AbuSaleh, Omar

Abstract We describe early experience with beta-lactam therapeutic drug monitoring (TDM) in a high-volume outpatient parenteral antimicrobial therapy program. In selected patients, TDM informed dose optimization and toxicity mitigation. Illustrative cases highlight feasibility and emerging lessons supporting beta-lactam TDM in outpatient care.

Background: There are limited oral treatment options available for resistant Gram-negative bacterial (GNB) infections. Minocycline, a second-generation tetracycline antibiotic, offers good bioavailability and broad-spectrum coverage that may be an option for GNB infections. Methods: We conducted a retrospective review of minocycline susceptibility testing performed on GNB isolates at the Mayo Clinic reference lab between 2013 and 2022. Minocycline susceptibility was evaluated with a focus on difficult-to-treat organisms and relevant anatomic source. Organisms included resistant isolates of Escherichia coli and Klebsiella pneumoniae ; high-risk ampC-derepressors, including Citrobacter freundii, Enterobacter cloacae, and K. aerogenes; and clinically challenging non-Enterobacterales, Acinetobacter species, Achromobacter species, and Stenotrophomonas maltophilia . Results: Of 217,206 GNB isolates, 18,148 Enterobacterales (EB) and 8,190 non- Enterobacter isolates were tested for minocycline susceptibility. Of these, 80% of all EB and 92% of non-EB isolates were susceptible. Among E. coli isolates with ceftriaxone, ciprofloxacin, meropenem, or multidrug resistance, minocycline susceptibility was 78%, 76%, 70%, and 70.9%, respectively. Among the K. pneumoniae isolates with ceftriaxone, ciprofloxacin, meropenem, or multidrug resistance, minocycline susceptibility was 46%, 38%, 37%, and 39.3%, respectively. 85% of C. freundii , 81% of E. cloacae, and 85% of K. aerogenes isolates were susceptible to Minocycline. 83.5% of Achromobacter species isolates, 66% of Acinetobacter species isolates, and 99.1% of S. maltophilia isolates were susceptible. Conclusions: Our study reports the largest collection of minocycline susceptibility findings in GNB. Minocycline showed in vitro activity against many difficult-to-treat GNB isolates, including ceftriaxone- and multidrug-resistant E. coli and some K. pneumoniae isolates, common Amp-C-producing species, and non-fermenting GNB, including Stenotrophomonas , Acinetobacter , and Achromobacter .

AbstractHistoplasma capsulatum is an endemic fungus that most oftenly causes a self‐limiting illness but can result in severe infections in immunocompromised patients including pulmonary or extra‐pulmonary disease. Rarely it can also cause a chronic progressive infection of the larynx. Herein, we report a case of laryngeal histoplasmosis in a kidney transplant patient who presented with progressive symptoms of several weeks of hoarseness, dysphagia and odynophagia. Laryngoscopic examination revealed thick plaques in the oropharynx with surrounding hyper‐erythema and histopathology showed numerous intracellular yeasts forms consistent with H capsulatum. Patient was initiated on treatment with itraconazole. Infection of the larynx due to H capsulatum is highly uncommon and therefore can result in an inappropriate or delayed diagnosis. A review of literature showed four previously reported cases of laryngeal histoplasmosis in patients with solid organ transplant. This is the first case series of laryngeal histoplasmosis in transplant recipients.

