriorated ("failure"). Overall, 217 (83%) patients were in the effective group, and 45 (17%) were in the failure group. Both the infection-related mortality rate in the ICU and the in-hospital infection-related mortality rate in the effective group were lower than those in the failure group (0% versus 24.4%; P < 0.01 and 0.5% versus 28.9%; P < 0.01, respectively). Assessment of efficacy of empiric antimicrobial treatment on day 7 may predict a favorable outcome among patients suffering from infection in the ICU.

Continuous Infusion of High Doses of Cefepime in Intensive Care Unit: Assessment of Steady-State Plasma Level and Incidence on Neurotoxicity.

Continuous infusion (CI) with high doses of cefepime is recommended in the empirical antimicrobial regimen of critically ill patients with suspected Gram-negative sepsis. This study aimed to determine factors associated with cefepime overdosing and the incidence of cefepime-induced neurotoxicity (CIN) in these patients. We performed a retrospective study including all patients receiving cefepime treatment between January 2019 and May 2022. The plasma level of cefepime defining overdosing was over 35 mg/L. Neurotoxicity was defined according to strict criteria and correlated with concomitant steady-state concentration of cefepime. Seventy-eight courses of cefepime treatment were analyzed. The mean cefepime plasma level at steady state was 59.8 ± 29.3 mg/L, and overdosing occurred in 80% of patients. Renal failure and a daily dose &gt; 5 g were independently associated with overdosing. CIN was present in 30% of patients. In multivariate analysis, factors associated with CIN were chronic renal failure and a cefepime plasma concentration ≥ 60 mg/L. CIN was not associated with mortality. Overdosing is frequent in patients receiving high doses of cefepime by CI. Steady-state levels are higher than targeted therapeutic pharmacokinetic/pharmacodynamic objectives. The risk of CIN is important when the plasma concentration is ≥60 mg/L.

1794. Evaluation of Antimicrobial Susceptibility Patterns for Patients Admitted from Post-Acute Care Facilities in the Philadelphia Region

Abstract Background Antimicrobial resistance is a rapidly emerging threat and antibiograms are a key component in guiding empiric antimicrobial selection. Patients admitted from post-acute care facilities (PACF) are at a heightened risk for infections from multi-drug resistant organisms, posing a challenge for clinicians selecting empiric therapy. It is uncommon for antibiograms to differentiate between sources of admission. This study aimed to characterize culture proven infections and the appropriateness of empiric antimicrobial regimens for patients admitted from PACF in the Philadelphia region. Methods This was a retrospective quality improvement study that included patients admitted from Philadelphia PACF from August 2020 to June 2021. Patients were included if they had at least one positive culture within 72 hours of admission. Appropriate therapy was determined based on a comparison of empiric antimicrobial selection and susceptibilities that resulted from collected cultures. Descriptive statistics were employed for data analysis. Results A total of 106 patients and 154 cultures were evaluated during the study period. The majority of patients received initial empiric coverage for Pseudomonas aeruginosa (79%) and methicillin-resistant Staphylococcus aureus (59%). Over 50% of all cultures had been obtained from urinary sources. Enterococcus spp. were the most commonly isolated gram positive organism (61%) and Escherichia coli was the most common gram negative organism (33%). A portion of patients (32.7%) did not receive appropriate empiric therapy. Discrepancies in susceptibility patterns between our internal antibiogram and PACF patients were most notable for gram negative organisms including decreased levofloxacin susceptibilities to P. mirabilis isolates (89% vs 45%). Other notable discrepancies include decreased meropenem susceptibilities to P. aeruginosa isolates (88% vs 65%). Select susceptibility patterns are reported in Figure 1. Conclusion Antimicrobial susceptibility was discordant amongst patients admitted from PACF in the Philadelphia region compared to our general antibiogram. The increased resistance identified supports a need to re-evaluate empiric prescribing guidelines for this specific population. Disclosures All Authors: No reported disclosures.

Diabetic ketoacidosis and coronavirus disease 2019-associated mucormycosis: a case report

BackgroundMucormycosis is a rare, life-threatening fungal infection that affects immunocompromised hosts. Diabetes mellitus is a common predisposing condition and most often presents with rhino-orbital-cerebral infection. Association with coronavirus disease 2019 infection was revealed following a resurgence in cases of mucormycosis during the second wave of the pandemic wherein poorly controlled diabetes mellitus was the most significant risk factor in the affected population. Rhino-orbital-cerebral mucormycosis has a high mortality rate, and cerebral involvement is a poor prognostic factor. Herein, we report a case of newly diagnosed diabetes mellitus with concurrent coronavirus disease 2019 infection complicated by diabetic ketoacidosis and rhinocerebral mucormycosis at presentation, describe the diagnostic and therapeutic challenges, and discuss the interventions that ultimately resulted in a favorable clinical response.Case presentationWe describe the case of a previously healthy 13-year-old African American female patient with newly diagnosed diabetes mellitus and concurrent severe acute respiratory syndrome coronavirus 2 infection whose disease course was complicated by rhinocerebral mucormycosis. She presented with fever, altered mental status, and Kussmaul respirations and was diagnosed with diabetic ketoacidosis with concern for cerebral edema. Concern for infectious cerebritis arose due to recurring fevers and persistently altered mental status despite correction of her metabolic derangements. This raised concern for infectious cerebritis and prompted evaluation with serial head imaging, lumbar puncture, and initiation of broad empiric antimicrobial regimen. Head imaging revealed an evolving cerebral abscess, and fungal deoxyribonucleic acid was identified on blood metagenomics testing, which ultimately confirmed the diagnosis of rhinocerebral mucormycosis. Treatment was challenging as she required surgical debridement of the frontal lobe and aggressive antifungal therapy complicated by electrolyte derangements and electrocardiogram changes that necessitated modification of the antimicrobial regimen. Despite these challenges and high mortality rate, the patient was discharged from the hospital in stable condition to inpatient rehabilitation service for reconditioning after prolonged hospitalization.ConclusionRhinocerebral mucormycosis mortality is associated with delays in therapeutic interventions, thus a high index of suspicion and early recognition were essential for timely initiation of antifungal therapy and surgical debridement.

