Anaphylaxis Due to Remdesivir.

In December 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Wuhan, China and found to cause acute respiratory symptoms and pneumonia.1….

Empiric versus culture-based antibiotic therapy for UTIs in menopausal women.

PURPOSE: To assess the benefits and risks associated with empiric prescription of antibiotic therapy for treatment of a urinary tract infection (UTI). METHODS: Following IRB approval menopausal women presenting with a symptomatic UTI to a single urology clinic were prospectively assigned to one of the two treatment groups based on day of presentation: culture-based treatment (CB) (Monday, Tuesday, Wednesday) or empiric treatment (ET) (Thursday, Friday) and started on nitrofurantoin (NF) pending culture results. Both groups were contacted at 7 and 14 days following treatment. Side effects and answers to a standardized questionnaire (UTISA) were recorded. Success was defined as a total UTISA score < 3. Any NF retreatment, use of another antibiotic therapy, or extension of the original antibiotic course was considered treatment failures. RESULTS: From July 2020 to March 2022, 65 women with 80 UTI events were included in the study, with CB treatment used for 60 UTIs and ET used for 23 UTIs. At 7 days after start of treatment, questionnaire failure rate was 44% (20/45) for the CB group and 16% (3/19) for the ET group (P = 0.076). At 14 days following start of treatment, questionnaire failure rate was 31% (13/42) for the CB group and 17% (3/18) for the ET group (P = 0.3). In the ET group, 11% of cultures were found to be resistant to NF. CONCLUSION: Outcomes for the empiric treatment of uncomplicated UTI with NF at both 7 and 14 days are not significantly different than outcomes with culture-based treatment.

Adverse effects of chronic nitrofurantoin therapy in women with recurrent urinary tract infections in an outpatient setting.

PURPOSE: To review the frequency of adverse events reported with nitrofurantoin (NF) in perimenopausal and menopausal women on prolonged daily prophylaxis in an outpatient setting. METHODS: Electronic medical records of women aged 50-95 prescribed NF by 2 primary urology providers for at least 3 consecutive months from 2006 to 2018 were retrospectively reviewed. Demographics, reason for the initiation, dose and duration of therapy, explanation of therapy interruptions, occurrence of adverse events, comorbid conditions, and relevant lab and imaging results were recorded. The number of months on prolonged therapy were summed. RESULTS: Of the 221 patients included, 167 (77%) were prescribed 100 mg of NF daily with a mean duration of therapy of 1.5 years. The most common indication for therapy was recurrent urinary tract infection prophylaxis. Breakthrough urinary tract infections developed in 88 (40%) patients on prolonged NF therapy but only 10 were not restarted on NF. Four patients (1.8%) were determined to have pulmonary adverse events and 1 (0.4%) developed elevated liver function tests. CONCLUSION: In peri-menopausal and menopausal women, the risks and benefits of chronic NF therapy should be weighed by the clinician and patient prior to prescribing long term NF. Patients must be educated about the potential NF toxicities and clinically monitored for signs and symptoms of potential adverse events while on chronic NF therapy.

Minimal Cerebrospinal Fluid Concentration of Miltefosine despite Therapeutic Plasma Levels during the Treatment of Amebic Encephalitis.

Miltefosine is an alkylphosphocholine compound that is used primarily for treatment of leishmaniasis and demonstrates in vitro and in vivo antiamebic activity against Acanthamoeba species. Recommendations for treatment of amebic encephalitis generally include miltefosine therapy. Data indicate that treatment with an amebicidal concentration of at least 16 µg/ml of miltefosine is required for most Acanthamoeba species. Although there is a high level of mortality associated with amebic encephalitis, a paucity of data regarding miltefosine levels in plasma and cerebrospinal fluid in vivo exists in the literature. We found that despite aggressive dosing (oral miltefosine 50 mg every 6 h) and therapeutic plasma levels, the miltefosine concentration in cerebrospinal fluid was negligible in a patient with AIDS and Acanthamoeba encephalitis.

