Evaluation of the Synergistic Antibacterial Effects of Fosfomycin in Combination with Selected Antibiotics against Carbapenem–Resistant Acinetobacter baumannii

Nwabor, Ozioma Forstinus; Terbtothakun, Pawarisa; Chusri, Sarunyou

doi:10.3390/ph14030185

Cited by 19 publications

(16 citation statements)

References 50 publications

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“…A flow chart of the review is depicted in Figure 1 . Eighty-four relevant publications [ 12 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , ...…”

Section: Resultsmentioning

confidence: 99%

Systematic Review of Antimicrobial Combination Options for Pandrug-Resistant Acinetobacter baumannii

et al. 2021

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Antimicrobial combinations are at the moment the only potential treatment option for pandrug-resistant A. baumannii. A systematic review was conducted in PubMed and Scopus for studies reporting the activity of antimicrobial combinations against A. baumannii resistant to all components of the combination. The clinical relevance of synergistic combinations was assessed based on concentrations achieving synergy and PK/PD models. Eighty-four studies were retrieved including 818 eligible isolates. A variety of combinations (n = 141 double, n = 9 triple) were tested, with a variety of methods. Polymyxin-based combinations were the most studied, either as double or triple combinations with cell-wall acting agents (including sulbactam, carbapenems, glycopeptides), rifamycins and fosfomycin. Non-polymyxin combinations were predominantly based on rifampicin, fosfomycin, sulbactam and avibactam. Several combinations were synergistic at clinically relevant concentrations, while triple combinations appeared more active than the double ones. However, no combination was consistently synergistic against all strains tested. Notably, several studies reported synergy but at concentrations unlikely to be clinically relevant, or the concentration that synergy was observed was unclear. Selecting the most appropriate combinations is likely strain-specific and should be guided by in vitro synergy evaluation. Furthermore, there is an urgent need for clinical studies on the efficacy and safety of such combinations.

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Section: Resultsmentioning

confidence: 99%

Systematic Review of Antimicrobial Combination Options for Pandrug-Resistant Acinetobacter baumannii

et al. 2021

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“…The effect of gausemycin A in combination with other antibiotics was evaluated using the checkerboard technique with modifications (Nwabor et al, 2021 ). Briefly, 80 μL of diluted bacterial suspension (10 6 CFU/mL) was added to wells containing 10 μL of sub-inhibitory concentrations of gausemycin A and 10 μL of sub-inhibitory concentrations of conventional antibiotics.…”

Section: Methodsmentioning

confidence: 99%

Staphylococcus aureus is able to generate resistance to novel lipoglycopeptide antibiotic gausemycin A

et al. 2022

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Gausemycin A is the first member of the novel lipoglycopeptides family produced by Streptomyces roseoflavus INA-Ac-5812. Gausemycin A has a pronounced bactericidal activity against methicillin-resistant Staphylococcus aureus. However, the ability of S. aureus to be resistant to gausemycin A has not been investigated yet. Using serial passaging, we have obtained the resistant variant S. aureus 5812R, which is 80 times more resistant compared to the parent strain. Susceptibility testing of S. aureus 5812R revealed the acquisition of cross-resistance to daptomycin, cefazolin, tetracycline, and gentamicin, while the resistance to vancomycin, nisin, and ramoplanin was absent. Whole genome sequencing revealed single nucleotide polymorphism (SNP) and deletions in S. aureus 5812R, among which are genes encoding efflux pump (sepA), the two-component Kdp system (kdpE), and the component of isoprenoid biosynthesis pathway (hepT). Phenotypically, S. aureus 5812R resembles a small-colony variant, as it is slow-growing, forms small colonies, and is deficient in pigments. Profiling of fatty acids (FA) composition constituting the cytoplasmic membrane of S. aureus 5812R revealed the prevalence of anteiso-branched FA, while straight FA was slightly less present. The evidence also showed that the gausemycin A-resistant strain has increased expression of the cls2 gene of the cardiolipin synthase. The performed checkerboard assay pointed out that the combination of gausemycin A and ciprofloxacin showed a synergistic effect against S. aureus 5812R.

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“…148 Moreover, fosfomycin in tandem with either aminoglycosides or colistin or tigecycline presented synergistic effects against DTR A. baumannii. 149 However, the clinical potential of those combinations for the treatment of the infection due to DTR-GN pathogens remains unknown.…”

Section: Gram-negative Bacteriamentioning

confidence: 99%

Current Perspectives on the Diagnosis and Management of Healthcare-Associated Ventriculitis and Meningitis

Karvouniaris¹,

Brotis²,

Tsiakos³

et al. 2022

IDR

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Ventriculitis or post-neurosurgical meningitis or healthcare-associated ventriculitis and meningitis (VM) is a severe infection that complicates central nervous system operations or is related to the use of neurosurgical devices or drainage catheters. It can further deteriorate patients who have already presented significant neurologic injury and is associated with high morbidity, mortality, and poor functional outcome. VM can be difficult to distinguish from aseptic meningitis, inflammation that follows hemorrhagic strokes and neurosurgical operations. The associated microorganisms can be either skin flora or nosocomial pathogens, most commonly, Gram-negative bacteria. Classical microbiology can fail to isolate the culprit pathogen. Novel cerebrospinal fluid (CSF) biomarkers and molecular microbiology can fill the diagnostic gap and expedite pathogen identification and treatment. The pathogens may demonstrate significant resistant patterns and their antibiotic treatment can be difficult, as many important drug classes, including the beta-lactams and the glycopeptides, hardly penetrate to the CSF, and do not achieve therapeutic levels at the site of the infection. Treatment modifications, such as higher daily dose and prolonged or continuous administration, might increase antibiotic levels in the site of infection and facilitate pathogens clearance. However, in the case of therapeutic failure or infection due to difficultto-treat bacteria, the direct antibiotic instillation into the CSF, in addition to the intravenous antibiotic delivery, may help in the resolution of infection. However, intraventricular antibiotic therapy may result in aseptic meningitis and seizures, concerning the administration of aminoglycosides, polymyxins, and vancomycin. Meanwhile, bacteria form biofilms on the catheter or the device that should routinely be removed. Novel neurosurgical treatment modalities comprise endoscopic evacuation of debris and irrigation of the ventricles. VM prevention includes perioperative antibiotics, antimicrobial impregnated catheters, and the implementation of standardized protocols, regarding catheter insertion and manipulation.

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Evaluation of the Synergistic Antibacterial Effects of Fosfomycin in Combination with Selected Antibiotics against Carbapenem–Resistant Acinetobacter baumannii

Cited by 19 publications

References 50 publications

Systematic Review of Antimicrobial Combination Options for Pandrug-Resistant Acinetobacter baumannii

Systematic Review of Antimicrobial Combination Options for Pandrug-Resistant Acinetobacter baumannii

Staphylococcus aureus is able to generate resistance to novel lipoglycopeptide antibiotic gausemycin A

Current Perspectives on the Diagnosis and Management of Healthcare-Associated Ventriculitis and Meningitis

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