Prolonged Duration Of Therapy Research Articles

Utilization of broad- versus narrow-spectrum antibiotics for the treatment of outpatient community-acquired pneumonia among adults in the United States.

To characterize antibiotic utilization for outpatient community-acquired pneumonia (CAP) in the United States. We conducted a cohort study among adults 18-64 years diagnosed with outpatient CAP and a same-day guideline-recommended oral antibiotic fill in the MarketScan® Commercial Database (2008-2019). We excluded patients coded for chronic lung disease or immunosuppressive disease; recent hospitalization or frequent healthcare exposure (e.g., home wound care, patients with cancer); recent antibiotics; or recent infection. We characterized utilization of broad-spectrum antibiotics (respiratory fluoroquinolone, β-lactam + macrolide, β-lactam + doxycycline) versus narrow-spectrum antibiotics (macrolide, doxycycline) overall and by patient- and provider-level characteristics. Per 2007 IDSA/ATS guidelines, we stratified analyses by otherwise healthy patients and patients with comorbidities (coded for diabetes; chronic heart, liver, or renal disease; etc.). Among 263 914 otherwise healthy CAP patients, 35% received broad-spectrum antibiotics (not recommended); among 37 161 CAP patients with comorbidities, 44% received broad-spectrum antibiotics (recommended). Ten-day antibiotic treatment durations were the most common for all antibiotic classes except macrolides. From 2008 to 2019, broad-spectrum antibiotic use substantially decreased from 45% to 19% in otherwise healthy patients (average annual percentage change [AAPC], -7.5% [95% CI -9.2%, -5.9%]), and from 55% to 29% in patients with comorbidities (AAPC, -5.8% [95% CI -8.8%, -2.6%]). In subgroup analyses, broad-spectrum antibiotic use varied by age, geographic region, provider specialty, and provider location. Real-world use of broad-spectrum antibiotics for outpatient CAP declined over time but remained common, irrespective of comorbidity status. Prolonged duration of therapy was common. Antimicrobial stewardship is needed to aid selection according to comorbidity status and to promote shorter courses.

Reaching high-hanging fruit in antimicrobial stewardship: a hospital-based intervention to withdraw inappropriately prescribed antimicrobials.

Antimicrobial stewardship programs (ASPs) are responsible for addressing unnecessary antimicrobial use. We describe our experience with a unique intervention to withdraw unnecessary antimicrobials. Design, Setting, Participants: descriptive case series of adult inpatients at a single academic medical center, December 2021 to December 2022; Intervention: hospital-wide policy allowing ASP to discontinue inappropriate antimicrobials in select cases not resolved by prospective audit and feedback; Measures: count, date, and generic names of antimicrobials prescribed; reason for antimicrobial withdrawal (prolonged duration, no evidence of infection, or other); withdrawals by inpatient service (surgical or medical); time from antimicrobial start date to withdrawal intervention; days of therapy (DOT) saved; "nudge effect" defined as the prescribing team self-discontinuing withdrawn antimicrobial within 24 hours of withdrawal notice; appeals to withdrawals; ordering of alternative antimicrobials following withdrawal; incident infections, readmission, in-hospital mortality within 30 days of withdrawal intervention. There were 54 antimicrobials withdrawn among 36 unique patients during the study period; piperacillin-tazobactam followed by vancomycin were the most frequently withdrawn agents; prolonged duration of therapy or prophylaxis followed by no evidence of infection were the most common reasons for withdrawal; withdrawals occurred most often on surgical services; an estimated 236 DOT (27.2 DOT per 100 patient-days) were saved; 32% of withdrawals were appealed; alternative antimicrobials were ordered following 20% of withdrawals; no incident infections, readmissions or in-hospital deaths were definitively attributed to withdrawal intervention. Our antimicrobial withdrawal intervention was a safe and effective addition to ASP activities to reduce inappropriate antimicrobial use and improve prescriber accountability.