Successful Treatment of Persistent Burkholderia cepacia Complex Bacteremia with Ceftazidime-Avibactam.

We report our clinical experience treating a 2-month-old infant with congenital diaphragmatic hernia who experienced prolonged bacteremia with Burkholderia cepacia complex (Bcc) despite conventional antibiotic therapy and appropriate source control measures. The infection resolved after initiation of ceftazidime-avibactam. Whole-genome sequencing revealed that the isolate most closely resembled B. contaminans and identified the mechanism of resistance that likely contributed to clinical cure with this agent. Ceftazidime-avibactam should be considered salvage therapy for Bcc infections if other treatment options have been exhausted.

Letermovir successfully used for secondary prophylaxis in a heart transplant recipient with ganciclovir-resistant cytomegalovirus syndrome (UL97 mutation).

Letermovir was approved by the Food and Drug Administration (FDA) in November 2017 for use in adult cytomegalovirus (CMV)-seropositive allogeneic stem cell transplant (SCT) recipients for primary prophylaxis of CMV infection and disease. We report off-label use of letermovir for secondary prophylaxis of genotype-confirmed ganciclovir-resistant cytomegalovirus (CMV) syndrome (UL 97 mutation [C603W]) in a heart transplant recipient initially treated with intravenous cidofovir followed by foscarnet, both discontinued due to unacceptable toxicities.

What's in a name? The heterogeneous clinical spectrum and prognostic factors in a cohort of adults with hemophagocytic lymphohistiocytosis.

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) in adults is rare but frequently fatal. Diagnosis is often delayed and treatment approaches vary significantly in contrast to the protocol-driven approach typically used in pediatric HLH. To improve care of these complex patients, this study retrospectively examined the prevalence, clinical characteristics, therapies and outcomes of adult HLH patients at two large tertiary care centers. METHODS: Adult patients with HLH confirmed by retrospective review of electronic medical records using HLH2004 criteria during admissions to the University of Texas Southwestern and Parkland Memorial Hospitals between June 2007 and June 2017 were studied. RESULTS: Of 31 patients included, 67.7% were male with mean age of 46 years. Average time from admission to diagnosis was 10.5 days. 48% of patients had malignancy, with T-cell lymphoma being most common. Infections were seen in 70%. Autoimmune disorders were found in 9.6%. In total, 13 patients survived (44.8%). Median survival was 8 months with increased mortality in malignancy-associated HLH (median 0.56 months versus 36.5 months, p < 0.001). T-cell lymphoma carried a worse prognosis than other malignancies. Central nervous system disease, hypoalbuminemia, elevated bilirubin, elevated soluble interleukin 2 receptor, and elevated lactate dehydrogenase, were also associated with poor survival. Treatment varied significantly. No individual treatment improved survival. CONCLUSION: This study corroborates prior limited data in adult HLH patients regarding poor survival, particularly in malignancy-associated HLH. Earlier recognition of this disease and a multidisciplinary approach to streamline diagnosis and optimize treatment are needed to improve outcomes in adult HLH patients.

Combination eravacycline therapy for ventilator-associated pneumonia due to carbapenem-resistant Acinetobacter baumannii in patients with COVID-19: A case series.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia is associated with poor clinical outcomes and increased mortality. Clinical data regarding the optimal treatment of CRAB is limited, and combination therapy is often preferred. Eravacycline has demonstrated in-vitro activity against A. baumannii and has been considered for the treatment of pulmonary infections caused by CRAB. OBJECTIVE: The objective of this case series was to describe clinical outcomes associated with eravacycline when utilized as part of a combination regimen for the treatment of CRAB pneumonia at a county hospital. METHODS: A retrospective chart review was conducted from April 1, 2020, to October 1, 2020, which included hospitalized patients ≥18 years of age, diagnosed with coronavirus disease 2019 (COVID-19), with a sputum culture positive for CRAB, and receipt of at least one dose of eravacycline. The primary outcome studied was clinical resolution of CRAB pneumonia. A key secondary outcome was microbiological resolution. RESULTS: A total of 24 patients received combination eravacycline therapy for a median of 10.5 days. Overall, 17 (71%) patients demonstrated clinical resolution of CRAB pneumonia. Repeat sputum cultures post-treatment were collected in 17 (71%) patients, of which 12 (71%) achieved microbiological resolution. No adverse events attributable to eravacycline were identified. CONCLUSION: With limited viable salvage treatment options, combination eravacycline therapy showed favorable microbiological and clinical outcomes in patients with CRAB pneumonia. In light of this, eravacycline could be considered as a potential treatment option when designing CRAB pneumonia salvage therapy regimens.

