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Sharon J Peacock

Publications and source records attributed to Sharon J Peacock.

At least 37 records · Page 2Linked to original sources

In vitro motility of a population of clinical Burkholderia pseudomallei isolates.

Melioidosis, a serious infection caused by Burkholderia pseudomallei, is a leading cause of community-acquired sepsis in Northeast Thailand, and the commonest cause of death from community-acquired pneumonia in the Top End of Northern Australia. The causative organism is a Gram-negative, motile bacillus that is a facultative intracellular pathogen. B. pseudomallei flagella have been proposed as a possible vaccine candidate and putative virulence determinant. Flagella expression was highly conserved for 205 clinical B. pseudomallei isolates, as defined by in vitro swim and swarm motility assays. No association was found between motility and clinical factors including bacteremia and death.

Animals↗

Short report: Melioidosis in Myanmar: forgotten but not gone?

A serologic survey of adults resident in Myanmar was conducted to define the presence of antibodies to Burkholderia pseudomallei, the cause of melioidosis. Antibodies were detectable by indirect hemagglutination assay (IHA) in 757 (78%) of 968 adults, of whom 69 (7%) had an IHA titer > or =1:160.

Adult↗

Causes of community-acquired bacteremia and patterns of antimicrobial resistance in Vientiane, Laos.

There is no published information on the causes of bacteremia in the Lao PDR (Laos). Between 2000 and 2004, 4512 blood culture pairs were taken from patients admitted to Mahosot Hospital, Vientiane, Laos, with suspected community-acquired bacteremia; 483 (10.7%) cultures grew a clinically significant community-acquired organism, most commonly Salmonella enterica serovar typhi (50.9%), Staphylococcus aureus (19.0%), and Escherichia coli (12.4%). S. aureus bacteremia was common among infants (69.2%), while children 1-5 years had a high frequency of typhoid (44%). Multi-drug-resistant S. Typhi was rare (6%). On multiple logistic regression analysis, typhoid was associated with younger age, longer illness, diarrhea, higher admission temperature, and lower peripheral white blood cell count than non-typhoidal bacteremia. Empirical parenteral ampicillin and gentamicin would have some activity against approximately 88% of clinically significant isolates at a cost of US $1.4/day, an important exception being B. pseudomallei. Bacteremic infants in this setting require an anti-staphylococcal antibiotic.

Anti-Bacterial Agents↗

A hospital-based study of bloodstream infections in febrile patients in Dhulikhel Hospital Kathmandu University Teaching Hospital, Nepal.

The etiology of bloodstream infections in febrile patients remain poorly characterized in Nepal. A retrospective study of febrile patients presenting to Dhulikhel Hospital Kathmandu University Teaching Hospital from July 2002 to June 2004 was performed to evaluate the etiology of bloodstream infections and the drug sensitivity patterns of cultured organisms. The medical and laboratory records of all febrile patients with an axillary temperature > or = 38 degrees C who had a blood culture taken (n = 1,774) were retrieved and analyzed. Of these, 122 (6.9%) patients had positive blood cultures, of which 40.1% were age 11 to 20 years. The male to female ratio was 1.7:1. Antibiotics had been taken prior to hospital presentation by 39 (32%) patients. Salmonella enterica serovar Typhi and serovar Paratyphi A were isolated in 50 (41.0%) and 13 (10.7%) cases, respectively. All S. Typhi and S. Paratyphi isolates were susceptible to ceftriaxone, while susceptibility to ciprofloxacin and chloramphenicol was recorded in 94.8% and 94.5% of cases, respectively. Cephalexin and amoxicillin had the lowest rates of susceptibility (64.2% and 54.1%, respectively). Salmonella spp were usually sensitive to chloramphenicol. These findings provide clinicians in this region of Nepal with a better understanding of the spectrum of pathogens causing bloodstream infections and will help guide empiric antibiotic choice.

Adolescent↗

Rapid diagnosis of scrub typhus in rural Thailand using polymerase chain reaction.