Evaluating antibiotic therapy for ventilator-associated pneumonia caused by gram-negative bacilli

IntroductionVentilator-associated pneumonias (VAPs) are a complication of mechanical ventilation in the intensive care unit (ICU) that increase length of stay, morbidity, and mortality. While identifying and treating infections early is paramount to improving patient outcomes, more and more data demonstrate limited courses of antibiotics improve outcomes. Prolonged (10–14 day) courses of antibiotics have remained the standard of care for pneumonia due to gram-negative bacilli (GNR). We aimed to review our GNR VAPs to assess risk factors for recurrent GNR infections. MethodsWe reviewed trauma patients who developed VAP from 02/2019 through 05/2022. Demographics, injury characteristics, and outcomes were reviewed with a focus on pneumonia details including the cultured pathogen(s), antibiotic(s) used, treatment duration, and presence of recurrent infections. We then compared single episode VAPs to multiple episode VAPs among patients infected by GNRs. ResultsEleven of the fifty trauma patients admitted to the ICU suffered a VAP caused by a GNR. Of these eleven patients, six experienced a recurrent infection, four of which were caused by Pseudomonas aeruginosa and two of which were caused by Enterobacter aerogenes. Among the patients who received ten days of antibiotic treatment, half suffered a recurrence. Although, there was no difference in the microbiology or antibiotic duration between the recurrences and single episodes. ConclusionDespite prolonged use of antibiotics, we found that the risk of recurrent or persistent infections was high among patients with VAP due to GNB. Further study is needed to determine optimal treatment to minimize the risk of these recurrences. Key messageVentilator-associated pneumonia due to gram-negative bacilli is a rare but high morbidity complication in intensive care units. Despite prolonged duration of therapy, these infections still appear to account for many recurrent infections and further study into optimal therapy is warranted.

Long-term gastrointestinal adverse effects of doxycycline.

Doxycycline is an antibiotic with known gastrointestinal (GI) adverse effects. Esophagitis is the most pronounced among these effects, and might be associated with a prolonged duration of therapy. The aim of this study is to evaluate the incidence of esophagitis and other GI side effects in adults who received doxycycline for at least a month. This retrospective descriptive study included adults who received oral doxycycline for at least one month between 2016 and 2018. The primary outcome was the frequency of esophagitis. The secondary outcomes were frequency of and discontinuation due to GI adverse effects. A total of 189 subjects were included with a median age of 32 years. The median duration of doxycycline use was 44 days (interquartile range 30-60). Twelve patients (6.3%) reported having GI adverse effects resulting in doxycycline discontinuation in five of them (2.6%), and three patients (1.6%) had esophagitis. The incidence of GI adverse effects was significantly higher in patients who were ≥ 50 years than < 50 years old (8/50 vs. 4/139; p = 0.003) and in those who received a daily dose of 200 mg than 100 mg (12/93 vs. 0/96; p < 0.001). GI adverse events, including esophagitis, are not rare with long-term use of oral doxycycline, particularly in older age and a higher dose of 200 mg/day. Future large and randomized studies are needed to compare the efficacy and safety of different doxycycline doses.

INVESTIGATION OF RISK FACTORS AND BACTERIAL PATHOGENS OF SURGICAL SITE INFECTIONS IN A TEACHING HOSPITAL IN HYDERABAD

Background: Surgical site infections are one of the most common healthcare associated infections which results in a delay in patient recovery. These infections being the most common HAI in our area, the present study was conducted to know the incidence of SSIs and to detect the risk factors associated with SSIs. Material and methods: A prospective study on SSIs was conducted over a period of seven months involving 1211 patients. History was taken from these patients regarding the risk factors of SSIs. Pus and wound swabs collected from these patients were subjected to culture. The culture isolates were identified by standard biochemical tests. Antibiotic sensitivity testing was performed using standard protocol. The incidence of SSIs was determined. Results: SSI rate was 6.6 %.The most common risk factors associated with SSIs were age &gt;60 years, diabetes followed by obesity and prolonged duration of surgery. There was no association with smoking, malnutrition, immunosuppression, skin colonization at the time of surgery, presence of skin diseases at the incision site, peripheral vascular disease and anaemia. Majority of isolates were gram negative isolates. Klebsiella and Escherichia coli were the most common isolates. There was maximum sensitivity of isolates to carbapenems and combination drugs. Conclusion: Age&gt;60 years, diabetics, obesity, and prolonged duration of therapy were the major risk factors associated with SSIs. Decreased incidence of SSIs &amp; decreased isolation of exogenous pathogens in SSI, high sensitivity of gram negative bacilli in our study suggests good infection control practices in our hospital area.