Impact of Urine Culture Reflex Policy Implementation in a Large County Hospital Inpatient Rehabilitation Unit-A Pilot Study.

OBJECTIVE: To promote antimicrobial stewardship, many institutions have implemented a policy of reflexing to a urine culture based on a positive urinalysis result. The rehabilitation patient population, including individuals with brain and spinal cord injuries, may have atypical presentations of urinary tract infections. The study objective is to determine the effects of implementing a urine culture reflex policy in this specific patient population. DESIGN: In an inpatient rehabilitation unit, 348 urinalyses were analyzed from August 2019 to June 2021. Urinalysis with greater than or equal to 10 white blood cells per high power field was automatically reflexed to a urine culture in this prospective study. Primary outcome was return to acute care related to urinary tract infection. Secondary outcomes included adherence to reflex protocol, antibiotic utilization and appropriateness, adverse outcomes related to antibiotic use, and reduction in urine cultures processed and the associated reduction in healthcare costs. RESULTS: There was no statistically significant difference before and after intervention related to the primary outcome. Urine cultures processed were reduced by 58% after intervention. CONCLUSIONS: Urine culture reflex policy is likely an effective intervention to reduce the frequency of urine cultures without significantly affecting the need to transfer patients from inpatient rehabilitation back to the acute care setting.

Robotic simple cystectomy as a last resort for antibiotic-recalcitrant recurrent urinary tract infections in women.

OBJECTIVE: To report a series of women with antibiotic-recalcitrant recurrent urinary tract infections (rUTI) managed with robotic simple cystectomy and ileal conduit urinary diversion. METHODS: Following Institutional Review Board approval, all female patients who underwent robotic cystectomy for rUTI between 2011 and 2021 were identified from a prospectively-maintained internal database at a tertiary care center. Exclusion criteria included interstitial cystitis, neurogenic bladder, urinary tract neoplasm, or congenital abnormality. Electronic medical records were reviewed by an independent researcher. Patients were also administered the Quality of Life Questionnaire-C30. RESULTS: Twenty-four patients met inclusion criteria. Median age was 75 years (range 53-87). Median rUTI duration was 6 (interquartile range [IQR] 2-10) years. Median urinary tract infections count in the 12-month preceding cystectomy was 5 (IQR 3-9). Infections with multidrug resistant organisms were found in 21 patients (88%). The 30-day postoperative complication rate was 79% (19/24), of which 11% were Clavien-Dindo grade ≥III. The main late complication was parastomal hernia, with 17% requiring repair or revision. At a median of 36 months (range 12-61) post-operatively, the median Quality of Life Questionnaire-C30 global health status score was 50 (range 33-83). CONCLUSION: Cystectomy is a last-resort management option for women with severely symptomatic end-stage bladders in the setting of antibiotic-recalcitrant rUTI. Patients should be counseled thoroughly regarding possible acute and long-term postoperative complications. Select patients, managed in high-volume referral centers, can benefit from robotic simple cystectomy with ileal conduit urinary diversion.

Incidence of drug-resistant pathogens in community-acquired pneumonia at a safety net hospital.

