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Clinical Features, Antibiotic Susceptibility Profile, and Outcomes of Infectious Keratitis Caused by Stenotrophomonas maltophilia.

ABSTRACT: PURPOSE:Stenotrophomonas maltophilia, an uncommon cause of infectious keratitis, is difficult to treat because of its resistance to multiple antibiotics. The purpose of this study is to describe the clinical features, antibiotic susceptibility profile, and outcomes of S. maltophilia keratitis. METHODS:A retrospective review of records from 1987 to 2016 identified 26 eyes of 26 patients who were treated at the Bascom Palmer Eye Institute for an S. maltophilia corneal ulcer. Clinical data were analyzed as to predisposing factors, clinical presentation, antibiotic susceptibility, treatment selection, and clinical outcomes. RESULTS:Median age at presentation was 65 years (range, 16-98). Twelve patients were using topical corticosteroids, 8 patients had a history of penetrating keratoplasty, and 9 were contact lens wearers. All patients received topical antibiotics, 2 required therapeutic penetrating keratoplasty, and 1 was enucleated. At presentation, 57.7% (15/26) of the patients had visual acuity of 20/400 or worse. At the final visit, only 30.4% (7/23) of the patients had visual acuity worse than 20/400, whereas 65.2% (15/23) of the patients had 20/100 or better. Almost all isolates (25/26, 96.2%) were susceptible to fluoroquinolones and 77.3% (17/22) of them to polymyxin B/trimethoprim. Only 33.3% (5/15) of the tested isolates were susceptible to aminoglycosides and 58.3% (7/12) to cephalosporins. CONCLUSIONS:Infectious keratitis due to S. maltophilia presents a treatment challenge because of its resistance to aminoglycosides and cephalosporins, which are typically used for empiric broad-spectrum gram-negative coverage as fortified solutions. Fluoroquinolones and polymyxin B/trimethoprim should be considered instead in cases of S. maltophilia infection.

SUBMITTER: Palioura S

PROVIDER: S-EPMC5806132 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Clinical Features, Antibiotic Susceptibility Profile, and Outcomes of Infectious Keratitis Caused by Stenotrophomonas maltophilia.

Palioura Sotiria S Gibbons Allister A Miller Darlene D OʼBrien Terrence P TP Alfonso Eduardo C EC Spierer Oriel O

Cornea 20180301 3

<h4>Purpose</h4>Stenotrophomonas maltophilia, an uncommon cause of infectious keratitis, is difficult to treat because of its resistance to multiple antibiotics. The purpose of this study is to describe the clinical features, antibiotic susceptibility profile, and outcomes of S. maltophilia keratitis.<h4>Methods</h4>A retrospective review of records from 1987 to 2016 identified 26 eyes of 26 patients who were treated at the Bascom Palmer Eye Institute for an S. maltophilia corneal ulcer. Clinica ...[more]

PMID: 29408828

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Project description:BackgroundStenotrophomonas maltophilia is one of the most common emerging multi-drug resistant organisms found in the lungs of people with cystic fibrosis and its prevalence is increasing. Chronic infection with Stenotrophomonas maltophilia has recently been shown to be an independent predictor of pulmonary exacerbation requiring hospitalization and antibiotics. However, the role of antibiotic treatment of Stenotrophomonas maltophilia infection in people with cystic fibrosis is still unclear. This is an update of a previously published review.ObjectivesThe objective of our review is to assess the effectiveness of antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis. The primary objective is to assess this in relation to lung function and pulmonary exacerbations in the setting of acute pulmonary exacerbations. The secondary objective is to assess this in relation to the eradication of Stenotrophomonas maltophilia.Search methodsWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched a registry of ongoing trials and the reference lists of relevant articles and reviews. Date of latest search: 03 March 2020.Selection criteriaRandomized controlled trials of Stenotrophomonas maltophilia mono-infection or Stenotrophomonas maltophilia co-infection with Pseudomonas aeruginosa in either the setting of an acute pulmonary exacerbation or a chronic infection treated with suppressive antibiotic therapy.Data collection and analysisBoth authors independently assessed the trials identified by the search for potential inclusion in the review.Main resultsWe identified only one trial of antibiotic treatment of pulmonary exacerbations that included people with cystic fibrosis with Stenotrophomonas maltophilia. However, this trial had to be excluded because data was not available per pathogen.Authors' conclusionsThis review did not identify any evidence regarding the effectiveness of antibiotic treatment for Stenotrophomonas maltophilia in people with cystic fibrosis. Until such evidence becomes available, clinicians need to use their clinical judgement as to whether or not to treat Stenotrophomonas maltophilia infection in people with cystic fibrosis. Randomized clinical trials are needed to address these unanswered clinical questions.