Step-up titration dosing (TD) of carfilzomib (K) is associated with prolonged duration of therapy and improved treatment outcomes compared to standard dosing (SD) in patients with multiple myeloma (MM).

e20016 Background: K is a 2nd-generation proteasome inhibitor (PI) approved for the treatment of multiple myeloma (MM). K-based regimens are associated with higher rates of CV toxicity compared with other PIs. We conducted a retrospective analysis to assess incidence of CV adverse events (AE) and outcomes of MM patients (pts) treated with K using a step-up TD schedule compared to SD protocol. Methods: A retrospective chart review was performed of MM pts treated with K at The Ohio State University Comprehensive Cancer Center (OSUCCC) from 1/1/13 to 9/1/19. Pt demographics, disease and K-related characteristics, CV AE, and follow-up information were collected. Pts were excluded if treated at both local center and at OSUCCC, not K-naïve when receiving treatment at OSUCCC, received a single dose of K while inpatient with no intent to continue treatment outpatient, or had a treatment plan entered but never received it. Results: Of the 166 pt charts analyzed, 36 were treated using a TD method (ex. step-wise C1D1 20mg/m2, C1D8 27mg/m2, C1D15 36mg/m2, for goal C2D1 56mg/m2 onwards) and 130 pts were treated using a standard dosing method (ex. C1D1 20mg/m2 and C1D8 56mg/m2 onwards). Pre-existing CV risk factors were similar between the two groups. There was a slight difference in baseline renal function (TD: median CrCl 94mL/min, SD: 76mL/min; p=0.01) and prior PI use (TD: 86.1%, SD: 95%; p=0.048) between the two groups. In pts treated with TD, hypertension (HTN) developed earlier compared with SD (p=0.02). There was a lower incidence of onset of dyspnea in the TD group compared to SD group (16.7% vs 36.2%, respectively; p=0.03). There were no differences in incidence of HTN, congestive heart failure, ischemic heart disease, arrythmias, or pulmonary HTN. The median number of cycles administered to titrated pts was 7 (range: 2-56) compared to 3 (range: 1-44) for standard pts (p&lt;0.001). There was no statistical difference in CV AE being the cause for treatment discontinuation between the two groups. The overall response rate (ORR) was higher in the TD group compared to the SD group (63.9% vs 42.8%, respectively; p=0.04). Five-year overall survival (OS) was improved in patients treated with TD than with SD (43.8% vs 17.5%, respectively; p&lt;0.001). By multivariable analysis, TD was associated with improved OS compared to SD (HR 0.47; 95% CI 0.29-0.77-3.58; P=0.003). Conclusions: A simple modification of K titration dosing improved the tolerability of MM therapy without compromising efficacy. Although there were no differences in AE being the cause of treatment discontinuation between the two groups, an improvement in duration of therapy, ORR, and OS was observed in the TD group. As a result, TD is the standard-of-care dosing for MM pts treated with K at the OSUCCC. Prospective trials are needed to confirm the safety and efficacy of this dosing regimen.

146. Predictors of Long Duration Antibiotic Therapy for Urinary Tract Infections and Community-Acquired Pneumonia in Pediatric Ambulatory Care Settings

BackgroundSignificant variation exists in the duration of antibiotic therapy for children in ambulatory care settings. Understanding drivers of variation for common conditions such as community-acquired pneumonia (CAP) and urinary tract infection (UTI) is important to informing antimicrobial stewardship interventions. MethodsA retrospective observational study was conducted of patients with CAP and UTI seen in outpatient clinics or discharged from the emergency room (ER) of a tertiary care children’s hospital network from 2016 – 2019. Diagnoses CAP and UTI were identified via ICD-10 coding. Only oral medications ordered for ≥ 3 and < 28 days were included. Multivariable logistic regression was performed to identify predictors of long antibiotic duration (defined as ≥ 10 days). Potential non-clinical drivers of longer duration included race, ethnicity, sex, primary language, and insurance status. ResultsA total of 2,104 prescriptions for CAP from 442 prescribers and 1,070 prescriptions for UTI from 314 prescribers were included. Antibiotic durations were ≥ 10 days in 59.9% and 47.6% of prescriptions for CAP and UTI, respectively. Long duration of therapy was more common in children discharged from the ER when compared to clinics for both CAP (OR 1.795, 95% CI: 1.107 - 2.929), and UTI (OR 5.149, 95% CI: 1.933 - 16.373). The proportion of patients with long duration of therapy increased with younger age for both diagnoses and decreased overall in the final year of the study. Race, gender, ethnicity, and primary language were not associated with prolonged duration of therapy. However, patients with Medicaid insurance were more likely to receive long duration of therapy for CAP (OR 1.337, 95% CI: 1.062 - 1.682) and UTI (1.654, 95%, CI: 1.181 - 2.325). ConclusionIn pediatric patients in ambulatory care settings, younger age, care in the ER, and being insured through Medicaid were independently associated with prolonged duration of therapy for both UTI and CAP.Disclosures All Authors: No reported disclosures

