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Adjunctive rifampin for the treatment of Staphylococcus aureus bacteremia with deep infections: A meta-analysis.

ABSTRACT: BACKGROUND:Staphylococcus aureus (S. aureus) bacteremia (SAB) has high morbidity and mortality, with the development of methicillin-resistant S. aureus (MRSA) and the recognized shortcomings of vancomycin, its management is becoming more complicated. Considering the capability to penetrate cells, tissues and biofilms, rifampin has been used as adjunctive agent to against staphylococcal activity. OBJECTIVES:We performed this meta-analysis, aimed to explore the efficacy of adjunctive rifampin for the treatment of SAB. METHODS:Medical literatures were searched in the Pubmed, Medline, Embase and Cochrane databases up to October 2018. Patients with SAB received treatment with or without rifampin were included. The risk ratio (RR) and 95% confidence intervals (CI) of mortality, rate of bacteriological failure and relapse were estimated. RESULTS:Seven articles (five randomized controlled trials and two retrospective cohort studies) enrolling 979 and 636 patients of SAB treated with and without rifampin, respectively, were included. There was no difference of mortality between the adjunctive rifampin therapy and standard therapy on SAB (RR: 0.771, 95% CI: 0.442 to 1.347, I2 = 70.4%). In the subgroup analyses, the decreased mortality was observed in the adjunctive rifampin treatment for patients without MRSA infection (RR: 0.509, 95% CI: 0.372 to 0.697, I2 = 8.8%). In addition, there was no difference of the rate of bacteriologic failure (RR: 0.602, 95% CI: 0.198 to 1.825, I2 = 0.0%) or relapse (RR: 0.574, 95% CI: 0.106 to 3.112, I2 = 77.9%) between the adjunctive rifampin therapy and standard therapy on SAB. CONCLUSIONS:In general, insufficient evidence supported the efficacy of adjunctive use of rifampin for treatment of SAB, adding rifampin to standard therapy didn't decrease the incidence of death, rate of bacteriologic failure and relapse.

SUBMITTER: Ma H

PROVIDER: S-EPMC7082046 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Adjunctive rifampin for the treatment of Staphylococcus aureus bacteremia with deep infections: A meta-analysis.

Ma Huan H Cheng Jie J Peng Lengyue L Gao Yawen Y Zhang Guangli G Luo Zhengxiu Z

PloS one 20200319 3

<h4>Background</h4>Staphylococcus aureus (S. aureus) bacteremia (SAB) has high morbidity and mortality, with the development of methicillin-resistant S. aureus (MRSA) and the recognized shortcomings of vancomycin, its management is becoming more complicated. Considering the capability to penetrate cells, tissues and biofilms, rifampin has been used as adjunctive agent to against staphylococcal activity.<h4>Objectives</h4>We performed this meta-analysis, aimed to explore the efficacy of adjunctiv ...[more]

PMID: 32191760

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Project description:IntroductionClear cut-off levels could aid clinicians in identifying patients with a risk of fatal outcomes or complications such as deep infection foci in Staphylococcus aureus bacteremia (SAB). Cut-off levels for widely used clinical follow-up parameters including serum C-reactive protein (CRP) levels and white blood cell counts (WBC) have not been previously studied.Methods430 adult SAB patients in Finland took part in prospective multicentre study in which their CRP levels and WBC counts were measured on the day of the positive blood culture, every other day during the first week, twice a week during hospitalization and at 30 days. Receiver operating characteristic (ROC) analysis was used to evaluate the prognostic value of CRP and WBC on the day of the positive blood culture and at days 4, 7, and 14 in predicting mortality and the presence of deep infections at 30 days. Adjusted hazard ratios (HR) for CRP level and WBC count cut-off values for mortality were calculated by the Cox regression analysis and adjusted odds ratios (OR) for cut-off values to predict the presence of deep infection by the binary logistic regression analysis.ResultsThe succumbing patients could be distinguished from the survivors, starting on day 4 after the positive blood culture, by higher CRP levels. Cut-off values of CRP for day 30 mortality in adjusted analysis, that significantly predicted fatal outcome were at day 4 CRP >103 mg/L with sensitivity of 77%, specificity of 55%, and HR of 3.5 (95% CI, 1.2-10.3; p = 0.024), at day 14 CRP >61 mg/L with a sensitivity of 82%, specificity of 80% and HR of 3.6 (95% CI, 1.1-10.3; p<0.039) and cut-off value of WBC at day 14 >8.6 x109/L was prognostic with sensitivity of 77%, specificity of 78% and HR of 8.2 (95% CI, 2.9-23.1; p<0.0001). Cut-off values for deep infection in adjusted analysis were on the day of the positive blood culture CRP >108 mg/L with sensitivity of 77%, specificity of 60%, and HR of 2.6 (95% CI, 1.3-4.9; p = 0.005) and at day 14 CRP >22 mg/L with sensitivity of 59%, specificity of 68%, and HR of 3.9 (95% CI, 1.6-9.5; p = 0.003). The lack of decline of CRP in 14 days or during the second week were neither prognostic nor markers of deep infection focus.ConclusionsCRP levels have potential for the early identification of SAB patients with a greater risk for death and deep infections.