The 2019 Infectious Diseases Society of America guideline for the management of community-acquired pneumonia (CAP) emphasizes the need for clinician to understand local epidemiological data to guide selection of appropriate treatment. Currently, the local distribution of causative pathogens and their associated resistance patterns in CAP is unknown. A retrospective observational study was performed of patients admitted to an 870-bed safety net hospital between March 2016 and March 2021 who received a diagnosis of CAP or healthcare-associated pneumonia within the first 48 hours of admission. The primary outcome was the incidence of CAP caused by methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (PsA) as determined by comparing the number of satisfactory sputum cultures or blood cultures with these drug-resistant organisms to the total number of reviewed patients. Secondary outcomes studied included risk factors associated with CAP caused by drug-resistant organisms, utilization of broad-spectrum antibiotics, appropriate antibiotic de-escalation within 72 hours, and treatment duration. In this 220-patient cohort, MRSA or PsA was isolated from three sputum cultures and no blood cultures. The local incidence of drug-resistant pathogens among the analyzed sample of CAP patients was 1.4% (n = 3/220). The overall incidence of CAP caused by MRSA or PsA among admitted patients is low at our safety-net county hospital. Future research is needed to identify local risk factors associated with the development of CAP caused by drug-resistant pathogens.IMPORTANCEThis study investigates the incidence of drug-resistant pathogens including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa among community-acquired pneumonia (CAP) patients at a safety net hospital. Understanding local bacteria resistance patterns when treating CAP is essential and supported by evidence-based guidelines. Our findings empower other clinicians to investigate resistance patterns at their own institutions and identify methods to improve antibiotic use. This has the potential to reduce the unnecessary use of broad-spectrum antibiotic agents and combat the development of antibiotic resistance.

Impact of Respiratory Viral Panel Results on Piperacillin-Tazobactam Use in a Medical Intensive Care Unit: A Single-Center Retrospective Study.

PURPOSE: In critically ill patients with acute respiratory infection, antibiotic stewardship can be challenging given the acuity and complexities of such patients, and the associated high mortality. This study determined the impact of respiratory viral panel (RVP) testing on piperacillin-tazobactam (PT) use in patients admitted to a medical intensive care unit (MICU). METHODS: This retrospective chart review used data from adults admitted to a MICU between January 1, 2017, and January 31, 2018, and with findings from at least one RVP available. FINDINGS: RVP testing was performed on samples from 90 patients admitted to the MICU. RVP was positive in 41% (37/90) of patients, and 53.3% (48/90) received PT during their MICU stay. PT was discontinued in 25.5% (23/90) of patients, 16.2% (6/37) with a positive RVP and 32.1% (17/53) with a negative RVP. Overall mortality was significantly lower in the positive RVP group versus the negative RVP group (odds ratio = 0.28; P = 0.001). In a multivariate Cox proportional hazards model (adjusted for acute kidney injury and culture positivity), the risk for PT discontinuation was significantly less in patients with a positive RVP compared to those with a negative RVP (primary outcome). Overall mortality rate and median length of stay were significantly lower in patients with a positive RVP compared to those in patients with a negative RVP (secondary outcomes). The 30-day hospital readmission rate and the risk for AKI were not significantly different between those with positive versus negative RVP. IMPLICATIONS: Reasons for these observations are currently unclear, but deserve further exploration in future studies. It is hypothesized that the treating providers were concerned about the presence of concurrent bacterial infections along with the diagnosed viral infections given that the patients were critically ill. This suggests that RVP results did not impact PT-prescribing practices in the MICU, and thus that the routine use of RVP solely for guiding antimicrobial-stewardship practices may not be effective.

Little Utility of Fungal Blood Cultures in Surgical and Burn Intensive Care Units.

