Subtherapeutic Linezolid Concentrations in a Patient with Morbid Obesity and Methicillin-Resistant <i>Staphylococcus aureus</i> Pneumonia: Case Report and Review of the Literature

Muzevich, Katie M.; Lee, Kimberly B

doi:10.1345/aph.1r707

Cited by 24 publications

(12 citation statements)

References 38 publications

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“…However, in obese patients, observed serum levels have been lower than in the nonobese population, with one case report of a patient with a body mass index (BMI) of 37 describing clinical failure because of reduced serum concentration trough levels below the MIC 90 (MIC for 90% of the isolates) [69]. This suggests that there may be a need for increasing the dose in morbidly obese patients or in those >50% of their calculated ideal body weight [69][70][71].…”

Section: Linezolidmentioning

confidence: 99%

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Edwards

Andini

Esposito

et al. 2014

Journal of Global Antimicrobial Resistance

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Section: Linezolidmentioning

confidence: 99%

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Edwards

Andini

Esposito

et al. 2014

Journal of Global Antimicrobial Resistance

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“…There is limited evidence to guide dosing in obesity in the critically ill; however, published studies and case reports suggest higher doses of lipophilic antibacterials are required in this setting. 15,16 Reduced bacterial susceptibility For organisms with high MIC values, application of PK/PD models, increasing the total daily dose of the antibacterial with TDM (where applicable) should be considered.…”

Section: Loading Dose (Ld)mentioning

confidence: 99%

Pharmacokinetic considerations and dosing strategies of antibiotics in the critically ill patient

Shah

Barton

Fischer

2015

Journal of the Intensive Care Society

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The treatment of sepsis remains a significant challenge and is the cause of high mortality and morbidity. The pathophysiological alterations that are associated with sepsis can complicate drug dosing. Critical care patients often have capillary leak, increased cardiac output and altered protein levels which can have profound effects on the volume of distribution (Vd) and clearance (Cl) of antibacterial agents, both of which may affect the pharmacokinetics (PK) / pharmacodynamics (PD) of the drug. Along with antibacterial factors such as the hydrophilicity and its kill characteristics and the susceptibility and site of action of the microorganism, different dosing and administration strategies may be needed for the different drug classes. In conclusion, developing dosing and administration regimes of antibacterials that adhere to PK/PD principles increase antibacterial exposure. Tailoring therapy to the individual patient combined with TDM may contribute to improved clinical efficacy and contain the spread of resistance.

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“…Limited data on linezolid dosing in the morbidly obese population show lower serum drug concentrations than those in nonobese patients with potential treatment failure (Muzevich et al 2013 ). Two studies have shown increased clearance of linezolid and reduced serum concentration compared to population pharmacokinetic parameters, with trough levels below MIC 90 (Tsuji et al 2012a ;Stein et al 2005 ).…”

Section: Obese Patientsmentioning

confidence: 99%

PK/PD of Oxazolidinones

Theuretzbacher

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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Linezolid, the fi rst available compound in the group of oxazolidinones, provides an effective alternative for the treatment of multidrug-resistant (MDR) Gram-positive bacteria. Linezolid's iv and oral availability expands its usage to the outpatient setting. In vitro, animal, and clinical studies have defi ned an appropriate PK/PD index for linezolid, its correlation with the dosage regimen, and clinical outcome. Due to linezolid's wide interpatient variability, some patients may have increased risk of inadequate drug exposure. As these patients are not readily identifi ed, therapeutic drug monitoring may be necessary for critically ill patient populations as well as in long-term treatment. As alternative antibiotics are scarce, resistance development requires special attention. The selection of linezolid resistant mutants, especially with enterococci, and the emergence of mobile resistance determinants that affect a wide range of other ribosome-targeting antibiotics, will most likely spur the emergence and spread of linezolid resistance. Increasing drug exposure in an attempt to reduce selection pressure may not be feasible due to concentration dependent toxicity. On the other hand, combination therapy may positively impact exposure/resistance relationship, but our knowledge in this area remains incomplete. Employing PK/PD models to defi ne dosing strategies and using antibiotic combinations to reduce selection pressure on linezolid-resistant mutants are major tasks yet to be undertaken.

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Subtherapeutic Linezolid Concentrations in a Patient with Morbid Obesity and Methicillin-Resistant Staphylococcus aureus Pneumonia: Case Report and Review of the Literature

Abstract: To our knowledge, this is the first report of subtherapeutic linezolid concentrations correlated with decreased clinical effectiveness when during treatment of MRSA pneumonia in a patient with morbid obesity.

Cited by 24 publications

References 38 publications

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Pharmacokinetic considerations and dosing strategies of antibiotics in the critically ill patient

PK/PD of Oxazolidinones

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