Treating CLL with Bruton Tyrosine Kinase Inhibitors: The Role of the Outpatient Oncology Nurse.

To summarize the role of Bruton tyrosine kinase (BTK) inhibitors in the management of chronic lymphocytic leukemia with a focus on the nursing role in relation to patients with chronic lymphocytic leukemia being treated with BTK inhibitors. These include published articles (PubMed) and national and international guideline documents. BTK inhibitors have revolutionized the therapy of chronic lymphocytic leukemia and have become the most frequently used therapy today. Despite the many advantages of BTK inhibitors, adverse events remain a leading cause of treatment discontinuation, particularly for the first-in-class BTK inhibitor. Second-generation BTK inhibitors appear to have a better tolerability profile but still require adverse event management given their prolonged duration of therapy. Awareness and management of side effects by the oncology care team is essential for ensuring both compliance and safety with ongoing treatment. Chronic lymphocytic leukemia is a chronic illness with a long-life expectancy. For the patients who require therapy, BTK inhibitor therapy is a frequently applied treatment with impressive efficacy. BTK inhibitors are continued indefinitely until disease progression or significant toxicity; therefore, the overall principles of careful assessment for side effects, diligent management for these, and individualized patient support provided by oncology nurses is vital in this patient population.

Profile of the adverse drug reactions among the multidrug resistant tuberculosis patients treated at a tertiary level hospital in southern India

Background: The prevalence of multi-drug resistant tuberculosis (MDR-TB) is increasing worldwide. The treatment of MDR-TB is challenging due to its delayed diagnosis, prolonged duration of therapy with larger number of drugs, coupled with their great potential for adverse drug reactions (ADRs), which severely impair treatment adherence. Early identification and effective management of ADRs form the cornerstone to ensure treatment adherence, which is an essential aspect in better treatment outcome. Materials and Methods: A prospective observational study was conducted for a period of 3 years, at Basaveshwara Medical College and Hospital, Chitradurga. All MDR-TB patients who fulfilled study criteria were included in study. After pre-treatment clinical evaluation, necessary radiological, serological and bacteriological investigations, patients were treated by Cat IV regimen for MDR TB and monitored for development of ADRs and treated appropriately. Results: Mean age of patients was 38 ± 3.6 years. A 70.9% of patients had low body mass index (BMI). A 74.5% of patients got successfully cured. ADRs were reported among 52.6% of patients. GI intolerance (49.1% in intensive phase) and psychiatric symptoms (41.8% in continuation phase) were most common ADRs reported. Low BMI was found to be significantly associated with ADRs. Conclusion: Meticulous and regular follow-ups with emphasis on early detection of ADRs during the course of ATT, dosage adjustments to effectively manage ADRs, addressing problem of malnutrition, a compulsory psychiatrist opinion as part of pre-treatment evaluation and also during continuation phase of ATT to detect the emergence of psychiatric symptoms, will go a long way in achieving high rates of favourable outcomes among MDR-TB patients. Keywords: Adverse drug reactions; Depression; Suicidal tendencies; Malnutrition; Gastro-intestinal intolerance.

In-Class Transition (iCT) from Parenteral Bortezomib to Oral Ixazomib Proteasome Inhibitor (PI) Therapy Increases the Feasibility of Long-Term PI Treatment and Benefit for Newly Diagnosed Multiple Myeloma (NDMM) Patients in an Outpatient Setting: Updated Real-World Results from the Community-Based United States (US) MM-6 Study

In-Class Transition (iCT) from Parenteral Bortezomib to Oral Ixazomib Proteasome Inhibitor (PI) Therapy Increases the Feasibility of Long-Term PI Treatment and Benefit for Newly Diagnosed Multiple Myeloma (NDMM) Patients in an Outpatient Setting: Updated Real-World Results from the Community-Based United States (US) MM-6 Study

