Efficacy of fluoroquinolones as substitutes for ethambutol or rifampin in the treatment of Mycobacterium avium complex pulmonary disease according to radiologic types

Objective: During the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD), ethambutol or rifampin is often discontinued because of adverse events. This study investigated the treatment outcomes when later-generation fluoroquinolones substitute ethambutol or rifampin in MAC-PD treatment based on the radiologic type. Methods: Between 2006 and 2019, patients who initiated standard treatment and whose treatment duration was ≥1 year were retrospectively identified at a tertiary referral center in South Korea, including 178 patients with cavitary disease (fibrocavitary and cavitary nodular bronchiectatic types) and 256 patients with noncavitary nodular bronchiectatic (NC-NB) type. We compared the microbiologic cure at 1 year between the patients who maintained the initial regimen and those who replaced ethambutol or rifampin with fluoroquinolones (moxifloxacin or levofloxacin). Results: The overall microbiologic cure rate of the 178 patients with cavitary disease was 71.3%. Among these, the microbiologic cure rates of the 16 patients who substituted fluoroquinolones for ethambutol were lower than those of the 156 patients who maintained three-drug oral antibiotics with aminoglycoside (37.5% vs. 74.4%, respectively; P = 0.007), which was statistically significant in multivariate analysis. The outcomes of the six patients receiving fluoroquinolones as an alternative to rifampin were similar to that of those continuing the initial regimen. The microbiologic cure rate of the patients with the NC-NB type receiving daily or intermittent oral three-drug therapy was similar regardless of maintaining the initial therapy or replacing ethambutol or rifampin with fluoroquinolones. Conclusions: In cavitary MAC-PD, substituting ethambutol with fluoroquinolones resulted in inferior patient outcomes.

Time to initial highly active antiretroviral therapy discontinuation and its predictors among HIV patients in Felege Hiwot comprehensive specialized hospital: a retrospective cohort study

Background Anti-retroviral therapy regimen discontinuations become a big challenge and cause diminishing the clinical and immunological benefit of treatment in Ethiopia. It reduces both the duration and the chance of viral control due to cross-resistance between different alternative drugs and overlapping toxicity between and within a class of antiretroviral drugs in Ethiopia. However, information’s on the time of initial regimen discontinuation and its predictors are not well studied. Objective This study aimed to assess the time to initial highly active antiretroviral therapy discontinuation and its predictors among HIV patients in Felege Hiwot comprehensive specialized hospital, North West Ethiopia. Method Institution-based retrospective cohort study was conducted among 418 HIV patients who started HAART from January 1, 2014, to December 31, 2019. Data were collected from the patient chart using a data extraction tool. The Kaplan–Meier curve was employed to compare survival rates. Multivariable Cox proportional hazard regression was applied to identify independent predictors of time to initial regimen discontinuation. Result A total of 418 patients on anti-retroviral therapy were followed. Incidence of initial HAART discontinuation was 16.7/100 person year. The median survival time was 3.5 years. Predictors showed association for time to initial HAART discontinuation were taking > 1 ART pills/day (AHR = 4.1, 95% CI 3.0–6.5), baseline CD4 count < 100 cells/mm3 (AHR = 2.6, 95% CI 1.5–4.7), 100–199 cells/mm3 (AHR = 2.2, 95% CI 1.2–4.0), baseline WHO clinical stage IV (AHR = 2.68, 95% CI 1.6–4.3) and stage III (AHR = 2.6, 95% CI 1.4–4.3) and TB infection (AHR = 2.3, 95% CI 1.6–3.5). Conclusion Most of the discontinuation occurred after 1 year of initiation of HAART. Baseline WHO clinical stage, TB infection, baseline CD4 count, and taking > 1 ART pill/day were found predictors of initial HAART regimen discontinuation. Work on early detection of HIV before the disease is advanced and initiation of one ART regimen daily is vital for survival on the initial regimen.

Intrathecal Colistin and Intravenous Fosfomycin as a combination therapy for the treatment of Acinetobacter baumannii Ventriculitis and meningitis: a case report from Nepal

Treatment of central nervous system infection may be troublesome due to multi-drug resistance. Colistin is less successful as a treatment option due to poor CNS penetration when used intravenously. We present the successful management of a case with ventriculitis and meningitis due to MDR Acinetobacter baumannii species with the combined intraventricular administration of colistin and IV fosfomycin after the initial regimen of colistin given alone through both IVT and IV routes had failed.

