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Vancomycin plus nafcillin salvage for the treatment of persistent methicillin-resistant Staphylococcus aureus bacteremia following daptomycin failure: a case report and literature review.

ABSTRACT: Background:Evidence supporting beta-lactam plus vancomycin synergy for methicillin-resistant Staphylococcus aureus (MRSA) continues to grow. Current in vivo evidence demonstrates that combination therapy is associated with shorter time to blood sterilization than vancomycin monotherapy. However, this combination has not been reported as salvage therapy for persistent MRSA bacteremia. Case report:We report a case of an 81-year-old male who was successfully treated with vancomycin plus nafcillin after failing vancomycin monotherapy, daptomycin monotherapy, and daptomycin plus gentamicin combination therapy. The patient originally presented with sepsis from a suspected urinary tract infection. Blood cultures drawn on days 1, 3, 5, 15, 19, 23, and 28 remained positive for MRSA despite multiple antimicrobial therapy changes. On day 29, therapy was changed to vancomycin plus nafcillin. Blood cultures drawn on day 32 remained negative. After 11?days, nafcillin was changed to piperacillin-tazobactam due to an infected decubitus ulcer. The combination was continued for 42?days after achieving blood sterility, 71?days after the patient originally presented. Evidence regarding salvage therapy for persistent bacteremia is sparse and is limited to case reports and case series. Conclusion:This case report supports that vancomycin plus an anti-staphylococcal beta-lactam combination should be further studied as salvage therapy for persistent MRSA bacteremia.

SUBMITTER: Lewis PO

PROVIDER: S-EPMC6416679 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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Vancomycin plus nafcillin salvage for the treatment of persistent methicillin-resistant Staphylococcus aureus bacteremia following daptomycin failure: a case report and literature review.

Lewis Paul O PO Sevinsky Regan E RE Patel Paras D PD Krolikowski Matthew R MR Cluck David B DB

Therapeutic advances in infectious disease 20180910

<h4>Background</h4>Evidence supporting beta-lactam plus vancomycin synergy for methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) continues to grow. Current <i>in vivo</i> evidence demonstrates that combination therapy is associated with shorter time to blood sterilization than vancomycin monotherapy. However, this combination has not been reported as salvage therapy for persistent MRSA bacteremia.<h4>Case report</h4>We report a case of an 81-year-old male who was successfully treated wit ...[more]

PMID: 30891239

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Project description:The genomic evolution in vivo in persistent infection was critical information for understanding how methicillin-resistant Staphylococcus aureus (MRSA) was adapted to host environments with high antibiotic selective pressure. Thirty-two successive MRSA blood isolates with incremental non-susceptibility to vancomycin (VISA), daptomycin (DRSA), and/or linezolid (LRSA) were isolated from a patient failing multiple courses of antimicrobial therapy during 1,356 days of bacteremia. Whole genome sequencing (WGS) for all consecutive isolates were conducted to characterize the evolutionary pathways, resistance-associated mutations and their temporal relationship with antimicrobial treatment. The WGS-based phylogeny categorized the isogenic strains into three major clades, I (22 isolates), II (7 isolates), and III (3 isolates), respectively, harboring a median (range) of 7 (1-30), 62 (53-65), and 118 (100-130) non-synonymous mutations when compared to the very first isolate. Clade I strains were further grouped into early and late subclades, which, respectively, shared the most recent common ancestor with Clade III strains at day 393.7 and Clade II strain at day 662.5. Clade I and Clade III strains were characterized, respectively, with high rates of VISA (9/22, 40.9%) and VISA-and-DRSA phenotype (2/3, 66.7%). Linezolid-resistance including VISA-DRSA-and-LRSA phenotype was exclusively identified in Clade II strains after eight courses of linezolid treatment. The LRSA displayed a small colony variant phenotype and were associated with G2576T mutations in domain V region of 23S rRNA. Substantial loss of mobile elements or alleles mediating resistance or virulence were identified during the evolution of multi-resistance. However, the gene loss might not be correlated to the development of VISA, DRSA, or LRSA phenotype. In conclusion, MRSA in persistent bacteremia was adapted to harsh host environment through multiple pathways involving both resistance-associated mutations and extensive gene loss.

Project description:BACKGROUND:Vancomycin is the standard first-line treatment for methicillin-resistant Staphylococcus aureus bacteremia. However, recent consensus guidelines recommend that clinicians consider using alternative agents such as daptomycin when the vancomycin minimum inhibitory concentration is greater than 1 ug/ml. To date however, there have been no head-to-head randomized trials comparing the safety and efficacy of daptomycin and vancomycin in the treatment of such infections. The primary aim of our study is to compare the efficacy of daptomycin versus vancomycin in the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations (greater than or equal to 1.5 ug/ml) in terms of reducing all-cause 60-day mortality. METHODS/DESIGN:The study is designed as a multicenter prospective open label phase IIB pilot randomized controlled trial. Eligible participants will be inpatients over 21-years-old with a positive blood culture for methicillin-resistant Staphylococcus aureus with vancomycin minimum inhibitory concentration of greater than or equal to 1.5 ug/ml. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. We aim to recruit 50 participants over a period of two years. Participants randomized to the active control arm will receive vancomycin dose-while those randomized to the intervention arm will receive daptomycin. Participants will receive a minimum of 14 days study treatment.The primary analysis will be conducted on the intention-to-treat principle. The Fisher's exact test will be used to compare the 60-day mortality rate from index blood cultures (primary endpoint) between the two treatment arms, and the exact two-sided 95% confidence interval will be calculated using the Clopper and Pearson method. Primary analysis will be conducted using a two sided alpha of 0.05. DISCUSSION:If results from this pilot study suggest that daptomycin shows significant efficacy in the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations, we aim to proceed with a larger scale confirmatory study. This would help guide clinicians and inform practice guidelines on the optimal treatment for such infections. TRIAL REGISTRATION:The trial is listed on clinicaltrials.gov (NCT01975662, date of registration: 29 October 2013).

Dataset Information

Vancomycin plus nafcillin salvage for the treatment of persistent methicillin-resistant Staphylococcus aureus bacteremia following daptomycin failure: a case report and literature review.

Publications

Vancomycin plus nafcillin salvage for the treatment of persistent methicillin-resistant Staphylococcus aureus bacteremia following daptomycin failure: a case report and literature review.

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