To Trimethoprim-sulfamethoxazole Research Articles

Associations between neighbourhood-level median household income and outpatients' risk of antibiotic non-susceptible uropathogens in a major urban centre, USA.

Resistance to first-line antibiotics among urinary tract infections continues to rise, but how neighbourhood-level socioeconomic status impacts this risk remains unclear. We examined the effect of neighbourhood-level income on a patient's risk of having a uropathogen non-susceptible to trimethoprim/sulfamethoxazole (TMP/SMX) or nitrofurantoin. We used electronic health record data and antibiotic susceptibility test results for urinary Escherichia coli and Klebsiella pneumoniae collected at Emory Healthcare outpatient facilities in greater Atlanta between October 2022 and September 2023. We determined patients' block group median household income (MHI) using their residential addresses and 2017-21 US census data. We performed a logistic regression with a priori risk factors using a generalized estimating equation, with subgroup analysis by organism and for patients with diabetes mellitus. We included 9325 urine E. coli and K. pneumoniae isolates from 3867 outpatients. Compared to uropathogenic E. coli, K. pneumoniae were more likely to be non-susceptible to nitrofurantoin (P < 0.001) and less likely to be non-susceptible to TMP/SMX (P < 0.001). Compared to the lowest MHI quintile, patients in the highest MHI quintile neighbourhoods had 0.78 odds of harbouring a non-susceptible uropathogen (95% CI: 0.64, 0.95) after controlling for patient age, sex and race/ethnicity, along with neighbourhood-level characteristics. This association was stronger for K. pneumoniae infections and non-significant among people with diabetes. Higher neighbourhood-level MHI was associated with lower individual risk of harbouring a first-line antibiotic-non-susceptible uropathogen.

Outcomes of transplant recipients with pretransplant Nocardia colonization or infection.

Specific pretransplant infections have been associated with poor posttransplant outcomes. However, the impact of pretransplant Nocardia isolation has not been studied. We performed a retrospective study from three centers in Arizona, Florida, and Minnesota of patients with Nocardia infection or colonization who subsequently underwent solid organ or hematopoietic stem cell transplantation from November 2011 through April 2022. Outcomes included posttransplant Nocardia infection and mortality. Nine patients with pretransplant Nocardia were included. Two patients were deemed colonized with Nocardia, and the remaining seven had nocardiosis. These patients underwent bilateral lung (N = 5), heart (N = 1), heart-kidney (N = 1), liver-kidney (N = 1), and allogeneic stem cell transplantation (N = 1) at a median of 283 (interquartile range [IQR] 152-283) days after Nocardia isolation. Two (22.2%) patients had disseminated infection, and two were receiving active Nocardia treatment at the time of transplantation. One Nocardia isolate was resistant to trimethoprim-sulfamethoxazole (TMP-SMX) and all patients received TMP-SMX prophylaxis posttransplant, often for extended durations. No patients developed posttransplant nocardiosis during a median follow-up of 1.96 (IQR 0.90-6.33) years. Two patients died during follow-up, both without evidence of nocardiosis. This study did not identify any episodes of posttransplant nocardiosis among nine patients with pretransplant Nocardia isolation. As patients with the most severe infections may have been denied transplantation, further studies with larger sample sizes are needed to better analyze any impact of pretransplant Nocardia on posttransplant outcomes. However, among patients who receive posttransplant TMP-SMX prophylaxis, these data suggest pretransplant Nocardia isolation may not impart a heightened risk of posttransplant nocardiosis.

Clinical Risk Scores to Predict Nonsusceptibility to Trimethoprim-Sulfamethoxazole, Fluoroquinolone, Nitrofurantoin, and Third-Generation Cephalosporin Among Adult Outpatient Episodes of Complicated Urinary Tract Infection.

Clinical risk scores were developed to estimate the risk of adult outpatients having a complicated urinary tract infection (cUTI) that was nonsusceptible to trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolone, nitrofurantoin, or third-generation cephalosporin (3-GC) based on variables available on clinical presentation. A retrospective cohort study (1 December 2017-31 December 2020) was performed among adult members of Kaiser Permanente Southern California with an outpatient cUTI. Separate risk scores were developed for TMP-SMX, fluoroquinolone, nitrofurantoin, and 3-GC. The models were translated into risk scores to quantify the likelihood of nonsusceptibility based on the presence of final model covariates in a given cUTI outpatient. A total of 30 450 cUTIs (26 326 patients) met the study criteria. Rates of nonsusceptibility to TMP-SMX, fluoroquinolone, nitrofurantoin, and 3-GC were 37%, 20%, 27%, and 24%, respectively. Receipt of prior antibiotics was the most important predictor across all models. The risk of nonsusceptibility in the TMP-SMX model exceeded 20% in the absence of any risk factors, suggesting that empiric use of TMP-SMX may not be advisable. For fluoroquinolone, nitrofurantoin, and 3-GC, clinical risk scores of 10, 7, and 11 predicted a ≥20% estimated probability of nonsusceptibility in the models that included cumulative number of prior antibiotics at model entry. This finding suggests that caution should be used when considering these agents empirically in patients who have several risk factors present in a given model at presentation. We developed high-performing parsimonious risk scores to facilitate empiric treatment selection for adult outpatients with cUTIs in the critical period between infection presentation and availability of susceptibility results.