The aim of this study was to evaluate the use of polymerase chain reaction (PCR) amplification of the O. tsutsugamushi 16S rRNA gene for the diagnosis of scrub typhus in rural Thailand. A prospective study of acute febrile illness in Udon Thani, northeast Thailand, identified 183 patients as having scrub typhus on the basis of immunofluorescent antibody testing (IFA) of paired sera. A further 366 febrile patients admitted concurrently with a range of other diagnoses acted as negative controls. Diagnostic sensitivity and specificity of 16S rRNA PCR was 44.8% and 99.7%, respectively, compared with IFA. PCR positivity was related to duration of symptoms and presence of eschar (P < 0.001, both cases). PCR using primers to amplify a fragment of the 56-kd gene had a sensitivity and specificity of 29.0% and 99.2%, respectively. PCR has a high specificity but low sensitivity for the rapid diagnosis of scrub typhus in this endemic setting.

Humans↗

Prospective evaluation of a rapid immunochromogenic cassette test for the diagnosis of melioidosis in northeast Thailand.

A prospective study was performed to compare a rapid immunochromogenic cassette test (ICT) with the indirect haemagglutination assay (IHA) and clinical rules for the diagnosis of melioidosis in an endemic area. The sensitivity and specificity of the IgG ICT was 86% and 47%, and the IgM ICT was 82% and 47%, respectively. These were similar to the results for IHA (sensitivity 73%, specificity 64%) and clinical rules (73% and 37%). ICT lacks clinical utility as a result of high background rates of positive Burkholderia pseudomallei serology in this population. Low sensitivity and specificity of clinical rules is consistent with the protean manifestations of melioidosis and clinical difficulty in identifying patients with melioidosis.

Adolescent↗

Two randomized controlled trials of ceftazidime alone versus ceftazidime in combination with trimethoprim-sulfamethoxazole for the treatment of severe melioidosis.

BACKGROUND: Two antibiotic regimens are used commonly in Thailand for the initial treatment of severe melioidosis: ceftazidime in combination with trimethoprim-sulfamethoxazole (TMP-SMX) and ceftazidime monotherapy. It is not known whether TMP-SMX provides an additional benefit. METHODS: Two prospective, randomized trials that compared these regimens for patients presenting with acute severe melioidosis were started independently at tertiary care hospitals in Ubon Ratchathani and Khon Kaen (in northeastern Thailand), and the results were analyzed together as a prospective, individual-patient data meta-analysis. The primary end point was in-hospital mortality rate. RESULTS: The in-hospital mortality rate among all enrolled patients (n=449) was not significantly different between those randomized to ceftazidime alone (25.1%; 56 of 223 subjects) and those randomized to ceftazidime with TMP-SMX (26.6%; 60 of 226 subjects; odds ratio [OR], 1.08; 95% confidence interval [CI], 0.7-1.7; stratified P=.73). Of the 241 patients with culture-confirmed melioidosis, 51 (21.2%) died. Of these 241 patients, 31 (12.9%) died > or =48 h after the time of study entry. Among patients with melioidosis, there was no difference in death rate between the 2 treatment groups for either all deaths (OR, 0.88; 95% CI, 0.48-1.6; stratified P=.70) or for deaths that occurred > or =48 h after hospital admission (OR, 0.88; 95% CI, 0.41-1.9; stratified P=.73). Conditional logistic regression analysis revealed that bacteremia, respiratory failure, and renal failure were independently associated with death and treatment failure. Drug regimens were not associated with death or treatment failure in this model. CONCLUSION: We conclude that the addition of TMP-SMX to ceftazidime therapy during initial treatment of severe melioidosis does not reduce the acute mortality rate.

Adult↗

Melioidosis in 6 tsunami survivors in southern Thailand.