Critically ill patients are at risk for fungal infections, but there is a paucity of data regarding the clinical utility of dedicated fungal blood cultures to detect such infections. A retrospective review was conducted of patients admitted to the surgical and burn intensive care units at Parkland Memorial Hospital between 1 January 2013 and 31 December 2017 for whom blood cultures (aerobic, anaerobic, and/or fungal cultures) were sent. A total of 1,094 aerobic and anaerobic blood culture sets and 523 fungal blood cultures were sent. Of the aerobic and anaerobic culture sets, 42/1,094 (3.8%) were positive for fungal growth. All fungal species cultured were Candida. Of the fungal blood cultures, 4/523 (0.76%) were positive for growth. Fungal species isolated included Candida albicans, Aspergillus fumigatus, and Histoplasma capsulatum. All 4 patients with positive fungal blood cultures were on empirical antifungal therapy prior to results, and the antifungal regimen was changed for 1 patient based on culture data. The average duration to final fungal culture result was 46 days, while the time to preliminary results varied dramatically. Two of the four patients died prior to fungal culture results, thereby rendering the culture data inconsequential in patient care decisions. This study demonstrates that regular aerobic and anaerobic blood cultures sets are sufficient in detecting the most common causes of fungemia and that results from fungal cultures rarely impact treatment management decisions in patients in surgical and burn intensive care units. There is little clinical utility to routine fungal cultures in this patient population. IMPORTANCE This study demonstrates that regular aerobic and anaerobic blood culture sets are sufficient in detecting the most common causes of fungemia, and thus, sending fungal blood cultures for patients in surgical and burn intensive care units is not a good use of resources.

Fosfomycin Prevents Intravenous Antibiotic Therapy in Women With Recurrent Urinary Tract Infections: A Retrospective Review.

OBJECTIVES: The aim of this study was to evaluate the role of oral fosfomycin to prevent the use of intravenous (IV) antibiotic therapy in women with recurrent urinary tract infection (RUTI) complicated by antibiotic allergies and/or multidrug-resistant organisms. METHODS: After institutional review board approval, a retrospective review of women prescribed fosfomycin for RUTI at our institution was performed. Excluded were patients who did not take fosfomycin. Data collected included demographics, baseline voiding function/urological anatomic abnormalities, need for IV antibiotic therapy for RUTI, RUTI-related surgery, antibiotic allergies, and urine culture results before and after taking fosfomycin. Success was defined as no subsequent IV antibiotic use for RUTI management after fosfomycin within the study follow-up. Secondary outcomes included time to next UTI after fosfomycin, time to next extended-spectrum beta-lactamase UTI, factors predicting failure, urine culture results after fosfomycin, and need for surgical intervention. RESULTS: Between 2013 and 2019, 105 women met study criteria. At a median follow-up (including phone interviews) of 1.7 years (interquartile range, 0.3-5.8) after fosfomycin, the success rate was 74%. Twenty-seven patients had documented sterile urine cultures immediately after fosfomycin. Prior history of hospitalization for UTI and infection with resistant organisms were predictive of failure. After fosfomycin, 25 women underwent bladder electrofulguration, and 3 required cystectomy. CONCLUSIONS: Fosfomycin reduced the rate of IV antibiotic therapy in the management of RUTI in women with multidrug-resistant organisms and/or antibiotic allergies. Fosfomycin was less effective in those with prior hospitalization for UTI or infection with resistant organisms.

A retrospective review of oral cephalosporins versus fluoroquinolones for the treatment of pyelonephritis.

BACKGROUND: The current Infectious Diseases Society of America guidelines for the treatment of acute uncomplicated pyelonephritis (AUP) advise caution when using oral beta-lactams due to concern for potentially inferior efficacy compared to fluoroquinolones (FQs) and trimethoprim-sulfamethoxazole; however, studies specifically evaluating the efficacy of oral cephalosporins (CPs) in AUP are limited. OBJECTIVE: To assess the safety and efficacy of oral CPs versus FQs for the treatment of AUP. DESIGN, SETTING AND PARTICIPANTS: This is a retrospective, chart review study conducted at a single-center, tertiary care hospital. MEASUREMENTS: The primary endpoint was treatment failure within 30 days, defined as a change in antibiotic or return to ED or clinic due to persistent symptoms. Secondary endpoints included adverse drug reactions (ADRs) and C. difficile infection (CDI) within 30 days. RESULTS: Of the 343 patients included in the study, treatment failure occurred in 54/338 (16.0%) patients and was similar between oral CPs and FQs (35/229 [15.3%] vs. 19/109 [17.4%]). A higher percentage of treatment failures were observed for third generation (3GC) and first generation (1GC) CPs compared to second generation CPs (2GC) (3GC: 15/65 [23.4%]; 1GC: 11/49 [22.4%]; 2GC: 9/115 [7.8%]). Documented ADRs were low (6/343 [1.7%]) and no cases of CDI were documented. CONCLUSIONS: Oral CPs appear to be as safe and effective as FQs for the treatment of AUP. Fewer treatment failures were noted with 2GCs as compared to 3GCs and 1GCs.