Implementing outpatient antimicrobial stewardship in a primary care office through ambulatory care pharmacist-led audit and feedback

ObjectivesThis study aimed to determine the impact of a pharmacist-led antimicrobial stewardship program (ASP) intervention on outpatient antibiotic prescribing for upper respiratory tract infections (URIs) and urinary tract infections (UTIs) in a primary care office. The primary outcome of this study was to characterize antibiotic prescribing over time. Secondary outcomes included describing ambulatory care pharmacist (ACP) workload and types of feedback given. MethodsA retrospective pilot study was conducted within a primary care office. The office included a 0.6 full-time equivalent ACP and is part of a health system supported by a pharmacist and a physician co-led ASP. Education and guidelines were provided by the ACP and ASP leads before the intervention period August 2017–February 2018. The ACP provided bi-weekly audit of all URI and UTI prescriptions and written feedback to prescribers. ResultsDuring the 7-month intervention period, 1107 prescriptions were audited by the ACP, 825 URI and 282 UTI. The most common reasons for feedback included inappropriate agent (26.3%) or prolonged duration of therapy (24.3%). Guideline-concordant agent prescribed for a UTI increased from 20% at baseline to a median of 69.2%, whereas duration increased from 55% to 70.4%. Guideline-concordant agent prescribed for a URI increased from 43.3% to 86.8%, whereas the median duration of therapy decreased from 10 to 7 days. ConclusionAn ACP-led ASP intervention within a primary care office incorporating audit and feedback improved antibiotic prescribing for URIs and UTIs, including prescribing antibiotics when indicated, guideline-concordant antibiotic selection, and duration of therapy. Pharmacists practicing in ambulatory care settings may serve a vital role in leading successful outpatient ASP interventions.

Bacterial pneumonia coinfection and antimicrobial therapy duration in SARS-CoV-2 (COVID-19) infection.

BackgroundBacterial respiratory coinfection in the setting of SARS-CoV-2 infection remains poorly described. A description of coinfection and antimicrobial usage is needed to guide ongoing antimicrobial stewardship.ObjectivesTo assess the rate of empirical antimicrobial treatment in COVID-19 cases, assess the rate and methods of microbiological sampling, assess the rate of bacterial respiratory coinfections and evaluate the factors associated with antimicrobial therapy in this cohort.MethodsInpatients with positive SARS-CoV-2 PCR were recruited. Antibiotic prescription, choice and duration were recorded. Taking of microbiological samples (sputum culture, blood culture, urinary antigens) and culture positivity rate was also recorded. Linear regression was performed to determine factors associated with prolonged antimicrobial administration.ResultsA total of 117 patients were recruited; 84 (72%) were prescribed antimicrobial therapy for lower respiratory tract infections. Respiratory pathogens were identified in seven (6%) patients. The median duration of antimicrobial therapy was 7 days. C-reactive protein level, oxygen requirement and positive cultures were associated with prolonged duration of therapy. ConclusionsThe rate of bacterial coinfection in SARS-CoV-2 is low. Despite this, prolonged courses of antimicrobial therapy were prescribed in our cohort. We recommend active antimicrobial stewardship in COVID-19 cases to ensure appropriate antimicrobial prescribing.

T-DM1 Efficacy in Patients With HER2-positive Metastatic Breast Cancer Progressing After a Taxane Plus Pertuzumab and Trastuzumab: An Italian Multicenter Observational Study

BackgroundT-DM1 improves progression-free survival (PFS) and overall survival (OS) in patients with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer progressing on prior trastuzumab plus a taxane. A paucity of data is available on T-DM1 efficacy after dual anti-HER2 blockade with pertuzumab and trastuzumab plus a taxane, which represents the current first-line standard of care. The present study is a retrospective/prospective evaluation of the efficacy and activity of second-line T-DM1 after front-line pertuzumab-based therapy. Patients and MethodsEligible patients were identified within the Gruppo Italiano Mammella (GIM) 14/BIOMETA study, a retrospective/prospective multicenter study on treatment patterns and outcomes of patients with metastatic breast cancer (ClinicalTrials.gov Identifier: NCT02284581). We searched for patients who received second-line T-DM1 after taxane plus trastuzumab and pertuzumab between November 15, 2013 and May 31, 2018. We calculated median PFS, median time to treatment failure (TTF), prolonged duration of therapy (PDT), objective response rate (ORR), and 1-year OS. ResultsOf 445 patients with HER2+ metastatic breast cancer, 77 were eligible for the analysis. At a median follow-up of 7 months, median PFS was 6.3 months (95% confidence intervals [CI], 4.8-7.7 months), and median TTF was 6.2 months (95% CI, 4-8.6 months). More than one-third of patients (37.6%; n = 29) experienced PDT with an ORR of 27.1%. At data cutoff, the median OS was not reached, and the 1-year OS was 82%. ConclusionsOur results show meaningful activity of T-DM1 after front-line pertuzumab plus trastuzumab and a taxane, with about 27% of patients having an objective response and 40% of patients achieving durable disease control.

