A 30-year-old man comes to the emergency department due to a week of fever, chills, and generalized malaise. The patient uses intravenous heroin and has been hospitalized several times due to skin and soft tissue infections. Cardiac auscultation shows a systolic ejection murmur, and subsequent echocardiography reveals a vegetative lesion of the aortic valve. Blood cultures from admission grow Enterococcus faecalis; subsequent testing reveals D-lactate rather than D-alanine as the terminal amino acid in the bacteria's pentapeptide peptidoglycan cell wall precursor. This substitution is likely to significantly decrease the efficacy of which of the following antibiotics?

Question

A 30-year-old man comes to the emergency department due to a week of fever, chills, and generalized malaise.  The patient uses intravenous heroin and has been hospitalized several times due to skin and soft tissue infections.  Cardiac auscultation shows a systolic ejection murmur, and subsequent echocardiography reveals a vegetative lesion of the aortic valve.  Blood cultures from admission grow Enterococcus faecalis; subsequent testing reveals D-lactate rather than D-alanine as the terminal amino acid in the bacteria's pentapeptide peptidoglycan cell wall precursor.  This substitution is likely to significantly decrease the efficacy of which of the following antibiotics?

Quizplus · Accepted Answer

11ec160b_3bf0_f0a1_9249_5182af9838ba_MD0001_00 The bacterial cell wall is composed of cross-linked peptidoglycan subunits on a backbone of N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG). Because cell wall disruption results in bacterial lysis, many antibiotics target cell wall synthesis, including the following: (Choice D) Polymyxin binds to lipopolysaccharide, leading to disruption of the bacterial cytoplasmic membrane. It does not interfere with the bacterial cell wall. (Choice E) Tetracycline binds to the 30S ribosomal subunit and prevents binding of aminoacyl-transfer RNAs. Resistance stems primarily from an efflux pump or alteration to the ribosome that allows translation to take place even when tetracycline is present. Educational objective: Vancomycin binds to the terminal D-alanine-D-alanine in bacterial pentapeptide peptidoglycan subunits, which prevents transpeptidase from binding to the pentapeptide, thereby inhibiting cell wall cross-linking. Resistance stems primarily from substitution of the terminal D-alanine with D-lactate, which prevents vancomycin binding. __________ References: Vancomycin-resistant enterococci. (http://www.ncbi.nlm.nih.gov/pubmed/11023964) Antibiotic resistance in bacteria and its future for novel antibiotic development. (http://www.ncbi.nlm.nih.gov/pubmed/16717405)

A 30-Year-Old Man Comes to the Emergency Department Due to a Week