Bartonella quintana Infection Manifesting as Leucocytoclastic Vasculitis Rash.

We present the first case described in the literature of leucocytoclastic vasculitis due to Bartonella quintana infection. A 73-year-old woman presented to the hospital with persistent fevers, retro-orbital headache, generalized weakness, and left lower thigh pain for 1 week. She was found to have truncal and proximal lower extremity papules and small plaques. Serology revealed Bartonella quintana immunoglobulin M (IgM) titer of 1:256 with undetectable Bartonella quintana immunoglobulin G (IgG) and undetectable Bartonella henselae IgG and IgM. Skin biopsy of an abdominal lesion revealed fibrinoid necrosis of vessel walls in the superficial and mid-dermis consistent with leucocytoclastic vasculitis. Doxycycline 100 mg orally twice daily was initiated, after which she had defervescence within 36 hours and rapid improvement of other presenting symptoms.

Improved Antibiotic Prescribing Practices for Respiratory Infections Through Use of Computerized Order Sets and Educational Sessions in Pediatric Clinics.

BACKGROUND: Computerized clinical decision support systems (CDSS) have shown promising effectiveness in improving outpatient antibiotic prescribing. METHODS: We developed an intervention in the form of EPIC (Verona, WI, USA) order sets comprised of outpatient treatment pathways for 3 pediatric bacterial acute respiratory infections (ARIs) coupled with educational sessions. Four pediatric clinics were randomized into intervention and control arms over pre- and postimplementation study periods. In the intervention clinics, education was provided in between the 2 study periods and EPIC order sets became available at the beginning of the postimplementation period. The primary end point was the percentage of first-line antibiotic prescribing, and the secondary end points included antibiotic duration and antibiotic prescription modification within 14 days. RESULTS: A total of 2690 antibiotic prescriptions were included. During the pre-implementation phase, there was no difference in first-line antibiotic prescribing (74.9% vs 77.7%; P = .211) or antibiotic duration (9.69 ± 0.96 days vs 9.63 ± 1.07 days; P > .999) between the study arms. Following implementation, the intervention clinics had a higher percentage of first-line antibiotic prescribing (83.1% vs 77.7%; P = .024) and shorter antibiotic duration (9.28 ± 1.56 days vs 9.79 ± 0.75 days; P < .001) compared with the control clinics. The percentage of modified antibiotics was small in all clinics (1.1%-1.6%) and did not differ before and after the intervention (for all statistical comparisons, P ≤ .354). CONCLUSIONS: A computerized CDSS involving treatment pathways in the form of order sets coupled with educational sessions was associated with a higher percentage of first-line antibiotic prescribing and shorter antibiotic duration for the outpatient treatment of pediatric bacterial ARIs.

Minimal impact of selective susceptibility reporting on the use of piperacillin-tazobactam for Escherichia coli and Klebsiella bacteremia.

Selective cascade reporting of antibiotic susceptibilities did not have a significant impact on de-escalation from piperacillin-tazobactam (PT), duration of PT use, length of stay, or rates of acute kidney injury and Clostridioides difficile infection in patients with positive monomicrobial blood cultures with either Escherichia coli or Klebsiella spp.