Device-associated Meningitis due to Elizabethkingia meningoseptica: A Therapeutic Challenge.

To the Editors: Elizabethkingia meningoseptica causes life-threatening infections in humans, especially in immunocompromised patients and infants with low birth weights. It is one of the main causes of meningitis in pediatric and immunocompromised patients in the context of nosocomial diseases associated with devices and is also related to low-birth-weight infants and prematurity1 Due to their resistance to many commonly used antibiotics (beta-lactams, carbapenemics, aminoglycosides, etc.), clinicians face treatment challenges.2 There are currently few publications on pediatric cases regarding E. meningoseptica device-associated meningitis with breakthrough resistance to trimethoprim-sulfamethoxazole (TMP/SMX) while treatment with dual intravenous (IV) therapy with TMP/SMX and high-dose ciprofloxacin requiring intraventricular ciprofloxacin for eradication. This letter is written to describe a case that posed a diagnostic challenge in our center. A 1-month-old female patient with hydrocephalus secondary to a history of myelomeningocele that required correction at birth with a ventriculoperitoneal (VP) shunt system presented during her prolonged hospitalization with device-associated meningitis due to E. meningoseptica initially susceptible to TMP/SMX MIC <16 µg/L, follow-up cerebrospinal fluid (CSF) cultures remained positive for the same pathogen with TMP/SMX breakthrough resistance acquired (MIC > 64 µg/L) (Table 1). Different antibiotics were tested in vitro and showed resistance to vancomycin, minocycline, and rifampicin, maintaining only susceptibility to ciprofloxacin without achieving eradication with systemic dual high-dose IV therapy. TABLE 1. - Cerebrospinal Fluid Culture Analyzed in Vitek2 System (Biomérieux) Initial Control Antibiotic Value/Interpretation Value/Interpretation Amikacin ≥64 µg/mL (R) ≥64 µg/mL (R) Aztreonam ≥64 µg/mL (R)) Cefazolin ≥64 µg/mL (R) Cefepime ≥64 µg/mL (R) ≥64 µg/mL (R) Ceftazidime ≥64 µg/mL (R) ≥64 µg/mL (R) Ceftriaxone ≥64 µg/mL (R) Ciprofloxacin ≥1 µg/mL (Susceptible) ≥1 µg/mL (S) Gentamicin ≥16 µg/mL (Resistant) ≥16 µg/mL (R) Meropenem ≥64 µg/mL (Resistant) ≥64 µg/mL (R) Piperacillin/tazobactam 32 µg/mL (Susceptible) ≥128 µg/mL (R) Tigecycline 1 µg/mL (S) ≥8 µg/mL (R) Trimethoprim/sulfamethoxazole (TMP/SMX) 40 µg/mL (S) ≥320 µg/mL (R) Colistin ≥16 µg/mL (R) Doripenem ≥8 µg/mL (R) Imipenem ≥16 µg/mL (R) (R), resistant; (S), susceptible. Intraventricular antimicrobial therapy with ciprofloxacin was proposed based on a case report in the literature: 21 days of systemic treatment combined with Intrathecal therapy, and another 21 days of systemic therapy alone. Negative CSF cultures were obtained after 6 days of dual therapy plus intraventricular ciprofloxacin with clinical improvement in the patient and replacement of the VP shunt. Although recent literature suggests that antibiotics such as fluoroquinolones can achieve good concentrations in the CSF fluid after IV administration and do not suggest their use in intraventricular or intrathecal routes,3 and that the FDA has not approved any antimicrobial agent for intraventricular use,3,4 when therapeutic options are limited due to multidrug-resistant pathogens in central nervous system infections, intraventricular/intrathecal antibiotic therapy with fluoroquinolones appears to be a viable option in the absence of other available treatments. More studies are required, particularly in cases, such as the one presented for antibiotics that theoretically achieve adequate CSF concentrations when only IV route is used.

Inborn Error of Immunity Presenting with Salmonella Pericarditis and Pericardial Effusion

