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Current antimicrobial susceptibility of first-episode melioidosis Burkholderia pseudomallei isolates from the Northern Territory, Australia

https://doi.org/10.1016/j.ijantimicag.2014.04.012Get rights and content

Abstract

Burkholderia pseudomallei is a saprophytic Gram-negative bacterium responsible for the tropical infectious disease melioidosis. Melioidosis is endemic to northern Australia and Southeast Asia. In this study, 234 isolates of B. pseudomallei obtained from the first positive clinical specimen from 234 consecutive patients diagnosed with melioidosis between October 2009 and September 2012 were reviewed. All isolates were susceptible to meropenem and ceftazidime. In total, 226 isolates (96.6%) were susceptible to doxycycline and 232 (99.1%) were susceptible to trimethoprim/sulfamethoxazole (TMP/SMX; co-trimoxazole). Primary resistance of B. pseudomallei to ceftazidime and/or meropenem is exceedingly rare and clinicians can be confident in the current treatment guidelines for melioidosis. Whether the very low rates of TMP/SMX resistance seen in Australia reflect the global situation requires further studies using Etest, especially to clarify the rate of resistance in Thailand.

Introduction

Burkholderia pseudomallei is a Gram-negative bacterium that causes the clinical disease melioidosis. Melioidosis has diverse clinical manifestations including pneumonia, genitourinary infection often with prostatic abscess, septic arthritis and/or osteomyelitis, bacteraemia without a clinical focus, and cutaneous infection without sepsis [1]. As of 1 January 2014, the Darwin Prospective Melioidosis Study from the Northern Territory of Australia has documented 832 cases of melioidosis since it commenced in 1989, with 109 case fatalities (13.1%).

B. pseudomallei is intrinsically resistant to penicillin, ampicillin, first- and second-generation cephalosporins, gentamicin, tobramycin, macrolides and polymyxins [1], [2]. Consistent with international guidelines [1], melioidosis is treated in Darwin with intravenous ceftazidime for a minimum 2-week intensive phase, followed by a minimum 3-month eradication phase with oral trimethoprim/sulfamethoxazole (TMP/SMX; co-trimoxazole). Meropenem is generally reserved for patients admitted to the intensive care unit. If TMP/SMX is contraindicated, is not tolerated or causes clinically significant rash, renal impairment or bone marrow suppression, it is replaced with doxycycline. In Darwin, amoxicillin/clavulanic acid is reserved as a third-line eradication agent when TMP/SMX and doxycycline are unable to be used. Primary antimicrobial susceptibility of B. pseudomallei from the Darwin study was last reported in 2000, with 97% of isolates testing susceptible to the four antimicrobial agents in clinical use [3]. No isolates had primary resistance to ceftazidime or meropenem.

Section snippets

Materials and methods

In total, 234 B. pseudomallei isolates were obtained from the first positive clinical specimen from 234 patients consecutively diagnosed with melioidosis at Royal Darwin Hospital (Tiwi, NT, Australia) between October 2009 and September 2012. Isolates from eight additional cases were not available. Specimens included 121 blood cultures, 47 respiratory specimens, 19 wound swabs, 18 urines, 10 screening swabs (throat and rectal swabs placed into Ashdown's broth), 8 deep skin or soft-tissue abscess

Results

Using CLSI criteria, all 234 isolates of B. pseudomallei (100%) were susceptible to meropenem at MIC breakpoints of susceptible ≤4 μg/mL and resistant ≥16 μg/mL [isolate MIC interquartile range (IQR) 0.75–0.75 μg/mL]. Moreover, 234 isolates (100%) were susceptible to ceftazidime at MIC breakpoints of susceptible ≤8 μg/mL and resistant ≥32 μg/mL (isolate MIC IQR 1.5–1.5 μg/mL). Of the 234 isolates, 232 (99.1%) were susceptible to TMP/SMX at MIC breakpoints of susceptible ≤2/38 μg/mL and resistant ≥4/76 

Discussion

In this series of 234 consecutive clinical isolates of B. pseudomallei there was no primary resistance to ceftazidime and meropenem, the two antimicrobials used in the initial intensive phase of therapy, and only 1 isolate was resistant to TMP/SMX. Primary antimicrobial resistance in B. pseudomallei isolates from Darwin has not changed since last described 13 years ago [3]. The current data on primary antimicrobial susceptibility are comparable with data from Malaysia [7], [8], Brazil [9],

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