Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring

Ashizawa, Naoto; Tsuji, Yasuhiro; Kawago, Koyomi; Higashi, Yoshitsugu; Tashiro, Masato; Nogami, Makiko; Gejo, Ryuichi; Narukawa, Munetoshi; Kimura, Takeshi; Yamamoto, Yoshihiro

doi:10.1016/j.jiac.2015.11.012

Cited by 24 publications

(20 citation statements)

References 20 publications

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“…P‐gp inhibitors, such as omeprazole, amiodarone and amlodipine, were associated with the risk of linezolid overexposure . Conversely, P‐gp inducers, such as rifampin, levothyroxine and venlafaxine, were associated with that of underexposure . Unfortunately, in this study, we did not have the chance to retrieve data on patients’ comedications.…”

Section: Discussionmentioning

confidence: 92%

A 10‐Year Experience of Therapeutic Drug Monitoring (TDM) of Linezolid in a Hospital‐wide Population of Patients Receiving Conventional Dosing: Is there Enough Evidence for Suggesting TDM in the Majority of Patients?

Pea

Cojutti

Baraldo

2017

Basic Clin Pharma Tox

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A retrospective study was conducted to assess our 10-year experience of therapeutic drug monitoring (TDM) of linezolid in a large patient population to establish whether conventional dosing may result in adequate drug exposure in the majority of patients. Patients included in this study underwent TDM of linezolid trough concentration (C ) during treatment with conventional doses of 600 mg every 12 hr in the period between January 2007 and June 2016. The desired range of C was set between 2 and 7 mg/L (underexposure, C < 2 mg/L; overexposure, C > 7 mg/L). Multivariate logistic regression analysis investigated variables potentially correlated with linezolid C . One thousand and forty-nine patients had 2484 linezolid C assessed during treatment with conventional doses. Median (IQR) linezolid C was 5.08 mg/L (2.78-8.52 mg/L). Linezolid C was within the desired range in 50.8% of cases (1262/2484). Overexposure (n = 821; 33%) occurred much more frequently than underexposure (n = 401; 16.2%) and was severe (>20 mg/L) in 3.9% of cases (98/2484). Linezolid overexposure was significantly associated with CrCL estimates ≤40 mL/min. (OR 1.463; 95% CI 1.124-1.904, p = 0.005). Linezolid underexposure was significantly associated with CrCL estimates >100 mL/min. (OR 3.046; 95% CI 2.234-4.152, p < 0.001). Linezolid C was not correlated linearly with CrCL (R = 0.061). Variability in renal function explained only partially the very wide interindividual linezolid C variability. Our study suggests that TDM could represent a valuable approach in optimizing linezolid exposure in the majority of patients.

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Section: Discussionmentioning

confidence: 92%

A 10‐Year Experience of Therapeutic Drug Monitoring (TDM) of Linezolid in a Hospital‐wide Population of Patients Receiving Conventional Dosing: Is there Enough Evidence for Suggesting TDM in the Majority of Patients?

Pea

Cojutti

Baraldo

2017

Basic Clin Pharma Tox

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“…These results suggested that RFP pretreatment might reduce the permeability of LZD. On the other hand, there are some reports that RFP decreased the trough concentration of LZD in patients even in the case of intravenous LZD administration [ 26 , 27 ]. The reasons for these apparently conflicting results are unclear, though possible explanations include species differences and differences of clinical conditions, e.g.…”

Section: Discussionmentioning

confidence: 99%

Effect of coadministration of rifampicin on the pharmacokinetics of linezolid: clinical and animal studies