Salmonella infections typically occur in disorders of innate immunity with impairment in phagocyte function and/or impaired signaling in the IL-12/interferon (IFN)-gamma axis. Pericarditis/pericardial effusion has previously been reported as a rare complication of Salmonella infection.An 8-year-old, previously healthy, fully immunized Hispanic female presented with 4 days of fever and 5 days of pain in her chest, abdomen, and left shoulder. Her medical and family history was unremarkable. Chest radiograph revealed cardiomegaly, and a transthoracic echocardiogram identified a large pericardial effusion. Labs showed leukocytosis (15 K/uL), neutrophilia (ANC 12.77 K/uL), elevated CRP (287 mg/dL), and elevated BNP (607 pg/mL). Exam showed mild distress, gallop on cardiac auscultation, diminished left breath sounds, cool extremities, and 1+ peripheral pulses. She underwent pericardiocentesis, and the fluid culture was positive for Salmonella alachua. She was treated with IV ceftriaxone for 8 days, then transitioned to trimethoprim/sulfamethoxazole (TMP/SMX) to complete a 30-day total antibiotic course.Inpatient immunologic evaluation revealed T cell lymphopenia (TCL) with decreased naïve CD4+ and CD8+ T cells. Increased CD4+ and CD8+ effector memory T cells (Tem) were also observed, along with increased CD8+ TEMRA, and certain subsets of CD4+/CD8+ central memory T cells lacking CD62L. HIV testing and neutrophil oxidative burst were negative. Given her significant T cell lymphopenia, TMP/SMX prophylaxis was continued after the treatment course, and fluconazole prophylaxis was initiated due to endemic coccidiomycosis.A targeted 429-gene panel for inborn errors of immunity revealed a heterozygous missense variant of uncertain significance in PIK3CD, = c.1013G>A, p.Arg338Gln. This variant is not in gnomAD for Hispanics and is present in 0.0009% of non-Finnish Europeans. Gain-of-function (GoF) PIK3CD mutations cause a combined immunodeficiency, with increased risk of infection from encapsulated organisms, such as salmonella. However, the patient’s immunophenotype is not consistent with GoF PIK3CD mutation. She had normal transitional B cells, lack of increased senescent T cells, and absence of lymphoproliferation.TCL is likely an immunologic risk factor for Salmonella pericarditis with pericardial effusion. Though the PI3CKD variant does not appear to be pathogenic, additional functional testing for this variant is in progress.

The Impact of Patient Age and Corticosteroids in Patients With Sulfonamide Hepatotoxicity.

Sulfonamides are widely used to treat and prevent various bacterial and opportunistic infections. The aim of this study was to describe the clinical presentation and outcomes of a large cohort of patients with sulfonamide hepatotoxicity. Between 2004 and 2020, 105 patients with hepatotoxicity attributed to trimethoprim/sulfamethoxazole (TMP-SMZ) (n = 93) or other sulfonamides (n = 12) were enrolled. Available liver biopsies were reviewed by a single hepatopathologist. Among the 93 TMP-SMZ cases, 52% were female, 7.5% younger than 20 years, and the median time to drug-induced liver injury (DILI) onset was 22 days (range: 3-157). Younger patients were significantly more likely to have rash, fever, eosinophilia, and a hepatocellular injury pattern at onset that persisted at the peak of liver injury compared with older patients ( P < 0.05). The 18 (19%) TMP-SMZ patients treated with corticosteroids had more severe liver injury and a higher mortality but a trend toward more rapid normalization of their laboratory abnormalities compared with untreated patients. During follow-up, 6.2% of the TMP-SMZ patients died or underwent liver transplantation. Chronic DILI developed in 20% and was associated with cholestatic injury at onset and higher peak total bilirubin levels. Sulfonamide hepatotoxicity is characterized by a short drug latency with frequent hypersensitivity features at onset. Subject age is an important determinant of the laboratory profile at presentation, and patients with cholestasis and higher total bilirubin levels were at increased risk of developing chronic DILI. Corticosteroids may benefit a subgroup of patients with severe injury, but further studies are needed.

A Case of Sphingobacterium multivorum Bloodstream Infection in a Critically-Ill Patient.

Sir, Sepsis in intensive care units (ICUs) is common in immunocompromised individuals; herein, we discuss with the help of a case of sepsis due to Sphingobacteriummultivorum in an uncontrolled diabetic individual. A 40-year-old male with poorly controlled diabetes mellitus presented to our ICU with right thigh cellulitis and diabetic ketoacidosis (DKA). Subsequently, he developed inferior wall myocardial infarction and right ventricular dysfunction. On examination, he was in altered sensorium, hemodynamically unstable, and had respiratory distress. He was managed for all the above-mentioned issues, which comprised management of DKA and acute coronary syndrome (dual anti-platelets, heparin, statins) and included life support therapies in the form of invasive mechanical ventilation, central line placement, IV fluid resuscitation (guided by two-dimensional echocardiography, lung ultrasonography, and hemodynamic and oxygenation parameters), vasoactive drugs and other drugs such as anti-platelets, therapeutic heparinization, and IV insulin infusion for glycemic control (with emphasis on electrolytes also). The patient stayed in ICU for a prolonged period due to neuromuscular weakness, nosocomial infections, and ischemic cardiomyopathy. Later on, he developed a grade III sacral bedsore also. One of the bugs was S. multivorum cultured from his peripheral blood during an episode of high-grade fever. S. multivorum is a rare but important cause of bloodstream infection in critically ill populations. The bacterium is categorized under the genus Sphingobacterium (formerly known as Flavobacterium) are nonfermenting, catalase and oxidase positive, nonmotile, nonspore-forming Gram-negative rod, naturally found in soil, water, and plant materials.[1] Their nomenclature is secondary to the presence of large quantities of cellular sphingolipids. These rarely cause human diseases, but still, there are certain case reports about their association with infections like respiratory tract infections in patients with cystic fibrosis, soft-tissue infections, septicemia in hemodialysis patients, and meningitis.[2] The two species most commonly implicated are S. spiritivorum and S. multivorum. These are commonly found as commensals on human skin and predispose immunocompromised individuals to infections. However, there are case reports published about Sphingobacterium leading to cellulitis in an immunocompetent person also. In this patient, the isolate was S. multivorum which had led to bacteremia after 6 weeks of ICU stay. To our knowledge, this is the third rare case from India regarding S. multivorum infection in health-care settings. The probable source could have been the grade IV infected sacral bedsore. The bacterium was sensitive to piperacillin/tazobactam and levofloxacin and was resistant to ceftazidime, amikacin, imipenem, carbapenem, and aztreonam. The patient was also sensitive to trimethoprim/sulfamethoxazole (TMP/SMX) and was treated with (TMP/SMX). Sensitivity to other antibiotics was not done. The sensitivity profile of S. multivorum in some case reports depicts in Table 1.Table 1: Sensitivity of sphingobacterium multivorum isolates in case reportsThe information given in our case may be helpful in broadening our knowledge about infections with such bacteria. As these bacteria are rarely causative, though they have the capability to cause infection in immunocompetent individuals, hence these bacteria cannot be fully ignored. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

