Tigecycline 50mg powder for solution for infusion vials

Guideline-based combination therapy achieves sputum culture conversion rates in 23%-34% of patients with Mycobacterium abscessus-complex lung disease. Thus, new therapies are needed. We performed a systematic review to validate and benchmark the hollow fiber system model of M. abscessus lung disease for drug development. We performed a literature search to identify all published hollow fiber system pharmacokinetic-pharmacodynamic studies. Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used for bias minimization. A total of 12 studies were identified. The average quality score was 13.7 out of 21. Eight were monotherapy (exposure-effect and dose-fractionation), one double β-lactam, and three guideline-based therapy studies. For omadacycline and imipenem, hollow fiber system data were accompanied by clinical real-world evidence confirmation. Microbial kill was always terminated by antimicrobial resistance. We used quantitative analyses to rank drugs' efficacy based on CFU/mL kill below day 0 bacterial burden normalized to multi-drug guideline-based therapy kill. The highest-ranked drugs were sulbactam-durlobactam-ceftriaxone (177-fold), epetraborole (15-fold), and omadacycline (7-fold) better than guideline-based therapy. We used the target exposures identified in the systematic analysis in Monte Carlo experiments to identify optimal doses for inhaled formulations. The optimal inhalational dose of imipenem was 250 mg/day, for tigecycline 4 mg/day, for cefoxitin 50 mg/day, and for amikacin liposome inhalation suspension 590 mg once weekly. The hollow fiber system model of M. abscessus lung disease is tractable for exposure-effect, dose-fractionation, and factorial design combination studies. It could also be used to rank drugs and inform on which drugs to test in novel combinations.IMPORTANCECurrent treatments for Mycobacterium abscessus lung disease fail in 70%-80% of patients and are toxic. The hollow fiber system has been used to study old and new potential treatments for this disease. We performed a systematic review of this methodology, for lessons learned. We found 12 studies, which were of adequate quality. Efficacy was always terminated by antimicrobial resistance. The top three drugs in terms of efficacy were sulbactam-durlobactam-ceftriaxone, epetraborole, and omadacycline, which were 7 to 177 times better than standard of care. These drugs could be combined into a new treatment regimen better than current treatments. We also calculated new doses for imipenem, tigecycline, cefoxitin, and amikacin when administered as inhalational therapy. The inhaled doses were multiple-fold lower than intravenous ones, which could be less toxic. The hollow fiber system model is an easily managed system from drug development and dose finding for M. abscessus lung disease.

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ObjectivesTo evaluate the clinical efficacy and survival benefits of alternative antimicrobial regimens compared to conventional TMP-SMX in treating multidrug-resistant Stenotrophomonas maltophilia infections.MethodsWe searched PubMed, Embase, Cochrane, and Web of Science up to April 2026 for cohorts comparing TMP-SMX, levofloxacin, minocycline, and tigecycline. A frequentist random-effects network meta-analysis was performed. Primary outcomes were overall survival and clinical efficacy (odds ratios [ORs] with 95% CIs). Treatments were ranked by SUCRA.ResultsFifteen cohorts were included. Levofloxacin significantly improved survival versus TMP-SMX (OR = 2.01, 95%CI 1.16-3.47, P = 0.012). Tigecycline showed the highest clinical response (OR = 4.97, 95%CI 1.69-14.61, P = 0.004) but no survival benefit. SUCRA ranked levofloxacin first for mortality reduction (91.3%) and tigecycline first for efficacy (91.3%); minocycline performed consistently across endpoints.ConclusionsA "survival paradox" exists in SMA treatment: tigecycline yields superior initial response without improving survival, whereas levofloxacin provides the most significant survival benefit. Levofloxacin should be prioritized for critically ill patients, while high-dose TMP-SMX and tigecycline warrant cautious re-evaluation.

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BackgroundVentilator-associated pneumonia (VAP) is a common and serious nosocomial infection in mechanically ventilated preterm infants and is increasingly caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative organisms. Tigecycline, a glycylcycline with broad activity against many such pathogens, is not approved below 18 years of age and carries a boxed warning for excess mortality that is most pronounced in hospital-acquired and ventilator-associated pneumonia. Its role, if any, in preterm infants with VAP is undefined.ObjectivesTo systematically identify and appraise all human evidence on the efficacy (clinical cure, microbiological eradication, survival) and safety (adverse events, mortality) of tigecycline used to treat VAP or nosocomial pneumonia during mechanical ventilation in preterm infants and neonates.MethodsA PRISMA 2020 structured search of PubMed/MEDLINE, Cochrane CENTRAL, Scopus, trial registries, regulatory documents, Google Scholar and reference lists was designed without language or date restrictions. Eligible reports described tigecycline treatment of pneumonia/VAP in neonates or young infants; pediatric case series and syntheses were retained as contextual evidence. Because only case reports and small non-comparative series were anticipated, a narrative synthesis was pre-specified; JBI tools and GRADE were planned for appraisal and certainty.ResultsNo randomized controlled trial, controlled observational study, or study dedicated to tigecycline for VAP in preterm infants was identified. Direct evidence meeting the full eligibility criteria (preterm neonate, VAP specifically, separately extractable outcomes) was limited to two case reports of extremely preterm neonates with VAP successfully weaned after tigecycline-based salvage combination therapy. Six further neonatal/young-infant reports initially considered were, on full-text re-review, reclassified as contextual (not index) evidence because they described non-VAP infections (sepsis, or CNS infections such as ventriculitis/meningitis), non-preterm ages, or mixed-infection series without separable VAP data. Reported outcomes were generally favorable in published cases but are subject to severe selection and publication bias; thrombocytopenia, hypofibrinogenemia and hepatic enzyme elevation were the principal adverse signals, against a class-level mortality signal concentrated in VAP. Quantitative pooling was not appropriate. The overall certainty of evidence was very low.ConclusionsThere is no direct, credible efficacy or safety evidence supporting tigecycline for VAP in preterm infants. Available data neither establish benefit nor exclude harm. Based on this very-low-certainty evidence and on regulatory/class-level safety data rather than on demonstrated efficacy, tigecycline warrants consideration only as a last-resort, combination salvage option for culture-confirmed pan- or extensively drug-resistant pathogens when no safer alternative exists, with intensive monitoring and, ideally, within a registry or trial. Adequately designed neonatal pharmacokinetic and comparative safety studies are urgently needed.RegistrationPROSPERO CRD420261450972 (registered 14 July 2026).

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