β-Lactamase of <i>Pseudomonas pseudomallei</i> and its contribution to antibiotic resistance

Livemore, D. M.; Chau, Pui Hing; Wong, Alice I. W.; Leung, Y. K.

doi:10.1093/jac/20.3.313

Cited by 51 publications

(30 citation statements)

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“…Functionally, the most important of these is the BushJacoby-Medeiros class 2e beta-lactamase BPS-1, encoded by the gene blaA (or penA; Ambler class A), which hydrolyzes most cephalosporins but is readily inhibited by clavulanate (91,274). Acquired resistance to beta-lactam antibiotics while on treatment with a beta-lactam-beta-lactamase inhibitor combination or ceftazidime resulted from three distinct phenotypic changes: derepression of the chromosomal enzyme, an insensitivity to inhibition by beta-lactamase inhibitors, and a betalactamase specific for ceftazidime (169).…”

Section: Antibiotic Resistancementioning

confidence: 99%

Melioidosis: Epidemiology, Pathophysiology, and Management

2005

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Melioidosis, caused by the gram-negative saprophyte Burkholderia pseudomallei, is a disease of public health importance in southeast Asia and northern Australia that is associated with high case-fatality rates in animals and humans. It has the potential for epidemic spread to areas where it is not endemic, and sporadic case reports elsewhere in the world suggest that as-yet-unrecognized foci of infection may exist. Environmental determinants of this infection, apart from a close association with rainfall, are yet to be elucidated. The sequencing of the genome of a strain of B. pseudomallei has recently been completed and will help in the further identification of virulence factors. The presence of specific risk factors for infection, such as diabetes, suggests that functional neutrophil defects are important in the pathogenesis of melioidosis; other studies have defined virulence factors (including a type III secretion system) that allow evasion of killing mechanisms by phagocytes. There is a possible role for cell-mediated immunity, but repeated environmental exposure does not elicit protective humoral or cellular immunity. A vaccine is under development, but economic constraints may make vaccination an unrealistic option for many regions of endemicity. Disease manifestations are protean, and no inexpensive, practical, and accurate rapid diagnostic tests are commercially available; diagnosis relies on culture of the organism. Despite the introduction of ceftazidime- and carbapenem-based intravenous treatments, melioidosis is still associated with a significant mortality attributable to severe sepsis and its complications. A long course of oral eradication therapy is required to prevent relapse. Studies exploring the role of preventative measures, earlier clinical identification, and better management of severe sepsis are required to reduce the burden of this disease

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Section: Antibiotic Resistancementioning

confidence: 99%

Melioidosis: Epidemiology, Pathophysiology, and Management

2005

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“…Many reports have described successful treatment using a combination of ␤-lactam antibiotics and a ␤-lactamase inhibitor, such as amoxicillin plus clavulanic acid (19). Livermore, et al described a clavulanic acid-inhibitable ␤-lactam resistance phenotype of B. pseudomallei (13), and recently, the cloning of B. pseudomallei class A and D ␤-lactamases has been reported (4,14). Godfrey et al described three different phenotypes of clinical isolates from three patients which had undergone antibiotic treatment, and demonstrated that the resistance was due to derepressed ␤-lactamase production and structural mutations in the enzyme (10).…”

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confidence: 99%

Burkholderia pseudomallei Class A β-Lactamase Mutations That Confer Selective Resistance against Ceftazidime or Clavulanic Acid Inhibition