2233. Clinical Risk Scores (CRSs) to Predict Resistance to Trimethoprim-Sulfamethoxazole (TMP-SMX), Fluoroquinolone (FQ), Nitrofurantoin (NIT), or Third Generation Cephalosporins (3GC) among Adult Outpatients (OPs) with Complicated Urinary Tract Infections (cUTIs)

Abstract Background Increased resistance rates to available oral antibiotics (ABs) contribute to delays in receipt of appropriate treatment and adverse outcomes among patients with cUTI in the OP setting. To optimize empiric AB selection in adult OPs with cUTIs, we developed CRSs using information available at presentation to estimate the risk of having a cUTI that was resistant to TMP-SMX, FQ, NIT, or 3GC. Methods Retrospective cohort study among Kaiser Permanente Southern California members from 2017-2020. Inclusion criteria: age ≥18 yrs; cUTI diagnosis during an OP visit; positive urine culture with antibiotic susceptibility results; receipt of antibiotic ±3 days of index urine culture, and not hospitalized on day of OP visit. Resistance to TMP-SMX, FQ, NIT, and 3GC on index urine culture was quantified. OPs were randomly split (60:40) into training and validation datasets. Covariates present on clinical presentation were collected. Least absolute shrinkage and selection operator logistic regression (LR) were used to develop separate models to estimate the likelihood of resistance to TMP-SMX, FQ, NIT, and 3GC. The prediction models were developed using training and validation datasets. For all 4 LR models, CRSs were calculated as the weighted sums of regression coefficients. Variables in each of the final LR models were assigned point(s), and an OP’s CRS for cUTI resistant to TMP-SMX, FQ, NIT, or 3GC was based on total points in each of the respective models. Results A total of 30,450 cUTIs among 26,326 OPs met study criteria. Mean age was 61, 54% were female, and E. coli (66%) was the most common pathogen. Resistance to TMP-SMX, FQ, NIT, and 3GC was 37%, 27%, 24%, and 19%, respectively. Baseline covariates and associated points for the 4 LR models are shown in Table 1. A CRS of 0, 5, 8, 12 corresponded to a &amp;gt;20% risk of resistance to TMP-SMX, FQ, NIT, or 3GC, respectively (Figure 1). Table 1.Baseline Clinical Covariates and Associated Point Values in Each of the 4 Clinical Risk Scores Covariates in each of the Final ResistanceFigure 1.Clinical Risk Scores for Resistance to TMP-SMX, FQ, NIT, and 3GC Conclusion We developed a high-performing parsimonious CRS to aid clinicians in appropriate treatment selection of adult OPs with cUTI. This tool can be used to facilitate empiric antibiotic selection and ensure adult OPs with cUTI have a greater probability of receiving early appropriate therapy. Given its high baseline resistance, TMP/SMX should not be considered for empiric therapy. Disclosures Thomas P. Lodise, PharmD, PhD, Spero Therapeutics: Advisor/Consultant Lie Hong H. Chen, DrPH, MSPH, Spero Therapeutics: Grant/Research Support Katia J. Bruxvoort, PhD, MPH, Dynavax: Grant/Research Support|Gilead: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Seqirus: Grant/Research Support Rong Wei, MA, Spero Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support Theresa M. Im, MPH, Spero Therapeutics: Grant/Research Support Richard Contreras, MS, Spero Therapeutics: Grant/Research Support Mauricio Rodriguez, PharmD, MS-HEOR, BCPS, BCCCP, BCIDP, Spero Therapeutics: Employee Larry Friedrich, PharmD, Spero Therapeutics: Employee Jennifer Reese, PharmD, Spero Therapeutics: Employee Sara Y. Tartof, PhD MPH, Pfizer: Grant/Research Support|Spero: Grant/Research Support.

