Safety and effectiveness of low-dose amikacin in nontuberculous mycobacterial pulmonary disease treated in Toronto, Canada

Amikacin; NTM lung disease; Nontuberculous mycobacteriaAmikacina; Malaltia pulmonar per micobacteri no tuberculós; Micobacteri no tuberculósAmikacina; Enfermedad pulmonar por micobacteria no tuberculosa; Micobacteria no tuberculosaBACKGROUND: Treatment guidelines suggest either a low-dose or high-dose approach when prescribing amikacin for nontuberculous mycobacterial pulmonary disease (NTM PD), but data supporting the low-dose approach are limited. The purpose of this study was to describe the safety and efficacy of the use of a low-dose of intravenous amikacin in a cohort of patients with NTM PD. METHODS: We retrospectively reviewed all patients with NTM PD who received amikacin at our institution between July 1, 2003 and February 28, 2017. Demographics, clinical, microbiological and radiological data, indication and dose of amikacin, and adverse drug effects were recorded. RESULTS: A total of 107 patients received a regimen containing amikacin for a median (IQR) of 7 (4-11) months. Seventy (65.4%) were female and the mean age (SD) was 58.3 (14.9) years. Amikacin was started at a median dose of 9.9 (2.5) mg/kg/day. Ototoxicity was observed in 30/77 (39%) patients and it was related to female sex (OR 4.96, 95%CI 1.24-19.87), and total dose of amikacin per bodyweight (OR 1.62, 95%CI 1.08-2.43). Patients of East Asian ethnicity were less likely to develop ototoxicity (0.24, 95%CI 0.06-0.95). Out of 96 patients who received amikacin for more than 3 months, 65 (67.7%) experienced symptom improvement and 30/62 (49.2%) converted their sputum to culture negative within a year. CONCLUSIONS: Patients with NTM PD treated with low-dose intravenous amikacin frequently developed ototoxicity, which was associated with female sex, and total dose of amikacin per bodyweight. Physicians should carefully consider dose, treatment duration, and long term prognosis in balancing risks and benefits of intravenous amikacin in NTM PD

Safety and effectiveness of low-dose amikacin in nontuberculous mycobacterial pulmonary disease treated in Toronto

Treatment guidelines suggest either a low-dose or high-dose approach when prescribing amikacin for nontuberculous mycobacterial pulmonary disease (NTM PD), but data supporting the low-dose approach are limited. The purpose of this study was to describe the safety and efficacy of the use of a low-dose of intravenous amikacin in a cohort of patients with NTM PD. We retrospectively reviewed all patients with NTM PD who received amikacin at our institution between July 1, 2003 and February 28, 2017. Demographics, clinical, microbiological and radiological data, indication and dose of amikacin, and adverse drug effects were recorded. A total of 107 patients received a regimen containing amikacin for a median (IQR) of 7 (4-11) months. Seventy (65.4%) were female and the mean age (SD) was 58.3 (14.9) years. Amikacin was started at a median dose of 9.9 (2.5) mg/kg/day. Ototoxicity was observed in 30/77 (39%) patients and it was related to female sex (OR 4.96, 95%CI 1.24-19.87), and total dose of amikacin per bodyweight (OR 1.62, 95%CI 1.08-2.43). Patients of East Asian ethnicity were less likely to develop ototoxicity (0.24, 95%CI 0.06-0.95). Out of 96 patients who received amikacin for more than 3 months, 65 (67.7%) experienced symptom improvement and 30/62 (49.2%) converted their sputum to culture negative within a year. Patients with NTM PD treated with low-dose intravenous amikacin frequently developed ototoxicity, which was associated with female sex, and total dose of amikacin per bodyweight. Physicians should carefully consider dose, treatment duration, and long term prognosis in balancing risks and benefits of intravenous amikacin in NTM PD

Treatment outcome definitions in nontuberculous mycobacterial pulmonary disease: an NTM-NET consensus statement

Nontuberculous mycobacterial pulmonary diseases (NTM-PD) are increasingly recognised as opportunistic infections of humans. These chronic pulmonary infections have two main presentations. The first is a fibro-cavitary disease, that occurs in patients with pre-existing pulmonary diseases, such as chronic obstructive pulmonary disease, bronchiectasis, previous tuberculosis or other structural lung disease. The second presentation is a nodular- bronchiectatic disease of primarily the lingula and middle lobe that tends to affect a middle- aged and elderly female population [1]. Treatment of NTM-PD requires long-term administration of complex multidrug therapies that are species-specific. Currently recommended regimens are supported by a very limited evidence base [2, 3]. The increasing incidence of NTM-PD has sparked increased interest in performing prospective randomised clinical trials [4]. One of the drawbacks of the existing case series and clinical trials is that they have applied different outcome measures [5]. This hampers meta-analyses, which are important in these still understudied infectious diseases. To enhance the quality and interpretability of the results of future trials and retrospective cohort studies, we aimed to formulate clear and broadly acceptable outcome definitions for NTM-PD treatment