BACKGROUND: Six cases of melioidosis were identified in survivors of the 26 December 2004 tsunami who were admitted to Takuapa General Hospital in Phangnga, a region in southern Thailand where melioidosis is not endemic. All 6 cases were associated with aspiration, and 4 were also associated with laceration. METHODS: We compared the clinical, laboratory, and radiographic findings and the outcomes for these 6 patients with those for 22 patients with aspiration-related melioidosis acquired during 1987-2003 in a melioidosis-endemic region in northeast Thailand. Results of tests for detection of Burkholderia pseudomallei in soil specimens from Phangnga and from northeast Thailand were compared. RESULTS: The 6 patients (age range, 25-65 years) presented with signs and symptoms of pneumonia 3-38 days (median duration, 6.5 days) after the tsunami. Chest radiograph findings at the onset of pneumonia were abnormal in all cases; 1 patient developed a lung abscess. B. pseudomallei was grown in blood cultures in 3 cases and in cultures of respiratory secretions in 4 cases. Two patients required ventilation and inotropes; 1 patient died. Compared with tsunami survivors, patients with aspiration-related melioidosis in northeast Thailand had a shorter interval (median duration, 1 day) between aspiration and onset of pneumonia; were more likely to exhibit shock, respiratory failure, renal failure, and/or altered consciousness (P=.03); and had a higher in-hospital mortality (64% [14 of 22 patients]; P=.07). These differences may be related to the severity of the near-drowning episode, the inhalation of sea water versus fresh water, the size of bacterial inoculum, and the possible acquisition (among tsunami survivors) of B. pseudomallei via laceration. Only 3 (0.8%) of 360 soil samples from Phangnga were positive for B. pseudomallei, compared with 26 (20%) of 133 samples from northeast Thailand (P<.0001). CONCLUSIONS: Tsunami survivors are at increased risk of melioidosis if they are injured in an environment containing B. pseudomallei.

Adult↗

Trimethoprim/sulfamethoxazole resistance in clinical isolates of Burkholderia pseudomallei.

OBJECTIVES: Trimethoprim/sulfamethoxazole is commonly used to treat melioidosis. Antimicrobial susceptibility testing using the disc diffusion method is commonly used in melioidosis-endemic areas, but may overestimate resistance to trimethoprim/sulfamethoxazole. PATIENTS AND METHODS: We performed disc diffusion and Etest on isolates from the first positive culture for all patients presenting to Sappasithiprasong Hospital, Ubon Ratchathani, Thailand, with culture-confirmed melioidosis between 1992 and 2003. RESULTS: The estimated resistance rate for 1976 clinical Burkholderia pseudomallei isolates was 13% by Etest and 71% by disc diffusion. All isolates classed as either susceptible (n=358) or as having intermediate resistance (n=218) on disc diffusion were susceptible by Etest. Only 258 of the 1400 (18%) isolates classed as resistant on disc diffusion were resistant by Etest. CONCLUSIONS: Disc diffusion testing of B. pseudomallei may be useful as a limited screening tool in resource poor settings. Isolates assigned as 'susceptible' or 'intermediate' by disc diffusion may be viewed as 'susceptible'; those assigned as 'resistant' require further evaluation by MIC methodology.

Anti-Infective Agents↗

Risk factors for hematogenous complications of intravascular catheter-associated Staphylococcus aureus bacteremia.