2004. Contemporary Clinical Epidemiology of Pediatric Shigella spp. Infections in Houston, TX, 2016-2021

Abstract Background Infections due to Gram-negative pathogens that cause gastrointestinal illnesses are a significant cause of morbidity in children. The contemporary clinical and epidemiological features of pediatric Shigella spp. infections in urban cities in the United States are not well described. Methods We used a retrospective cohort of patients (0-18 years of age) from a network of hospitals in Houston, TX. Only patients with Shigella spp. isolated from clinical samples dated from 2016 to 2021 were included in the study. Demographic, clinical, and microbiological data and susceptibility profile were extracted from the medical record. Results We identified a total of 73 pediatric patients with Shigella spp. Infections. The median age at presentation was 5 years. Hospital admission occurred in 32 % of infections with a median length of stay of 1 day (Table 1). Of cases with available clinical data, 80% of patients with Shigella spp. infections reported fever (Table 2). Of note, 62% of patients developed bloody diarrhea (Table 2). The majority of patients infected with Shigella flexneri (4/7) reported a history of international travel. Seizures were observed in 5 patients. No episodes of bacteremia were identified. Among patients with an identified exposure, daycare attendance and contact with individuals experiencing similar symptoms were the most common (Table 2). The majority of Shigella species were S. sonnei (90.4%) (Table 3). Resistance to trimethoprim-sulfamethoxazole (TMP-SMX) was common (45/68, 66%) among Shigella spp. isolates tested. No resistance to third generation cephalosporins was observed. (Table 3). Although azithromycin was the most common antibiotic used for treatment, susceptibility testing for this antibiotic was not performed in any of the cases. Conclusion Infections due to Shigella spp. are a significant burden among pediatric patients in a major metropolitan health care system (Houston, TX). Bloody diarrhea was the most common presentation, although the presence of Shiga-toxin-positive isolates was unknown. The observed high frequency of resistance to TMP-SMX and emergence of multi-drug resistant Shigella spp. in other countries warrants continued surveillance. Disclosures Cesar A. Arias, MD, PhD, Entasis Phramceuticals: Grant/Research Support|MeMed Diagnostics: Grant/Research Support|Merck: Grant/Research Support.

1797. Evaluation of Intravenous vs Oral Antibiotic Therapy at Discharge for the Treatment of Urinary Source Gram-Negative Bacteremia

Abstract Background Retrospective studies demonstrate similar efficacy between oral (PO) and intravenous (IV) antibiotics at discharge for gram negative bacteremia (GNB), with reduced duration of hospitalization, hospital costs, and duration of therapy with PO. Understanding current physician discharge practices can help guide future antimicrobial stewardship initiatives. Methods A multicenter, retrospective cohort study was conducted on adult inpatients admitted between July 1, 2020 and June 30, 2021 with urinary source GNB. Patients with both blood and urine cultures positive for Escherichia coli, Klebsiella species, or Proteus mirabilis and a PO antibiotic available at discharge were included. The primary outcome was the percentage of patients discharged on PO antibiotics. Secondary outcomes included duration of hospitalization, total length of therapy, and 30-day readmission secondary to clinical failure or therapeutic complication in the IV and PO at discharge groups. Results Of the 157 included patients, 128 (82%) were discharged on PO antibiotics. Patients discharged on IV and PO had similar median quick Pitt bacteremia scores [1(IQR, 0 – 2) vs. 1 (IQR, 0 – 1), p=0.420]. Mean duration of hospitalization for patients discharged on IV vs. PO therapy was 5 (SD, 2.91) days vs. 4 (SD, 2.75) days, p=0.001, respectively. Mean total length of antibiotic therapy was 21.6 (SD, 13.80) days as compared to 13.5 (SD, 4.94) days, p=0.017, for the IV vs. PO arms, respectively. Thirty–day readmission rates were 11/29 (38%) and 23/128 (18%), p=0.035, in the IV and PO arms, respectively. Notably, 21/29 (72%) of the IV arm had an organism from blood culture that was susceptible to trimethoprim-sulfamethoxazole (TMP-SMX). Conclusion Most patients with urinary source GNB were discharged on PO antibiotics. Patients discharged on IV antibiotics were more likely to be readmitted within 30 days. Future efforts to decrease IV antibiotic use may focus on increasing TMP-SMX use at discharge. Disclosures Matthew Song, PharmD, BCIDP, Merck: Stocks/Bonds|ObsEva: Stocks/Bonds.

Antibiotic Susceptibility and Minimum Inhibitory Concentration for Stenotrophomonas maltophilia Ocular Infections.