Clinical Considerations for Routine Auditory and Vestibular Monitoring in Patients with Cystic Fibrosis

Purpose Specific classes of antibiotics, such as aminoglycosides, have well-established adverse events producing permanent hearing loss, tinnitus, and balance and/or vestibular problems (i.e., ototoxicity). Although these antibiotics are frequently used to treat pseudomonas and other bacterial infections in patients with cystic fibrosis (CF), there are no formalized recommendations describing approaches to implementation of guideline adherent ototoxicity monitoring as part of CF clinical care. Method This consensus statement was developed by the International Ototoxicity Management Working Group (IOMG) Ad Hoc Committee on Aminoglycoside Antibiotics to address the clinical need for ototoxicity management in CF patients treated with known ototoxic medications. These clinical protocol considerations were created using consensus opinion from a community of international experts and available evidence specific to patients with CF, as well as published national and international guidelines on ototoxicity monitoring. Results The IOMG advocates four clinical recommendations for implementing routine and guideline adherent ototoxicity management in patients with CF. These are (a) including questions about hearing, tinnitus, and balance/vestibular problems as part of the routine CF case history for all patients; (b) utilizing timely point-of-care measures; (c) establishing a baseline and conducting posttreatment evaluations for each course of intravenous ototoxic drug treatment; and (d) repeating annual hearing and vestibular evaluations for all patients with a history of ototoxic antibiotic exposure. Conclusion Increased efforts for implementation of an ototoxicity management program in the CF care team model will improve identification of ototoxicity signs and symptoms, allow for timely therapeutic follow-up, and provide the clinician and patient an opportunity to make an informed decision about potential treatment modifications to minimize adverse events

Inpatient Care of Community-Acquired Pneumonia: The Effect of Antimicrobial Guidelines on Clinical Outcomes and Drug Costs in Canadian Teaching Hospitals

BACKGROUND: Evidence supporting antibiotic treatment guidelines and respiratory quinolones (RQs) in community-acquired pneumonia (CAP) is limited

Eosinophilic Pneumonia in a Traveller Returning from Mexico

Peer Reviewe

Inpatient Care of Community-Acquired Pneumonia: The Effect of Antimicrobial Guidelines on Clinical Outcomes and Drug Costs in Canadian Teaching Hospitals

BACKGROUND: Evidence supporting antibiotic treatment guidelines and respiratory quinolones (RQs) in community-acquired pneumonia (CAP) is limited.OBJECTIVE: To study associations among guideline adherence, specific antibiotics, clinical outcomes and antibiotic costs.METHODS: A retrospective cohort study in three tertiary care universityteaching hospitals in Toronto, Ontario, studying CAP inpatientsbetween November 1997 and June 2000. The periodencompassed 12 months when an early version of empirical antibioticguidelines was used (early cohort) and 18 months when recent guidelines(including RQs) were used (recent cohort).RESULTS: Six hundred ninety-eight cases of CAP were reviewed,and 91% were guideline adherent. In multivariable analyses, no associationwas observed between guideline adherence and mortality orduration of hospitalization. Guideline-adherent cases received fewerantibiotics in both cohorts and 0.9 days less of intravenous antibiotics(P=0.04) in the recent cohort. There was no significant difference inantibiotic cost according to guideline adherence, but recent cohortguideline-adherent cases had lower drug costs than early cohortguideline-adherent cases. Antibiotic selection was associated with illnessseverity and was mirrored by clinical outcomes, despite controllingfor the pneumonia severity index (PSI). Treatment withanaerobic agents (odds ratio 2.7, P=0.001) or cephalosporin plusmacrolide (odds ratio 2.7, P=0.02) was associated with higher mortality.Treatment with RQ monotherapy was associated with a 2.3 dayshorter duration of intravenous therapy (Pud_less_than0.0001) and a $19.19lower total antibiotic cost (Pud_less_than0.0001).CONCLUSION: Findings support empirical treatment guidelinesfor CAP and their recommendations regarding RQs. The associationbetween mortality and anaerobic coverage or combination therapymay reflect prognostic information available at presentation but notcaptured by the PSI.Peer Reviewe

Comparison of Per Cent Predicted and Percentile Values for Pulmonary Function Test Interpretation

BACKGROUND: Pulmonary function tests (PFTs) are commonly interpreted as a fraction of predicted normal values, with an abnormal test often defined as less than 80% or greater than 120% of the predicted value. However, recommendations of the American Thoracic Society/European Respiratory Society suggest using a percentile-based approach to define an abnormal test (less than the fifth or greater than the 95th percentiles)