WBR0635

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Microbiology, MainCategory::Pharmacology
Sub Category	SubCategory::Infectious Disease
Prompt	[[Prompt::A 68-year-old woman with history of chronic obstructive pulmonary disease (COPD) presents for 2 days of purulent productive cough with fever and chills noted in the last 3 hours. You obtain a chest x-ray that confirms your suspicion of pneumonia and admit the patient for intravenous antibiotics. Despite empiric therapy, the patient continues to worsen over the next few days. Sputum cultures obtained on admission grow gram-positive cocci in clusters that show resistance to oxacillin. Which of the following antibiotics is contraindicated in this patient?]]
Answer A	AnswerA::Linezolid
Answer A Explanation	AnswerAExp::Linezolid is a first line therapy for CA-MRSA. There are no contraindications for its use in our patient.
Answer B	AnswerB::Daptomycin
Answer B Explanation	AnswerBExp::Daptomycin is contraindicated in CA-MRSA pneumonia since it is inactivated by the pulmonary surfactant.
Answer C	AnswerC::Vancomycin
Answer C Explanation	AnswerCExp::Vancomycin is a first line therapy for CA-MRSA. There are no contraindications for its use in our patient.
Answer D	AnswerD::Ceftaroline
Answer D Explanation	[[AnswerDExp::Ceftaroline is a new generation cephalosporin with broad spectrum and activity against MRSA. Recent clinical trials have shown that Ceftaroline is a good option for MRSA pneumonia, although its use is still not recommended by international guidelines.]]
Answer E	AnswerE::Clindamycin
Answer E Explanation	AnswerEExp::Clindamycin is a second line therapy for CA-MRSA pneumonia in patients that cannot for any reason receive vancomycin or linezolid.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Methicillin resistant Staphylococcus aureus (MRSA) has become an increasing concern not only for hospital acquired illnesses, but also in the community at large. Diagnosis of MRSA is usually made by documenting resistance to oxacillin or cefoxitin, as methicillin is no longer commercially available. Cefoxitin is a better inducer of the mecA gene, the gene responsible for resistance, than oxacillin. Tests that use cefoxitin usually demonstrate more accurate and reproducible results than tests with oxacillin. Resistance patterns of MRSA strains vary greatly especially when comparing community-acquired MRSA (CA-MRSA) to hospital-acquired MRSA (HA-MRSA). Generally, all community acquired strains are sensitive to vancomycin, linezolid, and daptomycin. High sensitivity rates are also reported to TMP/SMX, clindamycin, and doxycycline. In this patient, the presentation of MRSA pneumonia is by itself a contraindication for the use of daptomycin. Daptomycin is a lipopeptide used mostly in MRSA skin and soft-tissue infections but never in patients with CA-MRSA pneumonia. It binds to the membrane of gram-positive bacteria leading to membrane depolarization and cell death. In vitro studies have shown that daptomycin interacts with the pulmonary surfactant with leads to inhibition of its action. This is explained by the fact that the pulmonary surfactant is around 10% phosphatidylglycerol, an important part of the plasma membrane in gram-positive bacteria. Furthermore, RCTs have shown no benefit from the use of daptomycin in CA-MRSA pneumonia. For that, vancomycin and linezolid are the first line in pneumonia. Educational Objective: Silverman JA, Mortin LI, Vanpraagh AD, Li T, Alder J. Inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact. J Infect Dis. 2005;191(12):2149-52. References: Daptomycin is a lipopeptide antibiotic used in MRSA infections. It is inactivated by the pulmonary surfactant so it is contraindicated in MRSA pneumonia.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Daptomycin, WBRKeyword::MRSA, WBRKeyword::Pneumonia, WBRKeyword::Vancomycin, WBRKeyword::Antibiotics, WBRKeyword::Mechanism of action, WBRKeyword::Contraindications
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