Tribuddharat

Moore

Baker

et al. 2003

Antimicrob Agents Chemother

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Burkholderia pseudomallei, the causative agent of melioidosis, is inherently resistant to a variety of antibiotics including aminoglycosides, macrolides, polymyxins, and ␤-lactam antibiotics. Despite resistance to many ␤-lactams, ceftazidime and ␤-lactamase inhibitor-␤-lactam combinations are commonly used for treatment of melioidosis. Here, we examine the enzyme kinetics of ␤-lactamase isolated from mutants resistant to ceftazidime and clavulanic acid inhibition and describe specific mutations within conserved motifs of the ␤-lactamase enzyme which account for these resistance patterns. Sequence analysis of regions flanking the B. pseudomallei penA gene revealed a putative regulator gene located downstream of penA. We have cloned and sequenced the penA gene from B. mallei and found it to be identical to penA from B. pseudomallei.Burkholderia pseudomallei is the causative agent of melioidosis, an endemic disease of Southeast Asia and Northern Australia (6). The severity of the disease can vary from asymptomatic infection to a severe form leading to acute sepsis and death. B. pseudomallei is a facultative intracellular pathogen which is able to survive inside phagocytic cells and thereby escape the host's humoral response. The disease can be reactivated after a very long remission (3,5,12). Currently, prolonged antibiotic treatment is advised to ensure complete eradication of the organism. Unfortunately, this practice creates a strong positive selection for antibiotic resistant strains resulting in many cases of treatment failure. Many reports have described successful treatment using a combination of ␤-lactam antibiotics and a ␤-lactamase inhibitor, such as amoxicillin plus clavulanic acid (19). Livermore, et al. described a clavulanic acid-inhibitable ␤-lactam resistance phenotype of B. pseudomallei (13), and recently, the cloning of B. pseudomallei class A and D ␤-lactamases has been reported (4, 14). Godfrey et al. described three different phenotypes of clinical isolates from three patients which had undergone antibiotic treatment, and demonstrated that the resistance was due to derepressed ␤-lactamase production and structural mutations in the enzyme (10). Here, we examine the B. pseudomallei penA gene encoding a class A ␤-lactamase in the clinical isolates of B. pseudomallei described by Godfrey et al. and from B. mallei ATCC 23344. We have identified point mutations in two of the isolates which likely account for their altered phenotypes. Finally, the enzyme kinetics of these mutants were compared to the wild type enzyme. MATERIALS AND METHODSBacterial strains and plasmids. The bacterial strains and plasmid used in this study are shown in Table 1. B. pseudomallei strains used in this study were collected from blood and urine samples from melioidosis patients both before and during antibiotic treatment at Sappasitprasong Hospital, Ubon Ratchatani, Thailand, between 1986 and 1989 and have been described previously (7, 10). All bacterial strains were grown at 37°C on Luria-Bertani (LB) agar or in LB broth. M...

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“…The new broad-spectrum quinolone antibiotics penetrate phagocytes well (32). In general, however, they have shown limited activity against P. pseudomallei in vitro (2,6,8,20,33,34 (22). The P-lactamase-producing strains in our study which were highly resistant to ticarcillin-clavulanate also had relatively high imipenem MICs (4 ,ug/ml).…”

Section: Discussionmentioning

confidence: 62%

“…Disk diffusion tests with 22 antibiotics were performed on 199 isolates of P. pseudomallei. These included 189 shiny, 6 mucoid, and 4 wrinkled yellow-to-white colony morphotypes of the organism.…”

Section: Resultsmentioning

confidence: 99%

Pseudomonas pseudomallei, a common pathogen in Thailand that is resistant to the bactericidal effects of many antibiotics

Sookpranee¹,

Sookpranee²,

Mellencamp³

et al. 1991

Antimicrob Agents Chemother

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The purpose of this investigation was to identify newer antimicrobial agents that may be useful in the therapy of melioidosis. The in vitro susceptibilities of 199 clinical isolates of Pseudomonas pseudomallei to 22 antibiotics were determined by standard disk diffusion, and those to 13 antibiotics were determined by agar dilution. Over 90% of the isolates were susceptible to imipenem, piperacillin-tazobactam, piperacillin, ceftazidime, ticarcillinclavulanate, ampicillin-sulbactam, and carumonam by both methods. Standard disk diffusion yielded unacceptably high false-susceptibility results with aztreonam, ciprofloxacin, and temafloxacin. Piperacillin, ceftazidime, imipenem, and ciprofloxacin were not bactericidal for three selected P. pseudomallei strains as determined by time-kill curve methods. Furthermore, addition of ciprofloxacin to piperacillin, ceftazidime, or imipenem did not enhance bactericidal activity. One hundred ninety-four strains showed weak P-lactamase production that did not increase upon incubation with cefoxitin. These findings suggest that several newer antimicrobial agents may prove useful in the treatment of melioidosis. However, results of susceptibility studies involving P. pseudomallei and newer agents must be interpreted with caution.

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β-Lactamase of Pseudomonas pseudomallei and its contribution to antibiotic resistance

Cited by 51 publications

References 0 publications

Melioidosis: Epidemiology, Pathophysiology, and Management

Melioidosis: Epidemiology, Pathophysiology, and Management

Burkholderia pseudomallei Class A β-Lactamase Mutations That Confer Selective Resistance against Ceftazidime or Clavulanic Acid Inhibition

Pseudomonas pseudomallei, a common pathogen in Thailand that is resistant to the bactericidal effects of many antibiotics

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