Can intracellular Staphylococcus aureus in osteomyelitis be treated using current antibiotics? A systematic review and narrative synthesis

被引:59
作者
Zelmer, Anja R. [1 ]
Nelson, Renjy [2 ,3 ]
Richter, Katharina [4 ]
Atkins, Gerald J. [1 ]
机构
[1] Univ Adelaide, Fac Hlth & Med Sci, Ctr Orthopaed & Trauma Res, Adelaide, SA 5000, Australia
[2] Cent Adelaide Local Hlth Network, Dept Infect Dis, Adelaide, SA 5000, Australia
[3] Royal Adelaide Hosp, Adelaide, SA 5000, Australia
[4] Univ Adelaide, Basil Hetzel Inst Translat Hlth Res, Dept Surg, Richter Lab, Adelaide, SA 5011, Australia
关键词
SMALL-COLONY VARIANTS; PROSTHETIC JOINT INFECTIONS; FUSIDIC ACID; PHARMACODYNAMIC EVALUATION; IN-VITRO; STREPTOCOCCUS-PNEUMONIAE; LISTERIA-MONOCYTOGENES; DELIVERY-SYSTEM; DRUG-DELIVERY; CLINICAL-USE;
D O I
10.1038/s41413-022-00227-8
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Approximately 40% of treatments of chronic and recurrent osteomyelitis fail in part due to bacterial persistence. Staphylococcus aureus, the predominant pathogen in human osteomyelitis, is known to persist by phenotypic adaptation as small-colony variants (SCVs) and by formation of intracellular reservoirs, including those in major bone cell types, reducing susceptibility to antibiotics. Intracellular infections with S. aureus are difficult to treat; however, there are no evidence-based clinical guidelines addressing these infections in osteomyelitis. We conducted a systematic review of the literature to determine the demonstrated efficacy of all antibiotics against intracellular S. aureus relevant to osteomyelitis, including protein biosynthesis inhibitors (lincosamides, streptogramins, macrolides, oxazolidines, tetracyclines, fusidic acid, and aminoglycosides), enzyme inhibitors (fluoroquinolones and ansamycines), and cell wall inhibitors (beta-lactam inhibitors, glycopeptides, fosfomycin, and lipopeptides). The PubMed and Embase databases were screened for articles related to intracellular S. aureus infections that compared the effectiveness of multiple antibiotics or a single antibiotic together with another treatment, which resulted in 34 full-text articles fitting the inclusion criteria. The combined findings of these studies were largely inconclusive, most likely due to the plethora of methodologies utilized. Therefore, the reported findings in the context of the models employed and possible solutions for improved understanding are explored here. While rifampicin, oritavancin, linezolid, moxifloxacin and oxacillin were identified as the most effective potential intracellular treatments, the scientific evidence for these is still relatively weak. We advocate for more standardized research on determining the intracellular effectiveness of antibiotics in S. aureus osteomyelitis to improve treatments and patient outcomes.
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页数:18
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