Project description:Clinical strains of Stenotrophomonas maltophilia are often highly resistant to multiple antibiotics, although the mechanisms of resistance are generally poorly understood. Multidrug resistant (MDR) strains were readily selected by plating a sensitive reference strain of the organism individually onto a variety of antibiotics, including tetracycline, chloramphenicol, ciprofloxacin, and norfloxacin. Tetracycline-selected MDR strains typically showed cross-resistance to erythromycin and fluoroquinolones and, in some instances, aminoglycosides. MDR mutants selected with the other agents generally displayed resistance to chloramphenicol and fluoroquinolones only, although two MDR strains (e.g., K1385) were also resistant to erythromycin and hypersusceptible to aminoglycosides. Many of the MDR strains expressed either moderate or high levels of a novel outer membrane protein (OMP) of ca. 50 kDa molecular mass, a phenotype typical of MDR strains of Pseudomonas aeruginosa hyperexpressing drug efflux systems. Indeed, the 50-kDa OMP of these S. maltophilia MDR strains reacted with antibody to OprM, the outer membrane component of the MexAB-OprM MDR efflux system of P. aeruginosa. Similarly, a ca. 110-kDa cytoplasmic membrane protein of these MDR strains also reacted with antibody to the MexB component of the P. aeruginosa pump. The outer and cytoplasmic membranes of several clinical S. maltophilia strains also reacted with the anti-OprM and anti-MexB antibodies. N-terminal amino acid sequencing of a cyanogen bromide-generated peptide of the 50-kDa OMP of MDR strain K1385, dubbed SmeM (Stenotrophomonas multidrug efflux), revealed it to be very similar to a number of outer membrane multidrug efflux components of P. aeruginosa and Pseudomonas putida. Deletion of the L1 and L2 beta-lactamase genes confirmed that these enzymes were responsible for the bulk of the beta-lactam resistance of K1385 and its parent. Still, overexpression of the MDR efflux mechanism in an L1- and L2-deficient derivative of K1385 did yield a modest increase in resistance to a few beta-lactams. These data are consistent with the MDR efflux mechanism(s) playing a role in the multidrug resistance of S. maltophilia.

Project description:BACKGROUND:Stenotrophomonas maltophilia, an opportunistic pathogen, is ubiquitously present in various environments, signifying its high capability of environmental adaptation. Two-component regulatory system (TCS) is a powerful implement to help organisms to survive in different environments. In clinic, treatment of S. maltophilia infection is difficult because it is naturally resistant to many antibiotics, highlighting the necessity to develop novel drugs or adjuvants. Given their critical and extensively regulatory role, TCS system has been proposed as a convincing target for novel drugs or adjuvants. PhoPQ TCS, a highly conserved TCS in several pathogens, plays crucial roles in low-magnesium adaption, polymyxin resistance, and virulence. In this study, we aimed to characterize the role of PhoPQ TCS of S. maltophilia in antibiotic susceptibility, physiology, stress adaptation, and virulence. RESULTS:To characterize PhoPQ system, phoP single mutant as well as phoP and phoQ double mutant were constructed. Distinct from most phoPQ systems of other microorganisms, two features were observed during the construction of phoP and phoQ single deletion mutant. Firstly, the phoQ mutant was not successfully obtained. Secondly, the compromised phenotypes of phoP mutant were not reverted by complementing an intact phoP gene, but were partially restored by complementing a phoPQ operon. Thus, wild-type KJ, phoP mutant (KJ?PhoP), phoPQ mutant (KJ?PhoPQ), and complemented strain (KJ?PhoPQ (pPhoPQ)) were used for functional assays, including antibiotic susceptibility, physiology (swimming motility and secreted protease activity), stress adaptation (oxidative, envelope, and iron-depletion stresses), and virulence to Caenorhabditis elegans. KJ?PhoPQ totally lost swimming motility, had enhanced secreted protease activity, increased susceptibility to antibiotics (?-lactam, quinolone, aminoglycoside, macrolide, chloramphenicol, and sulfamethoxazole/ trimethoprim), menadione, H2O2, SDS, and 2,2'-dipyridyl, as well as attenuated virulence to C. elegans. Trans-complementation of KJ?PhoPQ with phoPQ reverted these altered phenotypes to the wild-type levels. CONCLUSIONS:Given the critical and global roles of PhoPQ TCS in antibiotic susceptibility, physiology, stress adaptation, and virulence, PhoPQ is a potential target for the design of drugs or adjuvants.

Dataset Information

Clinical Features, Antibiotic Susceptibility Profile, and Outcomes of Infectious Keratitis Caused by Stenotrophomonas maltophilia.

Publications

Clinical Features, Antibiotic Susceptibility Profile, and Outcomes of Infectious Keratitis Caused by Stenotrophomonas maltophilia.

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