Influencing duration of antibiotic therapy: A behavior change analysis in long-term care

Prolonged antibiotic duration of therapy is common in long-term care (LTC) settings and associated with increased risk of harm for residents. To identify potential antibiotic stewardship opportunities aimed at prolonged duration of therapy, this study examined barriers and enablers to using shorter courses of antibiotic therapy in the LTC setting. Semistructured interviews were conducted with prescribers in LTC home settings, and a total of 8 LTC clinicians participated in the study. Questions and clinical scenarios explored the factors influencing the decisions of prescribers about duration of therapy. Using the Theoretical Domains Framework, interview data were analyzed deductively. The themes identified that influence duration of antibiotic therapy in LTC were environmental context and resources, knowledge, beliefs about consequences, social influences, and behavioral regulation. Specific concerns described by participants included the perceived lack of evidence to support shorter courses in LTC residents, the misconception that shorter courses could lead to greater rates of resistance, and the strong role of habit and prior experience in selecting antibiotic duration. There are several factors affecting antimicrobial duration prescribing behavior aside from the clinical scenario itself. Tackling misconceptions and providing educational support may be helpful approaches. These findings provide theory-informed evidence to support the development of antimicrobial stewardship interventions aimed at improving duration of antibiotic therapy.

Abstract P6-18-26: Ado-trastuzumab for the treatment of metastatic HER2-amplified breast cancer patients previously treated with pertuzumab

Abstract BACKGROUND: Ado-trastuzumab (T-DM1) is an antibody-drug conjugate of trastuzumab and a cytotoxic microtubule-inhibitory agent, emtansine. T-DM1 is approved for the treatment of advanced HER2-amplified breast cancer that progressed following trastuzumab-based therapies based on improvement in progression-free survival (PFS) and overall survival (OS) compared to the therapy of physician choice. However, T-DM1 trials were conducted prior to the widespread adoption of docetaxel, trastuzumab, and pertuzumab as standard frontline therapy for advanced HER2-amplified breast cancer. As such, none of the patients enrolled on T-DM1 studies had been exposed to pertuzumab, and the clinical benefit of T-DM1 in patients previously treated with pertuzumab therapy is unknown. METHODS: We completed a retrospective review of patients at our institution over the age of 18 with metastatic HER2-amplified breast cancer treated with pertuzumab prior to T-DM1 between February 2013 and May 2018. Data was collected on patient and tumor characteristics, number and duration of therapies in the metastatic setting, and clinical outcomes. The primary endpoint of this study was PFS in patients given T-DM1 after earlier exposure to pertuzumab. Secondary endpoints included overall response rate (ORR), prolonged duration of T-DM1 therapy (&amp;gt; 6 months), and OS. Adverse events following T-DM1 were collected using CTCAE 4.03, with a focus on cardiac dysfunction and peripheral neuropathy. Patient features and outcomes were summarized with descriptive statistics and time-to-event measures were analyzed using the Kaplan-Meier method and log-rank test. RESULTS: Twenty patients met the inclusion criteria and are included in this study. The patient population consisted of 18 non-Hispanic white and 2 black women, with a median age of 58.5 (range 34-68) years. The number of prior systemic therapies (excluding pertuzumab) ranged from 0-8 with a median of 1 therapy. The duration of T-DM1 therapy (started, on average, 24 months after metastatic diagnosis) ranged from &amp;lt; 1 month to 3.5 years with a median of 6 months. T-DM1 therapy was overall very well tolerated, with all adverse events being grade ≤2. Of note, 2 patients had grade 2 neuropathy, and one patient had grade 1 cardiotoxicity, without any change in left ventricular ejection. Among 18 patients evaluable for response, ORR was 16.7% (95% CI: 3.6% to 41.4%), with 3 patients achieving a partial response. No complete responses were noted. 10/18 (55.6%) patients had prolonged duration of therapy with T-DM1. Median follow-up time after initiation of T-DM1 was 15 months and 6/20 (30%) patients died while under observation. At the time of data cut-off, 10/20 patients had disease progression on T-DM1. Median PFS was 16 months, with a 1-year PFS rate of 54.5% (95% CI: 36.4% to 81.7%). The 1-year OS rate was 75.0% (95% CI: 58.2% to 96.6%). Patients with liver metastases (n=8) had a significantly worse PFS (p=0.003). CONCLUSION: T-DM1 following pertuzumab is well tolerated and shows excellent efficacy in the treatment of HER2-positive metastatic breast cancer. Comparing T-DM1 following pertuzumab to T-DM1 in pertuzumab-naïve patients should be explored in this patient population. Citation Format: Al Rabadi LS, Kaempf A, Lim JY, Saraceni MM, Savin MA, Mitri ZI. Ado-trastuzumab for the treatment of metastatic HER2-amplified breast cancer patients previously treated with pertuzumab [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-26.