Stenotrophomonas maltophilia (S. maltophilia) is a Gram-negative, opportunistic pathogen that can lead to ocular infections, such as keratitis and endophthalmitis. The purpose of this study was to determine the antibiotic susceptibility and minimum inhibitory concentrations (MICs) of S. maltophilia isolates from ocular infections and to evaluate the differences in antibiotic MICs between keratitis and endophthalmitis isolates. The disc diffusion method revealed that S. maltophilia isolates exhibited 91% susceptibility to levofloxacin and moxifloxacin and 61% susceptibility to trimethoprim−sulfamethoxazole (TMP−SMX). The E-test indicated that S. maltophilia isolates exhibited 40%, 100%, 72%, 91%, 91%, and 93% susceptibility to ceftazidime, tigecycline, TMP−SMX, levofloxacin, gatifloxacin, and moxifloxacin, respectively. The MIC90 values of amikacin, ceftazidime, cefuroxime, tigecycline, TMP−SMX, levofloxacin, gatifloxacin, and moxifloxacin were >256, >256, >256, 3, >32, 1, 2, and 0.75 µg/mL, respectively. The geometric mean MICs of ceftazidime, TMP−SMX, levofloxacin, gatifloxacin, and moxifloxacin were significantly lower for the keratitis isolates than for the endophthalmitis isolates (p = 0.0047, 0.003, 0.0029, 0.0003, and 0.0004, respectively). Fluoroquinolones showed higher susceptibility and lower MICs for the S. maltophilia isolates when compared with other antibiotics. Fluoroquinolones can be recommended for treating S. maltophilia ocular infections. Tigecycline and TMP−SMX could be alternative antibiotics for S. maltophilia ocular infections.

Case Report of Nocardial Brain Abscess in a Patient on Steroids

Nocardial brain abscesses are a rare cause of cerebral abscesses that usually arise in immunocompromised patients and are associated with high morbidity and mortality. We present the case of a 57-year old male who presented with fever, progressive vision loss and disorientation in the emergency room while on treatment for community acquired pneumonia. He has been using steroids for 20 years and has uncontrolled diabetes mellitus, and secondary adrenal insufficiency as a result. Chest computed tomography (CT) showed consolidation in left posterior-inferior lobe. Blood and cerebrospinal fluid (CSF) cultures were negative. Magnetic resonance imaging (MRI) of the head revealed multiple small dispersed lesions with peripheral ring enhancement after contrast administration, concerning for abscesses. Pus was sampled from a superficial occipital abscess and content grew Nocardia sensitive to trimethoprim/sulfamethoxazole (TMP/SMX) and imipenem so the patient was switched to targeted therapy. The following days he developed new motor deficits and became unresponsive to verbal stimulus. Another MRI revealed enlargement of the existing lesions and new lesions with signal restriction on diffusion (DWI) in the levels of the midbrain and pons. The patient developed respiratory insufficiency and passed away regarding of ongoing supportive treatment.

Revisiting the Evidence Base for Modern-Day Practice of the Treatment of Toxoplasmic Encephalitis: A Systematic Review and Meta-Analysis.

Toxoplasmic encephalitis (TE) is an opportunistic infection of people with human immunodeficiency virus (HIV) or other causes of immunosuppression. Guideline-recommended treatments for TE are pyrimethamine and sulfadiazine (P-S) or pyrimethamine and clindamycin (P-C); however, a substantial price increase has limited access to pyrimethamine. Consequently, some centers have transitioned to trimethoprim-sulfamethoxazole (TMP-SMX), an inexpensive alternative treatment. We aimed to review the evidence on the efficacy and safety of pyrimethamine-containing therapies vs TMP-SMX. We searched for and included randomized controlled trials (RCTs) and observational studies of TE treatments, regardless of HIV status. Data for each therapy were pooled by meta-analysis to assess the proportions of patients who experienced clinical and radiologic responses to treatment, all-cause mortality, and discontinuation due to toxicity. Sensitivity analyses limited to RCTs directly compared therapies. We identified 6 RCTs/dose-escalation studies and 26 single-arm/observational studies. Identified studies included only persons with HIV, and most predated modern antiretroviral treatment. Pooled proportions of clinical and radiologic response and mortality were not significantly different between TMP-SMX and pyrimethamine-containing regimens (P > .05). Treatment discontinuation due to toxicity was significantly lower in TMP-SMX (7.3%; 95% confidence interval [CI], 4.7-11.4; I2 = 0.0%) vs P-S (30.5%; 95% CI, 27.1-34.2; I2 = 0.0%; P < .01) or P-C (13.7%; 95% CI, 9.8-18.8; I2 = 32.0%; P = .031). These results were consistent in analyses restricted to RCT data. TMP-SMX appears to be as effective and safer than pyrimethamine-containing regimens for TE. These findings support modern RCTs comparing TMP-SMX to pyrimethamine-based therapies and a revisiting of the guidelines.

Community-acquired bacteraemia by Klebsiella pneumoniae producing KPC-3 and resistant to ceftazidime/avibactam

To describe the clinical and microbiological features of a case of community-acquired infection by KPC-producing K. pneumoniae (KPCKP) resistant to ceftazidime/avibactam (CAZ-AVI). Identification of microorganisms was performed with MALDI Biotyper CA System (BrukerDaltonics, Madrid, Spain). Antimicrobial susceptibility testing was performed using Sensitre EURGNCOL panels (Thermo Fisher Scientific, Madrid, Spain) and gradient strips (Etest, bioMérieux, Madrid, Spain) in the case of CAZ-AVI, using EUCAST breakpoints for interpretation. Whole genome sequencing of blood culture and rectal swab isolates was performed using the Illumina NovaSeq 6000 sequencing system, with 2×150-bp paired-end reads (Illumina, Inc.). Blood culture and rectal swab KPCKP isolates were resistant to carbapenems and to CAZ-AVI. The blood culture isolate showed susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX), but the rectal swab culture isolate was resistant to this antibiotic. Both isolates belonged to clonal lineage ST512, harboured a single copy of blaKPC-3 gene, and showed 16 single nucleotide polymorphisms (SNP) between them and 38 SNPs with regard to the first KPC-3 producing K. pneumoniae isolated in our hospital in an initial outbreak in 2012. Genome-wide resistome analysis revealed the presence of a IncFIB(K) plasmid harbouring sul1 and dfrA12 genes only in the rectal swab culture isolate, which may explain its resistance to TMP-SMX. Resistance to ceftazidime-avibactam is an emerging nosocomial problem. This case shows that CAZ-AVI-resistant KPCKP strains may disseminate into the community and cause serious infections.