"Ideal" PTH in ESA-Resistant Anemia

Background: Anemia is a nearly universal complication of End Stage Renal Disease (ESRD). Erythropoiesis-stimulating agents (ESAs) have greatly decreased transfusion dependence in the anemia of ESRD. In some cases, ESAs are not effective, indicating ESA-resistance. ESA-resistant anemia is not well characterized and can be difficult to manage. Among the most frequent causes of ESA-resistant anemia is secondary hyperparathyroidism (SHP), which can induce bone marrow remodeling and fibrosis. Treatment protocols in SHP are centered on goal calcium, phosphorus and parathyroid hormone (PTH) levels and not the biologic consequences of high PTH. The hematologic insults secondary to SHP are rarely addressed. Instead, it is common to simply increase ESA dosing, rather than address the cause of ESA-resistance. In this retrospective review, we describe a cohort of patients with ESRD and SHP and highlight in detail one patient with reversible bone marrow changes and transfusion-dependent anemia, as well as descriptive and laboratory findings of bone marrow changes in patients with anemia and ESRD referred to our center. Methods: Using the EMR, the patient's data including demographics, progress notes, laboratory values, and bone marrow findings were extracted. Subsequently, the EMR was interrogated to reveal all patients with anemia and ESRD, who had undergone a bone marrow biopsy at out center over a ten year period from 2010 to 2020, revealing 64 patients. Data including demographics, laboratory values, bone marrow findings, and medications were extracted. Data was presented descriptively. Results: A 67-year-old male with ESRD secondary to hypertension and type 2 diabetes was referred to our Hematology clinic for anemia of ESRD. He was receiving Epoetin 20,000 IU three times weekly but was still transfusion-dependent to maintain a hemoglobin of 6.3 g/dL, with a concomitant PTH of 400.5 pg/mL. Calcium and phosphorus were normal and thus his SHP was not aggressively managed. Bone marrow biopsy revealed focal areas of bone marrow remodeling and reticulin fibrosis. Fluorescence in situ hybridization studies for myelodysplastic syndrome were negative, as were thyroid studies, serum protein electrophoresis, and free light chain ratio. In conjunction with his nephrologist, treatment of his SHP was optimized. His initial regimen was calcitriol 0.25 mcg once daily and calcium acetate 667 mg three times daily. Subsequently, cinacalcet 30 mg twice daily was added and calcium acetate was replaced with sevelamer 1600 mg three times daily. Following these changes, his hemoglobin remained stable in the range of 8-9 g/dL. He was no longer transfusion-dependent, despite only a modest reduction in PTH to 311.2 pg/mL. Repeat bone marrow biopsy revealed no bone marrow remodeling or reticulin fibrosis. Bone marrow findings for all patients referred to our clinic with ESRD and anemia are summarized in Table 1. The range of PTH for patients with bony remodeling was 183-16161.9 pg/mL versus 90.8-3283 pg/mL for those without bony remodeling. The range of PTH for patients with fibrotic changes was 183-2487 pg/mL versus 90.8-16161.9 pg/mL for those without fibrotic changes. ESA dosing varied among the patients. Conclusion: SHP is an increasingly identifiable cause of ESA-resistant anemia, as demonstrated by the reversal of transfusion dependence in our patient once SHP was more adequately treated. The degree of reversible ESA-resistant anemia and transfusion dependence in the setting of a PTH elevation to 400.5 in this case is surprising. The great variability in PTH levels of patients both with and without bone marrow changes presented here indicates the relationship between SHP and anemia is intricate. A single target level for the whole dialysis population is not appropriate; neither is targeting only and the same goal calcium, phosphorus, and PTH levels for the whole dialysis population either. Based on the findings of our institutional cohort, we suggest that it is justified to deviate from "on-size-fits-all" protocols and attempt a trial of aggressive management of SHP in patients with difficult to manage ESA-resistant anemia with what is considered only modest PTH elevation. Figure 1 Figure 1. Disclosures Moe: Allena Pharmaceutical: Consultancy; Janssen: Consultancy; Alnylum: Consultancy; DIcerna: Consultancy; Tricida: Consultancy.