Management and outcome of Stevens–Johnson syndrome and toxic epidermal necrolysis in patients admitted to Kenyatta National Hospital

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous drug reactions requiring intensive care and protracted hospitalization. Local data on their characteristics, management and outcomes are minimal. Our objective was to identify the complications of SJS/TEN and the management strategies employed and the effect of these on patient mortality. We conducted a retrospective cross-sectional study to determine the characteristics, management strategies and patient mortality associated with SJS/TEN in patients admitted to Kenyatta National Hospital from June 2006 to June 2016. Total population sampling was used to identify 115 patients with SJS/TEN. Data on disease complications, management strategies employed and mortality status as an outcome of therapy were extracted. Patients were predominantly managed using antimicrobials (16.4% of patients, 21.8% of whom received topical mupirocin). Fluid and electrolyte replacement, skin emolliation with liquid paraffin, temperature regulation and corticosteroids were used to treat 15.3, 13.4, 11.1 and 9.4% of patients, respectively. The mortality rate was 21.7%. Significantly (p ≤ 0.05) higher mortality was associated with patients’ area of residence, disease subclass, disease severity score, hypokalaemia, dyspnoea, haematological disturbance, sepsis and dehydration. Conversely, use of total parenteral nutrition, anticoagulants for deep venous thrombosis prophylaxis and prolonged duration of therapy were associated with significantly (p ≤ 0.001) lower mortality. Mortality was not associated with administration of corticosteroids or antibiotics. Independent predictors of mortality were hypokalaemia, dyspnoea, haematological disturbance and sepsis (all p ≤ 0.05). The main management strategy used to treat SJS/TEN was antimicrobial prophylaxis, but this was not correlated with mortality. Mortality was high and was attributed to distant patient residence, severe disease and complications, suggesting that early recognition of these signs could avert mortality.

Prolonged Duration of Therapy Is Associated With Improved Survival in Patients Treated for Relapsed/Refractory Multiple Myeloma in Routine Clinical Care in the United States

BackgroundIn clinical trials, an extended therapy duration has been associated with better outcomes in patients with newly diagnosed multiple myeloma (NDMM). However, data on how the therapy duration affects the outcomes for patients with relapsed/refractory multiple myeloma (RRMM) are limited. We conducted a large, retrospective study in the United States to evaluate the effect of the duration of second-line therapy on overall survival. Patients and MethodsAdults with NDMM from January 2008 to June 2015 were followed up to identify their second-line therapy. The duration of therapy (DOT) and time to next therapy (TTNT), as a proxy for progression-free survival, were estimated using the Kaplan-Meier method. The relationship between the duration of second-line therapy and overall survival was evaluated with a logistic marginal structural model to mitigate the risk of treatment selection and survival bias. ResultsA total of 628 NDMM patients developed a relapse after initial therapy. The median DOT for second-line therapy was 6.9 months (95% confidence interval [CI], 5.9-7.7 months), which was shorter than the corresponding TTNT (median, 15.1 months; 95% CI, 13.4-17.3 months). Each additional month of second-line therapy was associated with a reduced adjusted risk of death at 1 year (odds ratio, 0.78; 95% CI, 0.77-0.83; P < .001). ConclusionIn a large database capturing a heterogeneous patient population and varied treatment patterns reflecting routine clinical care, we found a clinical benefit for continued longer DOT at first relapse. Despite the emerging paradigm favoring continuous therapy, second-line progression-free survival (utilizing TTNT as the proxy) was more than twofold longer than the DOT. Understanding the barriers to extended DOT could help to improve the outcomes for RRMM patients.