Project description:Effective antimicrobials are crucial for managing Staphylococcus aureus implant-associated bone infections (IABIs), particularly for infections due to rifampin-resistant S. aureus (RRSA). Failure to remove the implant results in persistent infection; thus, prolonged suppressive antibiotic therapy may be a reasonable alternative. However, a high incidence of adverse events can necessitate the discontinuation of therapy. In this scenario, commercial Staphylococcal bacteriophage Sb-1 combined with antibiotics is an option, showing a promising synergistic activity to facilitate the treatment of biofilm infections. Therefore, we evaluated the efficacy of the inhibitory activity of five antibiotics (doxycycline, levofloxacin, clindamycin, linezolid, and rifampin) alone or combined with phage Sb-1 (106 PFU/mL) in a simultaneous and staggered manner, to combat five clinical RRSA strains and the laboratory strain MRSA ATCC 43300 in 72 h by isothermal microcalorimetry. The synergistic effects were observed when phage Sb-1 (106 PFU/mL) combined with antibiotics had at least 2 log-reduction lower concentrations, represented by a fractional biofilm inhibitory concentration (FBIC) of <0.25. Among the antibiotics that we tested, the synergistic effect of all six strains was achieved in phage/doxycycline and phage/linezolid combinations in a staggered manner, whereas a distinctly noticeable improvement in inhibitory activity was observed in the phage/doxycycline combination with a low concentration of doxycycline. Moreover, phage/levofloxacin and phage/clindamycin combinations also showed a synergistic inhibitory effect against five strains and four strains, respectively. Interestingly, the synergistic inhibitory activity was also observed in the doxycycline-resistant and levofloxacin-resistant profile strains. However, no inhibitory activity was observed for all of the combinations in a simultaneous manner, as well as for the phage/rifampin combination in a staggered manner. These results have implications for alternative, combined, and prolonged suppressive antimicrobial treatment approaches.

Project description:Several management strategies may improve outcomes in patients with Staphylococcus aureus bacteremia.To review evidence of management strategies for S. aureus bacteremia to determine whether transesophageal echocardiography is necessary in all adult cases and what is the optimal antibiotic therapy for methicillin-resistant S. aureus (MRSA) bacteremia.A PubMed search from inception through May 2014 was performed to identify studies addressing the role of transesophageal echocardiography in S. aureus bacteremia. A second search of PubMed, EMBASE, and the Cochrane Library from January 1990 through May 2014 was performed to find studies addressing antibiotic treatment for MRSA bacteremia. Studies reporting outcomes from antibiotic therapy for MRSA bacteremia were included. All searches, which were limited to English and focused on adults, were augmented by review of bibliographic references from included studies. The quality of evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation system with consensus of independent evaluations by at least 2 of the authors.In 9 studies with a total of 4050 patients, use of transesophageal echocardiography was associated with higher rates of a diagnosis of endocarditis (14%-28%) compared with transthoracic echocardiography (2%-15%). In 4 studies, clinical or transthoracic echocardiography findings did not predict subsequent transesophageal echocardiography findings of endocarditis. Five studies identified clinical or transthoracic echocardiography characteristics associated with low risk of endocarditis (negative predictive values from 93% to 100%). Characteristics associated with a low risk of endocarditis include absence of a permanent intracardiac device, sterile follow-up blood cultures within 4 days after the initial set, no hemodialysis dependence, nosocomial acquisition of S. aureus bacteremia, absence of secondary foci of infection, and no clinical signs of infective endocarditis. Of 81 studies of antibiotic therapy for MRSA bacteremia, only 1 high-quality trial was identified. In that study of 246 patients with S. aureus bacteremia, daptomycin was not inferior to vancomycin or an antistaphylococcal penicillin, each in combination with low-dose, short-course gentamicin (clinical success rate, 44.2% [53/120] vs 41.7% [48/115]; absolute difference, 2.4% [95% CI, -10.2% to 15.1%]).All adult patients with S. aureus bacteremia should undergo echocardiography. Characteristics of low-risk patients with S. aureus bacteremia for whom transesophageal echocardiography can be safely avoided have been identified. Vancomycin and daptomycin are the first-line antibiotic choices for MRSA bacteremia. Well-designed studies to address the management of S. aureus bacteremia are needed.

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Adjunctive rifampin for the treatment of Staphylococcus aureus bacteremia with deep infections: A meta-analysis.

Publications

Adjunctive rifampin for the treatment of Staphylococcus aureus bacteremia with deep infections: A meta-analysis.

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