Detection of SARS-CoV-2 and HHV-8 from a large pericardial effusion in an HIV-positive patient with COVID-19 and clinically diagnosed Kaposi sarcoma: a case report

BackgroundPericardial effusion is a late manifestation of HIV more commonly observed in individuals with depressed CD4 counts. Although Mycobacterium tuberculosis remains to be one of the most frequently identified pathogens in the pericardial fluid among people living with HIV, less commonly described etiologies include SARS-CoV-2 that causes coronavirus disease and human herpesvirus-8 which is associated with Kaposi sarcoma. Isolation of more than one pathogen in normally sterile sites remains challenging and rare. We report the first documentation of both SARS-CoV-2 and HHV-8 in the pericardial fluid.Case presentationWe present the case of a young man in his 20s with a recent history of clinically diagnosed pulmonary tuberculosis who was admitted for progressive dyspnea and cough. He had multiple violaceous cutaneous lesions on the face, neck, and trunk and diffused lymphadenopathies. He tested positive for SARS-CoV-2 on admission. The patient was clinically diagnosed with pneumonia, Kaposi sarcoma, and HIV/AIDS. Empiric broad spectrum antimicrobial regimen was subsequently initiated. HIV with low CD4 count was confirmed during hospitalization. Echocardiography revealed a large pericardial effusion, in impending cardiac tamponade. Frond-like fibrin strands, extending to the parietal pericardium, were also observed. Pericardiostomy yielded hemorrhagic, exudative effusion with lymphocytic predominance. SARS-CoV-2 and HHV-8 were detected in the pericardial fluid, and bacterial, fungal, and tuberculous studies were negative. The patient had clinical improvement after pericardial drainage. However, despite our best clinical care, he developed a nosocomial infection leading to clinical deterioration and death.ConclusionDetection of SARS-CoV-2 and HHV-8 in the pericardial fluid is rare, and interpretation of their significance in clinical care is challenging. However, coronavirus disease and Kaposi sarcoma must be considered and adequately addressed in immunocompromised adults presenting with large pericardial effusion.

Empirical antimicrobial therapy for bloodstream infections not compliant with guideline was associated with discordant therapy, which predicted poorer outcome even in a low resistance environment

Objectives To characterise all bloodstream infections (BSIs) in a low antimicrobial resistance (AMR) prevalence setting with regard to the appropriateness of empirical antimicrobial therapy, compliance with the national clinical practice guideline, de-escalation practice and outcome. Methods A retrospective observational study including patients aged 18 years admitted to a university hospital in central Norway with positive blood culture in 2019. Results We included 756 BSI episodes in our analysis. Empirical antimicrobial therapy was in accordance with the national guideline in 534 (70.6%), and not in accordance in 190 (25.1%) of the BSI episodes. There was a statistically significant association between compliance with the national guideline and concordant empirical antimicrobial therapy (p = .001). De-escalation of antimicrobial therapy was possible but not done in 217 (31.1%) of the BSI episodes. Variables identified as independent predictors of discordant empirical antimicrobial therapy included hospital department, type of empirical antimicrobial regimen, bacterial species, and AMR. Independent predictors of intra-hospital case fatality rate were coverage of empirical antimicrobial therapy, CCI-score, SAPS-II score, site of infection, and type of empirical antimicrobial regimen. Furthermore, the intra-hospital and long-term unadjusted all-cause case fatality rates were increased (p < .001, log-rank test for overall difference in survival) for the patients who received discordant empirical antimicrobial therapy. Conclusion Our study shows that empirical antimicrobial therapy initiated in accordance with national guideline recommendations increases the likelihood of receiving concordant therapy. Discordant empirical antimicrobial therapy was associated with poorer outcomes, even in a setting with low AMR prevalence.

Effective antimicrobial therapies of urinary tract infection among children in low-income and middle-income countries: protocol for a systematic review and meta-analysis

IntroductionUrinary tract infection (UTI) is a frequently diagnosed infection in women and children. Treatments are often initiated with broad-spectrum antibiotics without performing any culture and sensitivity test. Inappropriate and empirical...