Antibiotic De-escalation Experience in the Setting of Emergency Department: A Retrospective, Observational Study

Background: Antimicrobial de-escalation (ADE) is a part of antimicrobial stewardship strategies aiming to minimize unnecessary or inappropriate antibiotic exposure to decrease the rate of antimicrobial resistance. Information regarding the effectiveness and safety of ADE in the setting of emergency medicine wards (EMW) is lacking. Methods: Adult patients admitted to EMW and receiving empiric antimicrobial treatment were retrospectively studied. The primary outcome was the rate and timing of ADE. Secondary outcomes included factors associated with early ADE, length of stay, and in-hospital mortality. Results: A total of 336 patients were studied. An initial regimen combining two agents was prescribed in 54.8%. Ureidopenicillins and carbapenems were the most frequently empiric treatment prescribed (25.1% and 13.6%). The rate of the appropriateness of prescribing was 58.3%. De-escalation was performed in 111 (33%) patients. Patients received a successful de-escalation on day 2 (21%), 3 (23%), and 5 (56%). The overall in-hospital mortality was 21%, and it was significantly lower among the de-escalation group than the continuation group (16% vs 25% p = 0.003). In multivariate analysis, de-escalation strategies as well as appropriate empiric and targeted therapy were associated with reduced mortality. Conclusions: ADE appears safe and effective in the setting of EMWs despite that further research is warranted to confirm these findings.

SITUATION USING CARBAPENEM

Objective: To survey the use of carbapenem antibiotics at An Sinh General Hospital. Subjects and methods: retrospective descriptive study on 100 medical records of patients being treated in departments of An Sinh General Hospital from June 1st, 2020 to December 31st, 2020. Results: The carbapenem antibiotic used at An Sinh General Hospital mainly indicated for the treatment of pneumonia accounted for the highest percentage with 53.3%. There were 100% of strains of Haemophilus influenzae; Rhizobium radiobacter; Proteus. cp; Streptococcus mitis, which was also sensitive to carbapenem. 100% strains of Stenotrophomonas maltophilia bacteria was resistant to meropenem; 01 strain of Burkhorderia vietnamiensis was isolated against imipenem; 2 of 3 strains of Staphylococcus aereus isolated were resistant to meropenem. Carbapenem was mainly used in combination regimens. The proportion of the combination in the initial regimen was 100%. The rate of combination of 3 antibiotics was 22.7%. In the replaceable regimen, the combination rate was 82.2%. Conclusion: The carbapenem group was indicated for the treatment of pneumonia. Strains of the bacteria Haemophilus influenzae; Rhizobium radiobacter; Proteus. cp; Streptococcus mitis was also sensitive to carbapenem. Bacteria strains Stenotrophomonas maltophilia, Burkhorderia vietnamiensis and Staphylococcus aereus were resistant to meropenem. Carbapenem was mainly used in combination regimens.

1328. Vancomycin exposure and utilization following implementation of an AUC-guided monitoring guideline in children

Background The 2009 guideline for vancomycin (VAN) monitoring recommended trough (TR) of 15-20 mg/L to correlate with AUC/MIC ≥ 400. Studies have suggested attainment of target AUC/MIC ratio with TR 7-11 mg/L in most children. Prior to 2018, TR 15-20 mg/L was the primary target for VAN therapeutic monitoring at CHOC Children’s. Beginning in 2018, a clinical guideline was implemented which recommend targeting AUC/MIC of 400-600 or TR of 7-15 mg/L. Our objectives are to evaluate differences in VAN utilization, exposure, nephrotoxicity and cost savings between pre (Pre-guideline, pG) and post implementation (Post-guideline, PG) of a VAN monitoring guideline at CHOC Children’s. Methods Retrospective chart review of patients prescribed VAN between Jan 2016 – Jun 2017 (pG) and Jan 2018 – Jun 2019 (PG). Primary objectives evaluated differences in pharmacokinetic (PK), AUC and rate of nephrotoxicity in patients 3 months to &lt; 18 years who received VAN ≥ 24 hour with ≥ 1 TR. Secondary objectives assessed differences in overall VAN utilization following guideline implementation. Results Seventy patients were included in the PK analysis, 35 in pG and 35 in the PG group. Median age, weight, gender, baseline creatinine, concurrent nephrotoxic agents were similar. There were no differences in duration of therapy or starting doses (mg/kg/day) between the two groups. The highest daily dose (mg/kg) and AUC (mg*h/L) attained was significantly higher in pG compared to PG group (74.9 vs. 59.9, p = 0.002 and 647 vs. 469, p &lt; 0.0001), respectively. Changes in AUC from the initial regimen to the highest adjusted regimen was also higher in pG group (532 vs. 647, p = 0.0008) while there was no difference in PG group (459 vs. 469, p = 0.647). More patients experienced nephrotoxicity in pG compared to PG (11.4% (4/35) vs. 0 (0/35), p = 0.039). Logistic regression analysis identified AUC 800-900 as a significant risk for nephrotoxicity. Compared to pG, PG resulted in a net reduction in VAN utilization of 19.7 DOT per 1000 patient days, savings of $100,150 and 738 fewer levels drawn. Conclusion In line with the 2020 consensus guideline recommendation for AUC-based VAN monitoring, our study found AUC-guided VAN monitoring in children resulted in less exposure, utilization, and nephrotoxicity. Disclosures All Authors: No reported disclosures