Abstract Background Stenotrophomonas maltophilia is a hospital acquired infection that is associated with high morbidity and mortality. There has been a reported rise in S. maltophilia infections, presumed secondary to the increase in the population at risk. Methods We retrospectively reviewed all hospitalized adult patients in Mayo Clinic, MN with S. maltophilia bacteremia from January 2008 through January 2018. We analyzed patient population and described patients at risk, sources of infection, and changes in antimicrobial susceptibility profile. Results A total of 94 patients were analyzed, including 52 males, median age of 56 (46–65.75 IQR). The population included 60 infections in those with malignancies and 30 infections in transplant recipients. At presentation, 58 (61.7%) were febrile, while 54 (58.1%) presented with hemodynamic instability. Majority (70.2%) received broad-spectrum antimicrobials within 2 weeks of presentation. The most common source was catheter associated infection (n = 60), 15 cases were secondary to gastrointestinal, and 9 due to a pulmonary source. Almost half, 46 (48.9%) required ICU admission. Two patients were diagnosed with endocarditis. Most isolates, 61(64.9%), were resistant to ceftazidime, 2 (2.2%) resistant to TMP/SMX and 20 (21.5%) were resistant to levofloxacin. Exposure to a quinolone in the 30 days prior to presentation did not impact fluoroquinolone resistance. Five patients were exposed to Trimethoprim/Sulfamethoxazole (TMP/SMX) in the 30 days prior to presentation, which was associated with higher rate of TMP/SMX resistance compared with those without exposure (80% vs. 98.8%, P = 0.004). Treatment options commonly included combination therapy, and TMP/SMX was a primary agent used in the majority, 59 (62.8%). All-cause in-hospital mortality was 26.6%. All-cause mortality was lower for line associated infections (16.67%) vs. other sources (44.12%) with P = 0.0038. Conclusion S. maltophilia bacteremia should be considered in hospitalized patients with recent use of broad-spectrum antibiotics. Although TMP/SMX continues to have reliable activity, use of empiric ceftazidime pending susceptibility testing should be avoided as trend toward increasing resistance is noted. We noted a drop in TMP/SMX susceptibility in those with recent reported TMP/SMX use. Disclosures All authors: No reported disclosures.

Abstract Background Fluoroquinolones (FQ) are among the most commonly prescribed antibiotics. Nephrotoxicity related to FQ use is infrequently reported and the mechanism of renal injury is incompletely elucidated. We describe clinical manifestations and outcome of patients with biopsy proven acute interstitial nephritis (AIN) associated with FQ use at our institution. Methods We conducted a retrospective review of biopsy-proven AIN attributed to FQ use at Mayo Clinic Rochester from 1993 to 2016. Cases were reviewed by a renal pathologist and attributed to FQ use by an expert nephrologist. We also reviewed and summarized all published case reports of biopsy proven AIN that were attributed to FQ use. Results We identified 24 patients with FQ-related biopsy-proven AIN. The most commonly used FQ was ciprofloxacin (71%) with median antibiotic treatment duration of 7 days (Figure 1). The median duration between starting FQ and the diagnosis of AIN was 8.5 (IQR: 17). Common clinical manifestations included fever (50%), flank pain (8%), and skin rash (21%). However, 17% of the patients were asymptomatic at the time of diagnosis (Figure 2). Majority (58%) of the patients recovered following discontinuation of antibiotics and returned to baseline renal function at a median of 20.5 (IQR: 15.5). Six patients required temporary hemodialysis and 9 patients received steroids. Conclusion Onset of FQ-related AIN can be delayed and a high index of suspicion is needed by physicians prescribing these agents. Overall outcomes are favorable with recovery to baseline renal function within 3 weeks of discontinuing the offending drug. Disclosures All authors: No reported disclosures.

A 61-year-old man with relapsing chronic lymphocytic leukaemia, status post allogeneic stem cell transplant and multiple chemotherapy regimens presented to the emergency room after suffering a grand mal seizure. His evaluation revealed a 1.5–2 cm ring-enhancing left temporal lobe brain lesion on the CT scan. This brain lesion was resected and the histopathology revealed an invasive fungal organism resembling mucormycosis. Amplification and sequencing of the 28S ribosomal RNA gene identified the organism as Rhizomucor pusillus. The patient was treated with liposomal amphotericin B 5 mg/kg every 24 hours for 4 weeks, and then was transitioned to oral posaconazole. Serial brain imaging at 1 and 3 months, while on therapy, showed significant improvement.