COMPARATIVE ORCHIDOTOXICITY STUDY BETWEEN CHLOROQUINE PHOSPHATE AND HYDROXYCHLOROQUINE SULFATE ON ADULT ALBINO RATS

Introduction: Chloroquine phosphate (CQP) and hydroxychloroquine sulfate (HCS) are antimalarial drugs commonly used for treatment of malaria and numerous rheumatic diseases. Their widespread prescriptions may accompany with prolonged duration of therapy and higher daily dosages, leading to several toxic effects, including disturbance of reproductive system. Aim of the study: The present study was designed to compare the effect of six-week exposure to CQP and HCS on reproductive function of adult male albino rats. Materials and Methods: The study was conducted on 30 normal adult male albino rats divided equally into 3 groups (10 rats each), the Control-group (C-group) was given 1 ml of distilled water orally, whereas the CQPgroup (62 mg/kg/b. wt. ) and HCS-group (124 mg/kg/b. wt. ) were given single daily oral doses equivalent to 1/10th of LD50 of each drug for 6 consecutive weeks then all animals sacrificed. The serum levels of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH), quality of epididymal sperm (count, motility, viability, and morphology), degeneration severity of seminiferous tubules (SNT) and Leydig cells count per each animal, semi-quantitative scoring of SNT and Leydig cells histopathological changes, spermatogenesis maturity levels, and structural and ultrastructural morphologies of tissues were estimated. Results: The CQP-group showed severe orchidotoxic effects as manifested by statistically significant reductions in final weight gains of body, testes, and epididymis, all sperm quality, and all hormone levels, marked increases in the number of animals associated with SNT degeneration and reduced Leydig cells count, statistically significant increases in abnormalities of SNT and Leydig cells architectures, statistically significant decrease of spermatogenesis maturity levels, and extensive structural and ultrastructural changes in testicular parenchyma and interstitial tissues as compared to C-group and HCS-group. While, HCS-group displayed minor orchidotoxic effects as evidenced by insignificant changes in most of the evaluated parameters, significant reductions of LH and FSH levels, slight increases in the number of animals accompanied with SNT degeneration and reduced Leydig cells count, and minor changes of structural and ultrastructural testicular tissue architectures as compared to C-group. Conclusion, these results suggest that CQP has more orchidotoxic effects than HCS, and in terms of therapeutic usage, physicians should better prescribe HCS as it appears safer than CQP. Also, assessment of male reproductive functions should be done periodically for patients receiving both drugs for prolonged time, especially CQP, as they may induce endocrine disruptions.

Lack of Benefit With Combination Therapy for Clostridium difficile Infection.

Limited data exist regarding combination therapy for Clostridium difficile infection (CDI). After adjusting for confounders in a cohort of patients with CDI and≥1 year old, combination therapy was not associated with significant differences in clinical outcomes, but it was associated with prolonged duration of therapy (1.22 days; 95% confidence interval, 1.03-1.44 days; P=.02). Infect Control Hosp Epidemiol 2017;38:602-605.

High-Dose rifampicin: Time to dose it right!

Tuberculosis (TB) remains a major cause of mortality worldwide. Effective control of TB is being hampered by the prolonged duration of therapy which leads to poor patient compliance. This can lead to increased relapse rates and emergence of drug-resistant organisms, thus further compounding the problem. An exciting new avenue to reduce the duration of therapy is the use of high-dose rifampicin. High-dose rifampicin is being extensively studied and the data is exciting. It has shown to result in better sterilization and earlier culture conversion with no increase in adverse reactions. These effects of high-dose rifampicin can possibly help reduce the duration of TB treatment. Whether this “high-dose-reduced-duration-rifampicin-regimen” will lead to increased relapse rates is yet to be studied. If not, then this gives physicians a well proven and inexpensive option to cure TB and hence may be the future of TB treatment.