Daptomycin non-susceptible meticillin-resistant Staphylococcus aureus USA 300 isolate

Abstract

Daptomycin is a novel bactericidal agent active against Gram-positive pathogens including meticillin-resistant Staphylococcus aureus (MRSA). Our case is unique in the description of an MRSA USA 300 isolate that developed decreased susceptibility to daptomycin during daptomycin and vancomycin therapy. Directed sequencing detected a previously reported mutation in mprF, resulting in a T345A substitution, associated with non-susceptibility to daptomycin. Case reportA 40-year-old white male with a previous history of intravenous drug abuse and hepatitis C was admitted to a local hospital for fever and shortness of breath. He was empirically treated with intravenous vancomycin (1 g i.v. q.12 h) starting 11/11/2006 (dates in American format throughout). The first set of blood cultures drawn on the day of admission turned positive after 12 h incubation. A subsequent transoesophageal echocardiogram showed native aortic valve endocarditis.The first set of blood cultures grew meticillin-resistant Staphylococcus aureus (MRSA) with a vancomycin MIC of ¡2 mg ml 21 (Microscan; Dode-Behring). The patient had repeat blood cultures on 11/17/2006, which were persistently positive for MRSA (with blood cultures turning positive after 20 h incubation), after 5 days of vancomycin therapy. No serum vancomycin levels were available from the local hospital.Vancomycin was discontinued and intravenous daptomycin 6 mg kg 21 per day was started on 11/17/2006 at the local hospital. No baseline serum creatine phosphokinase level results were available. A computed tomography scan of the head to evaluate agitation revealed right temporal lesions, which were thought to be embolic in nature. The third set of repeat blood cultures dated 11/21/2006 also turned positive for MRSA after 12 h incubation.The patient was transferred to our facility on 11/24/2006 with persistent MRSA bacteraemia, aortic valve endocarditis and intracranial haemorrhagic septic emboli. On examination, he was found to be tachypnoeic and in moderate respiratory distress with a respiratory rate of 44 min 21 , pulse 131 beats min 21 , blood pressure 135/ 83 mmHg, temperature 37 u C and weight of 176 lbs. Laboratory results showed a white blood cell count of 2200 cells ml 21 , with 86 % polymorphonuclear leukocytes; a platelet count of 73 000 cells ml 21 ; blood urea nitrogen level of 52 mg dl 21 ; creatinine level of 2.2 mg dl 21 (baseline creatinine 1.4); and bicarbonate level of 14 mg dl 21 . His estimated creatinine clearance was 47.5 ml min 21 at the time of transfer.Chest X-ray showed a mild cardiomegaly with bilateral oedema and basilar opacities. The patient was later intubated for respiratory distress and airway protection. Review of the blood culture and susceptibility testing results (11/11, 11/17, 11/21) from the local hospital revealed that the MRSA isolates were susceptible to vancomycin with an MIC of ¡2 mg ml 21 . Daptomycin therapy was discontinued on the day of transfer, and vancomycin (15 mg kg 21 i.v. q.12 h) and gentamicin (1 mg kg 21 i.v. q.24 h) were initia...

Deciphering the tRNA-dependent lipid aminoacylation systems in bacteria: Novel components and structural advances

“…Several studies identified SNPs in the mprF gene of S. aureus clinical isolates, or laboratory strains evolved in vitro under antibiotic pressure. 72-83 Genome analysis revealed additional SNPs in genes such as rpoB (a polymerase subunit), capB (for capsular polysaccharide synthesis), and the promoter region of the dltABCD operon which is known to increase CAMP resistance (Fig. 2).…”

A Current Perspective on Daptomycin for the Clinical Microbiologist

“…Mutations in mprF, typically in the form of single-nucleotide polymorphisms, have been identified in most daptomycin-NS S. aureus strains investigated to date (88)(89)(90)(95)(96)(97)(98). In one study of a laboratory-derived daptomycin-NS S. aureus strain, mutation to mprF was shown, by array-based DNA hybridization and comparison, to consistently be the first genetic adaptation accompanying a daptomycin MIC of Ͼ1 g/ml (96).…”

“…A number of case reports have documented the emergence of daptomycin-NS S. aureus isolates during unsuccessful therapy with this agent (see Table S1 in the supplemental material) (76,(85)(86)(87)(88)(89)(90). In most instances, NS isolates emerged in the setting of recalcitrant, deep-seated infections and those associated with a high burden of the infecting organism, such as endocarditis, catheter-related bacteremia, or an undrained abscess (Table 2) (91).…”

What is MRSA?

“…This might be especially true for MRSA pneumonia, due to suboptimal penetration of vancomycin in the alveolar lining fluid [17]. Resistance to the newest antibiotics licensed to treat MRSA infections, linezolid and daptomycin has already emerged [18][19][20][21], although it is confined to a few cases. Therefore, the problem is two-fold: the therapeutic options to treat MRSA infections are limited and, in addition, MRSA also tends to acquire resistance to the newest antibiotics.…”