Stenotrophomonas Maltophilia and Urinary Tract Infections: A Systematic Review.

Stenotrophomonas maltophilia, a gram-negative bacillus well known to cause respiratory tract infections, is increasingly being reported to cause urinary tract infections (UTI). In our review of the literature comprising six articles, males were more prone to developing UTIs, with the mean age of the patients being 62.5 ±18.9 years. While several risk factors have been associated with the development of the disease, patients with underlying urological or nephrological diseases tend to develop a more severe illness. The organism was sensitive to trimethoprim-sulfamethoxazole (TMP-SMX) in the majority of cases. This systematic review also aims to shed light on the possible mechanisms of resistance adopted by the bacteria, modes of transmission, and strategies to prevent the transmission and development of the disease.

PD21-11 WITHIN STATE VARIABILITY OF ANTIMICROBIAL SUSCEPTIBILITY: MISSOURI AS AN ARCHETYPE TO ASSESS GUIDELINES FOR ANTIMICROBIAL PROPHYLAXIS FOR TRANSURETHRAL PROCEDURES

You have accessJournal of UrologyCME1 May 2022PD21-11 WITHIN STATE VARIABILITY OF ANTIMICROBIAL SUSCEPTIBILITY: MISSOURI AS AN ARCHETYPE TO ASSESS GUIDELINES FOR ANTIMICROBIAL PROPHYLAXIS FOR TRANSURETHRAL PROCEDURES Corbin Wright, Geoffrey Rosen, Shubham Kanake, Mojgan Golzy, and Katie Murray Corbin WrightCorbin Wright More articles by this author , Geoffrey RosenGeoffrey Rosen More articles by this author , Shubham KanakeShubham Kanake More articles by this author , Mojgan GolzyMojgan Golzy More articles by this author , and Katie MurrayKatie Murray More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002559.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The American Urological Association has developed recommendations for antimicrobial prophylaxis for transurethral (TU) procedures. Specific regimens are advised, with the guidance for urologists to check their local antibiograms. Here, we use Missouri to examine the presence and variability in antibiograms within a state, helping to show the ease with which a urologist may consider a local antibiogram. METHODS: All hospitals in the state of Missouri were identified using the American Hospital Directory and contacted to request antibiograms. Hospital characteristics including bed-size, location, and rurality were collected. Based on results of our prior antibiogram work, we studied E. coli, Klebsiella, and Proteus. We evaluated susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX), Third generation cephalosporins, cefazolin, penicillin combinations, gentamicin and fluoroquinolones. We looked at overall variability and looked for association with hospital bed-size, location, and rurality. RESULTS: Eighty-two hospitals were contacted, and data is included from thirty-nine (48% response rate). Susceptibility of relevant microbes to frequently used antimicrobials is displayed in Table 1. The only statistically significant correlation between hospital characteristics and susceptibility was between increased hospital bed-size and E. coli resistance to penicillin combinations (P=0.001; R-squared=0.47). CONCLUSIONS: Prior work has shown low susceptibility of common infectious agents after TU procedures to first-line recommended prophylactic antimicrobials. Here, we apply similar methods to a study of hospitals in Missouri. First-line recommendations have low coverage, 82% mean susceptibility for E. coli for 1st generation cephalosporins and 78% for TMP-SMX. Third generation cephalosporins showed high susceptibilities, as did gentamicin. Current recommendations for TU prophylaxis advise use of local antibiograms, yet we were unable to acquire antibiograms from more than half of contacted hospitals. Urologists should consider local patterns when selecting antimicrobials for TU procedure prophylaxis. If not possible, broader-spectrum antimicrobials than current recommendations may be useful. Source of Funding: NA © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e365 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Corbin Wright More articles by this author Geoffrey Rosen More articles by this author Shubham Kanake More articles by this author Mojgan Golzy More articles by this author Katie Murray More articles by this author Expand All Advertisement PDF DownloadLoading ...