BACKGROUND: The role of both host and pathogen characteristics in hematogenous seeding following Staphylococcus aureus bacteremia is incompletely understood. METHODS: Consecutive patients with intravascular catheter-associated Staphylococcus aureus bacteremia were prospectively recruited over a 91-month period. The corresponding bloodstream isolates were examined for the presence of 35 putative virulence determinants. Patient and bacterial characteristics associated with the development of hematogenous complications (HCs) (i.e., septic arthritis, vertebral osteomyelitis, or endocarditis) were defined. RESULTS: HC occurred in 42 (13%) of 324 patients. Patient characteristics at diagnosis that were associated with HC included community onset (relative risk [RR], 2.25; 95% confidence interval [CI], 1.24-4.07; P=.007), increased symptom duration (odds ratio for each day, 1.14; 95% CI, 1.06-1.2; P<.001), presence of a long-term intravascular catheter or noncatheter prosthesis (RR, 4.02; 95% CI, 1.74-9.27; P<.001), hemodialysis dependence (RR, 3.84; 95% CI, 2.08-7.10; P<.001), and higher APACHE II score (P=.02). Bacterial characteristics included sea (RR, 2.03; 95% CI, 1.16-3.55; P=.011) and methicillin-resistant S. aureus (MRSA) (RR, 2.09; 95% CI, 1.19-3.67; P=.015). Subsequent failure to remove a catheter was also associated with HC (RR, 2.28; 95% CI, 1.22-4.27; P=.011). On multivariable analysis, symptom duration, hemodialysis dependence, presence of a long-term intravascular catheter or a noncatheter device, and infection with MRSA remained significantly associated with HC. CONCLUSIONS: This investigation identifies 4 host- and pathogen-related risk factors for hematogenous bacterial seeding and reaffirms the importance of prompt catheter removal.

Adult↗

Identification and preliminary characterization of cell-wall-anchored proteins of Staphylococcus epidermidis.

Staphylococcus epidermidis is a ubiquitous human skin commensal that has emerged as a major cause of foreign-body infections. Eleven genes encoding putative cell-wall-anchored proteins were identified by computer analysis of the publicly available S. epidermidis unfinished genomic sequence. Four genes encode previously described proteins (Aap, Bhp, SdrF and SdrG), while the remaining seven have not been characterized. Analysis of primary sequences of the Staphylococcus epidermidis surface (Ses) proteins indicates that they have a structural organization similar to the previously described cell-wall-anchored proteins from S. aureus and other Gram-positive cocci. However, not all of the Ses proteins are direct homologues of the S. aureus proteins. Secondary and tertiary structure predictions suggest that most of the Ses proteins are composed of several contiguous subdomains, and that the majority of these predicted subdomains are folded into beta-rich structures. PCR analysis indicates that certain genes may be found more frequently in disease isolates compared to strains isolated from healthy skin. Patients recovering from S. epidermidis infections had higher antibody titres against some Ses proteins, implying that these proteins are expressed during human infection. Western blot analyses of early-logarithmic and late-stationary in vitro cultures suggest that different regulatory mechanisms control the expression of the Ses proteins.

Bacterial Proteins↗

Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis.

Melioidosis (infection caused by Burkholderia pseudomallei) requires a prolonged course of oral antibiotics following initial intravenous therapy to reduce the risk of relapse after cessation of treatment. The current recommendation is a four-drug regimen (trimethoprim [TMP], sulfamethoxazole [SMX], doxycycline, and chloramphenicol) and a total treatment time of 12 to 20 weeks. Drug side effects are common; the aim of this study was to compare the efficacy and tolerance of the four-drug regimen with a three-drug regimen (TMP-SMX and doxycycline). An open-label, randomized trial was conducted in northeast Thailand. A total of 180 adult Thai patients were enrolled, of which 91 were allocated to the four-drug regimen and 89 to the three-drug regimen. The trial was terminated early due to poor drug tolerance, particularly of the four-drug regimen. The culture-confirmed relapse rates at 1 year were 6.6% and 5.6% for the four- and three-drug regimens, respectively (P = 0.79). The three-drug regimen was better tolerated than the four-drug regimen; 36% of patients receiving four drugs and 19% of patients receiving three drugs required a switch in therapy due to side effects (P = 0.01). The duration of oral therapy was significantly associated with relapse; after adjustment for confounders, patients receiving less than 12 weeks of oral therapy had a 5.7-fold increase of relapse or death. A combination of TMP-SMX and doxycycline is as effective as and better tolerated than the conventional four-drug regimen for the oral treatment phase of melioidosis.

Adolescent↗

Rapid immunofluorescence microscopy for diagnosis of melioidosis.