Effectiveness and safety of first-line antiretroviral regimens in clinical practice: a multicentre cohort study

Objectives We compared 48 week effectiveness and safety of first-line antiretroviral regimens. Methods We analysed HIV treatment-naive adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) starting the most commonly used antiretroviral regimens from 2014 to 2018. We used multivariable regression models to assess the impact of initial regimen on: (i) viral suppression (VS) (viral load &lt;50 copies/mL); (ii) change in CD4 cell count; (iii) CD4/CD8 normalization (&gt;0.4 and &gt;1); (iv) CD4 percentage normalization (&gt;29%); (v) multiple T-cell marker recovery (MTMR: CD4 &gt; 500 cells/mm3 plus CD4 percentage &gt;29% plus CD4/CD8 &gt; 1); (vi) lipid, creatinine and transaminase changes; and (vii) discontinuations due to adverse events (AE). Results Among 3945 individuals analysed, the most frequently prescribed regimens were ABC/3TC/DTG (34.0%), TAF/FTC/EVG/CBT (17.2%), TDF/FTC + DTG (11.9%), TDF/FTC/EVG/CBT (11.7%), TDF/FTC/RPV (11.5%), TDF/FTC + bDRV (8.3%) and TDF/FTC + RAL (5.3%). At 48 weeks, 89.7% of individuals achieved VS with no significant differences by initial regimen. CD4 mean increase was 257.8 (249.3; 266.2) cells/mm3, and it was lower with TAF/FTC/EVG/CBT and TDF/FTC/RPV compared with ABC/3TC/DTG. CD4 percentage normalization was less likely with TAF/FTC/EVG/CBT, and MTMR was less likely with TAF/FTC/EVG/CBT and TDF/FTC + RAL. The proportion of discontinuations due to AE was higher with TDF/FTC + bDRV (9.7%), followed by TDF/FTC/EVG/CBT (9.5%) and TDF/FTC + DTG (7.9%). Compared with ABC/3TC/DTG, cholesterol and LDL mean increases were higher with TAF/FTC/EVG/CBT and lower with TDF/FTC + DTG, TDF/FTC/RPV and TDF/FTC + RAL. Higher mean increases in triglycerides were significantly associated with TAF/FTC/EVG/CBT. Regimens containing DTG showed higher creatinine increases. Conclusions The significantly greater immunological response and safety of some combinations may be useful for making decisions when initiating treatment.

Combination of Direct Antiviral Therapy in Hepatitis C Patients, Population of Karachi

Background: Pakistan has approximately eight million Hepatitis C Virus infected patients. Initial regimen of interferon-based along with ribavirin showed SVR (Sustained Virological Response Rate) of up to 50%. The new standard ‘DAA therapy’ with improved response rates raised SVR rates to as high as 90%. This study was conducted to determine the outcome of the novel combined DAA regimen in hepatitis C infected patients in Karachi, Pakistan. Methods: Fifty patients with infected with HCV were participants of this study. They were from the gastroenterology ward and OPD Jinnah Medical Hospital (JMCH), Karachi. Initial investigations included blood samples for complete picture (CP) and liver function test (LFT). After performing qualitative Polymerase Chain Reaction (PCR), patients diagnosed with hepatitis C (pangenotypes) were prescribed direct antiviral therapy. Results: Out of total fifty patients diagnosed with HCV infection, forty compensated patients of hepatitis C were prescribed combination of Sofosbuvir and Velpatasvir, of these thirty five patients (100%) had shown to be PCR negative after three months of therapy and negative PCR after 3 months follow-up, five patients were loss to follow. Ten patients decompensated (with ascites, cirrhosis or hepatic encephalopathy) were prescribed Sofosbuvir + Velpatasvir along with ribavirin, seven (100%) had shown to be PCR negative and three were loss to follow. Conclusion: Sofosbuvir and Velpatasvir was most effective combination of direct antiviral regimen in treatment of HCV pan-genotype patients, with least adverse-effects and much better outcome in both compensated and decompensated (with ascites and cirrhosis) hepatitis C infected patients.