The Importance of Early Recognition: a Case of DRESS Syndrome

This case examines the presentation, diagnosis, and treatment of an otherwise healthy 22-year-old female who presented to urgent care with abdominal pain and fever 27 days after her first exposure to trimethoprim/sulfamethoxazole (TMP/SMX). However, this exposure was not recognized for an extended amount of time. She was initially diagnosed with gastroenteritis and sent home on metronidazole. She failed to improve and presented days later to her primary care physician’s office where she was treated with levofloxacin for a suspected urinary tract infection. Her clinical syndrome continued to progress and she developed a widespread rash and generalized edema. She was admitted to the hospital after outpatient laboratory analysis was suggestive of liver and kidney damage. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS syndrome) was suspected in the setting of her fever, rash, elevated liver enzymes, peripheral eosinophilia, and dermatopathological findings. DRESS syndrome is a diagnosis of exclusion and requires a high level of clinical suspicion. The diagnosis was confirmed after review of her history revealed she received two courses of TMP/SMX nearly four weeks prior.

A ten-year retrospective analysis of nocardiosis in a tertiary care center of South-coastal India.

Nocardiosis is an uncommon life-threatening infection caused by Nocardia spp. This study aimed to review the distribution of risk factors, clinical characteristics, microbiological findings, treatment and outcome of patients diagnosed with nocardiosis. This study was a retrospective case record review of all nocardiosis cases that were diagnosed at our tertiary care hospital from January 2008 to December 2019. A total of 48 patients with a mean age of 52.2±16.28 years were included. Out of which forty one (85%) were diagnosed as pulmonary nocardiosis and seven (14.6%) as disseminated disease. Chronic lung disease 25 (52.1%), long term steroid use 22 (45.8%) followed by diabetes mellitus 11 (22.9%) were common predisposing factors. The common symptoms were fever (87.5%), cough (79.2%) and breathlessness (52.1%). The most frequent radiologic finding included consolidation in 38 (79.1%), cavitation with thickened wall in 2 (4.1%), reticulonodular shadows in 2 (4.1%), and unilateral pleural effusion in 5 (10.4%). Nocardia otitidiscaviarum (22.9%) was frequently isolated from cultures. Resistance to trimethoprim-sulfamethoxazole (TMP-SMX) was observed in 21% cases. Mortality was noted in 6 (12.5%) patients and all were with pulmonary involvement. The percentage of death among those with and without pulmonary tuberculosis was 33.3% and 5% respectively. Patients affected by pulmonary nocardiosis with previous history of pulmonary tuberculosis showed significant association with poor outcome (p-value=0.05). In conclusion, nocardiosis mainly affects patients with structural lung disease or immunocompromised hosts with adverse outcome. Awareness of this infection is crucial for a clinician, and any suspicion should lead to make an early diagnosis and choose an appropriate empirical treatment to improve the outcome in this population.

1057. Tebipenem In vitro Activity Against a Collection of Pathogens Responsible for Urinary Tract Infections in the US

1057. Tebipenem <i>In vitro</i> Activity Against a Collection of Pathogens Responsible for Urinary Tract Infections in the US

698. Contemporary Clinical Epidemiology of Pediatric Shigella and Campylobacter Infections in Houston, TX, 2019 and 2020

BackgroundInfections due to Gram-negative, diarrheal pathogens are a significant cause of morbidity in children. Clinical features of pediatric Shigella and Campylobacter infections in urban cities in the United States are not well described.MethodsWe used a retrospective chart review of records (0-18 years of age) from a network of hospitals in Houston, TX. Only patients with Shigella spp. or Campylobacter spp. isolated from clinical samples in 2019 and 2020 were included. Demographic, clinical, and microbiological data were extracted from the medical record. ResultsWe identified a total of 59 and 16 pediatric patients with Shigella spp. and Campylobacter spp. infections, respectively. Hospital admission occurred in 27.1% (16/59) of Shigella and 25% (4/16) of Campylobacter. Length of stay ranged between 1 and 2 days for both pathogens (Table 1). Of cases with available clinical data, Shigella infections were more likely to report fever during their illness compared to Campylobacter (80% versus 45.4%) (Table 2). Seizures were observed in 4 Shigella infected patients. No episodes of Shigella or Campylobacter bacteremia were identified. Among patients with an identified exposure, daycare attendance and contact with individuals experiencing similar symptoms were most common (Table 2). The vast majority of Shigella species were S. sonnei (96.6%) and all Campylobacter were C. jejuni (Table 3). Resistance to trimethoprim-sulfamethoxazole (TMP-SMX) was common (40/55, 72.7%) among Shigella isolates tested. No resistance to fluoroquinolones or third generation cephalosporins in any of the Shigella spp. isolates was observed. Susceptibility testing was not performed in Campylobacter due to lack of isolates. The most frequent antibiotic used was azithromycin (in 73.3% and 75% of patients with Shigella and Campylobacter, respectively). Major complications included urinary tract infection (n=1), rectal prolapse (n=1) and splenomegaly (n=1). ConclusionInfections due to Shigella and Campylobacter were a significant burden among pediatric patients between 2019 and 2020 in Houston, TX. The observed high frequency of resistance to TMP-SMX and emergence of multi-drug resistant Shigella in other countries warrants continued surveillance. Disclosures Anthony R. Flores, MD, MPH, PhD, Nothing to disclose Cesar A. Arias, M.D., MSc, Ph.D., FIDSA, Entasis Therapeutics (Grant/Research Support)MeMed Diagnostics (Grant/Research Support)Merk (Grant/Research Support)