Hashimoto

Honda

Fujita

et al. 2018

J Pharm Health Care Sci

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BackgroundCombination therapy of linezolid (LZD) and rifampicin (RFP) may be more effective than monotherapy for treating gram-positive bacterial infections, but several studies have suggested that RFP decreases LZD exposures, thereby increasing the risk of therapeutic failure and emergence of LZD-resistant strains. However, the mechanism of the drug-drug interaction between LZD and RFP is unknown.MethodsWe conducted a prospective, open-label, uncontrolled clinical study in Japanese patients receiving LZD and RFP to evaluate the effect of coadministered RFP on the concentration of LZD. In animal study in rats, the influence of coadministered RFP on the pharmacokinetics of LZD administered intravenously or orally was examined. Intestinal permeability was investigated with an Ussing chamber to assess whether coadministered RFP alters the absorption process of LZD in the intestine.ResultsOur clinical study indicated that multiple doses of RFP reduced the dose-normalized trough concentration of LZD at the first assessment day by an average of 65%. In an animal study, we found that multiple doses of RFP significantly decreased the area under the concentration-time curve, the maximum concentration and the bioavailability of orally administered LZD by 48%, 54% and 48%, respectively. In contrast, the pharmacokinetics of intravenously administered LZD was unaffected by the RFP pretreatment. However, investigation of the intestinal permeability of LZD revealed no difference in absorptive or secretory transport of LZD in the upper, middle and lower intestinal tissues between RFP-pretreated and control rats, even though RFP induced gene expression of multidrug resistance protein 1a and multidrug resistance-associated protein 2.ConclusionsTherapeutic drug monitoring may be important for avoiding subtherapeutic levels of LZD in the combination therapy. The drug-drug interaction between LZD and RFP may occur only after oral administration of LZD, but is not due to any change of intestinal permeability of LZD.Trial registrationUMIN, UMIN000004322. Registered 4 October 2010.

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“…Till date, at least 11 types of SCC mec elements have been identified, and SCC mec I–V are predominant ( Ito et al, 2014 ). Rifampicin was used as an adjunctive therapy against biofilm or for the treatment of MRSA osteomyelitis ( Ashizawa et al, 2016 ; Yan et al, 2018 ); however, the burden of rifampicin-resistant and -intermediate S. aureus strains in China has been increasing ( Xiao et al, 2011 ). Mutations in rpoB , which encodes the β-subunit of RNA polymerase, are closely related to rifampicin resistance ( Bongiorno et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Prevalence and Characterization of Staphylococcus aureus Isolated From Women and Children in Guangzhou, China

et al. 2018

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The prevalent Staphylococcus aureus clones and antibiotic susceptibility profiles are known to change dynamically and geographically; however, recent S. aureus strains causing infections in women and children in China have not been characterized. In this study, we analyzed the molecular epidemiology and antimicrobial resistance of S. aureus isolated from patients in four centers for women and children in Guangzhou, China. In total, 131 S. aureus isolates (100 from children and 31 from women) were analyzed by spa typing, multi-locus sequence typing, virulence gene and antimicrobial resistance profiling, staphylococcal chromosomal cassette mec typing, and mutation analyses of rpoB. A total of 58 spa types, 27 sequence types (STs), and 10 clonal complexes (CCs) were identified. While CC59 (ST59-IV, 48.8%; ST338-III, 35.7%) and CC45 (ST45-IV, 100%) were the major clones (84.4%) among MRSA isolates, CC5 (ST188, 24.3%; ST1, 21.6%) and CC398 (ST398, 70%) were the major ones (70.1%) among MSSA isolates. ST338-MRSA-III mostly found in pus but hardly in respiratory tract samples while ST45-MRSA-IV was on the opposite, even though they both found in blood and cerebrospinal fluid sample frequently. Staphylococcal enterotoxin genes seb-seq-sek were strongly associated with ST59 and ST338, while sec was associated with ST45, ST121, ST22, and ST30. All ST338, ST1232, and SCCmec III isolates carried lukF/S-PV genes. A total of 80% of ST338 isolates were resistant to erythromycin, clindamycin, and tetracycline. All ST45 isolates exhibited intermediate or complete resistance to rifampicin. In total, 481 HIS/ASN mutations in rpoB were found in rifampicin-resistant or intermediate-resistant isolates. ST338-III and ST45-IV emerged as two of three major clones in MRSA isolates from women and children in Guangzhou, China, though ST59-MRSA-IV remained the most prevalent MRSA clone. Clonal distribution of S. aureus varied, depending on the specimen source. Virulence genes and antibiograms were closely associated with the clonal lineage. These results clarified the molecular epidemiology of S. aureus from women and children in Guangzhou, China, and provide critical information for the control and treatment of S. aureus infections.

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Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring

Cited by 24 publications

References 20 publications

A 10‐Year Experience of Therapeutic Drug Monitoring (TDM) of Linezolid in a Hospital‐wide Population of Patients Receiving Conventional Dosing: Is there Enough Evidence for Suggesting TDM in the Majority of Patients?

A 10‐Year Experience of Therapeutic Drug Monitoring (TDM) of Linezolid in a Hospital‐wide Population of Patients Receiving Conventional Dosing: Is there Enough Evidence for Suggesting TDM in the Majority of Patients?

Effect of coadministration of rifampicin on the pharmacokinetics of linezolid: clinical and animal studies

Prevalence and Characterization of Staphylococcus aureus Isolated From Women and Children in Guangzhou, China

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