An immunofluorescent (IF) method that detects Burkholderia pseudomallei in clinical specimens within 10 min was devised. The results of this rapid method and those of an existing IF method were prospectively compared with the culture results for 776 specimens from patients with suspected melioidosis. The sensitivities of both IF tests were 66%, and the specificities were 99.5 and 99.4%, respectively.

Antigens, Bacterial↗

Comparison of Ashdown's medium, Burkholderia cepacia medium, and Burkholderia pseudomallei selective agar for clinical isolation of Burkholderia pseudomallei.

Ashdown's medium, Burkholderia pseudomallei selective agar (BPSA), and a commercial Burkholderia cepacia medium were compared for their abilities to grow B. pseudomallei from 155 clinical specimens that proved positive for this organism. The sensitivity of each was equivalent; the selectivity of BPSA was lower than that of Ashdown's or B. cepacia medium.

Agar↗

Recurrent melioidosis in patients in northeast Thailand is frequently due to reinfection rather than relapse.

Human melioidosis is associated with a high rate of recurrent disease, despite adequate antimicrobial treatment. Here, we define the rate of relapse versus the rate of reinfection in 116 patients with 123 episodes of recurrent melioidosis who were treated at Sappasithiprasong Hospital in Northeast Thailand between 1986 and 2005. Pulsed-field gel electrophoresis was performed on all isolates; isolates from primary and recurrent disease for a given patient different by one or more bands were examined by a sequence-based approach based on multilocus sequence typing. Overall, 92 episodes (75%) of recurrent disease were caused by the same strain (relapse) and 31 episodes (25%) were due to infection with a new strain (reinfection). The interval to recurrence differed between patients with relapse and reinfection; those with relapses had a median time to relapse of 228 days (range, 15 to 3,757 days; interquartile range [IQR], 99.5 to 608 days), while those with reinfection had a median time to reinfection of 823 days (range, 17 to 2,931 days; IQR, 453 to 1,211 days) (P = 0.0001). A total of 64 episodes (52%) occurred within 12 months of the primary infection. Relapse was responsible for 57 of 64 (89%) episodes of recurrent infection within the first year after primary disease, whereas relapse was responsible for 35 of 59 (59%) episodes after 1 year (P < 0.0001). Our data indicate that in this setting of endemicity, reinfection is responsible for one-quarter of recurrent cases. This finding has important implications for the clinical management of melioidosis patients and for antibiotic treatment studies that use recurrent disease as a marker for treatment failure.

Bacterial Typing Techniques↗

Role and significance of quantitative urine cultures in diagnosis of melioidosis.

Melioidosis is associated with significant mortality in countries in which it is endemic. Previous studies have demonstrated that quantitative Burkholderia pseudomallei counts in blood are predictive of mortality. Here we examine the relationship between outcomes and quantitative B. pseudomallei counts in urine. A total of 755 patients presenting to Sappasithiprasong Hospital, Ubon Ratchathani, northeast Thailand (in the northeast part of the country), with melioidosis between July 1993 and October 2003 had quantitative urine cultures performed within 72 h of admission. Urine culture results were divided into the following groups: (i) no growth of B. pseudomallei from a neat sample or pellet, (ii) positive result from a centrifuged pellet only (< 10(3) CFU/ml), (iii) detection of between 10(3) CFU/ml and 10(5) CFU/ml from a neat sample, or (iv) detection of > or = 10(5) CFU/ml from a neat sample. The overall in-hospital mortality rate was 45%. Patients with negative urine cultures had the lowest death rate (39%). Mortality rates rose with increasing B. pseudomallei counts in urine, from 58% for those with positive spun pellets only to 61% for those with between 10(3) CFU/ml and 10(5) CFU/ml and 71% for those with > or = 10(5) CFU/ml. This was independent of age, presence of bacteremia, known risk factors for melioidosis such as diabetes, and the prior administration of antibiotics. The presence of B. pseudomallei in urine during systemic infection is associated with a poor prognosis.

Burkholderia pseudomallei↗