In vitro laboratory and animal studies demonstrate a synergistic role for the combination of van... more In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and anti-staphylococcal β-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5g intravenously (IV) twice daily and were randomly assigned (1:1) to flucloxacillin 2g IV 6 hourly for seven days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. We randomly assigned 60 patients to receive vancomycin (n=29), or vancomycin plus flucloxacillin (n=31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval [CI] 41%, 102%; P=0.06) of that in the standard therapy group. There was no difference in the secondary endpoints of 28 and 90 day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. Combining an anti-staphylococcal β-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant endpoints are warranted.
Australia has among the world's lowest rates of tuberculosis (TB). However, it remains a lead... more Australia has among the world's lowest rates of tuberculosis (TB). However, it remains a leading global cause of morbidity and mortality. In Australia, TB remains more common in Indigenous than non-Indigenous Australians, and rates are rising among migrants, reflecting changing immigration patterns and rising rates in their homelands. This article reviews recent developments in TB of relevance to Australian general practice and provides an update of advances in the diagnosis and management of TB, and the role of the general practitioners in co-managing people with TB. First hand experience with imported multidrug resistant TB (MDR-TB) is increasing and is anticipated to rise in Australia. The reach of extensively drug resistant TB is also expanding. Although standard guidelines for management of drug susceptible TB remain unchanged, recent progress in the understanding, diagnosis and management of TB has occurred, driven by the need to respond to the challenges of MDR-TB and HIV...
Scrub typhus is recognised as an important differential diagnosis of fever, rash and sepsis in pa... more Scrub typhus is recognised as an important differential diagnosis of fever, rash and sepsis in patients with a history of travel to Litchfield National Park in the Top End of the Northern Territory. All confirmed scrub typhus cases to date from the Northern Territory have visited the Park, but the presence of similar rainforest pockets elsewhere in the Top End suggested further infectious locations might be identified with increased tourism. We report a case of serologically confirmed Orientia tsutsugamushi infection in a man who had not been within Litchfield Park, but had visited another discrete Top End rainforest area.
Three cases of severe necrotising fasciitis due to Vibrio vulnificus (two cases) and Vibrio parah... more Three cases of severe necrotising fasciitis due to Vibrio vulnificus (two cases) and Vibrio parahaemolyticus (one case, fatal), have occurred in Caucasian tourists while fishing at a remote tropical northern Australian estuarine area. Infections were acquired over a 4-year period during the tourist fishing season (April to July 2000-2003), when water temperatures range from 23 to 30 degrees C. They are notable for their geographical clustering in the remote western aspect of the Gulf of Carpentaria, an area characterised by sedimentary stratiform zinc-lead-silver deposits and a major mining operation. Patients presented with classical bullous cellulitis with necrotising fasciitis, accompanied by severe sepsis. Underlying risk factors were identified in each patient; in one instance, previously unrecognised haemochromatosis was diagnosed. Likely reasons for Vibrio occurrence in this particular ecological niche are discussed.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 2006
Endemic histoplasmosis occurs uncommonly in Australia and has not previously been reported in the... more Endemic histoplasmosis occurs uncommonly in Australia and has not previously been reported in the tropical Northern Territory, nor in Aboriginal Australian patients. We report one suspected and one confirmed case of severe disseminated histoplasmosis in Aboriginal Australians from the Northern Territory. Underlying illness included chronic cardiac disease and Type 1 diabetes mellitus, respectively, and neither patient was infected with HIV. The clinical presentations resembled malignancy. Diagnosis of histoplasmosis was made on the basis of bowel histology in Case 1, demonstrating characteristic yeasts, and lymph node histology and culture in Case 2. Histoplasmosis should be considered in relevant clinical situations, even in HIV-negative patients who have not left Australia.
Two cases of maternal to child transmission of melioidosis are reported from Australia's trop... more Two cases of maternal to child transmission of melioidosis are reported from Australia's tropical north. One infant died of overwhelming sepsis. Both lactating mothers had mastitis. In 1 case, Burkholderia pseudomallei isolated from breast milk was identical on pulsed-field gel electrophoresis with that in blood and cerebrospinal fluid isolates from the infant.
Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium ... more Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium tuberculosis drug resistance are poorly defined. Our objectives were to determine M. tuberculosis susceptibility and document management after receipt of susceptibility results. Methods. Prospective study of adult outpatients with smear-positive pulmonary tuberculosis (PTB) in Sabah, Malaysia. Additionally, hospital clinicians accessed the reference laboratory for clinical purposes during the study. Results. 176 outpatients were enrolled; 173 provided sputum samples. Mycobacterial culture yielded M. tuberculosis in 159 (91.9%) and nontuberculous Mycobacterium (NTM) in three (1.7%). Among outpatients there were no instances of multidrug resistant M. tuberculosis (MDR-TB). Seven people (4.5%) had isoniazid resistance (INH-R); all were switched to an appropriate second-line regimen for varying durations (4.5-9 months). Median delay to commencement of the second-line regimen was 13 weeks. Among 15 inpatients with suspected TB, 2 had multidrug resistant TB (one extensively drug resistant), 2 had INH-R, and 4 had NTM. Conclusions. Current community rates of MDR-TB in Sabah are low. However, INH-resistance poses challenges, and NTM is an important differential diagnosis in this setting, where smear microscopy is the usual diagnostic modality. To address INH-R management issues in our setting, we propose an algorithm for the treatment of isoniazid-resistant PTB.
Background Plasmodium vivax causes almost half of all malaria cases in Asia and is recognised as ... more Background Plasmodium vivax causes almost half of all malaria cases in Asia and is recognised as a significant cause of morbidity. In recent years it has been associated with severe and fatal disease. The extent to which P. vivax contributes to death is not known.MethodsTo define the epidemiology of mortality attributable to vivax malaria in southern Papua, Indonesia, a retrospective clinical records-based audit was conducted of all deaths in patients with vivax malaria at a tertiary referral hospital.ResultsBetween January 2004 and September 2009, hospital surveillance identified 3,495 inpatients with P. vivax monoinfection and 65 (1.9%) patients who subsequently died. Charts for 54 of these 65 patients could be reviewed, 40 (74%) of whom had pure P. vivax infections on cross-checking. Using pre-defined conservative criteria, vivax malaria was the primary cause of death in 6 cases, a major contributor in 17 cases and a minor contributor in a further 13 cases. Extreme anaemia was the most common primary cause of death. Malnutrition, sepsis with respiratory and gastrointestinal manifestations, and chronic diseases were the commonest attributed causes of death for patients in the latter two categories. There were an estimated 293,763 cases of pure P. vivax infection in the community during the study period giving an overall minimum case fatality of 0.12 per 1,000 infections. The corresponding case fatality in hospitalised patients was 10.3 per 1,000 infections.ConclusionsAlthough uncommonly directly fatal, vivax malaria is an important indirect cause of death in southern Papua in patients with malnutrition, sepsis syndrome and chronic diseases, including HIV infection.
BackgroundTuberculosis (TB) is generally well controlled in Malaysia, but remains an important pr... more BackgroundTuberculosis (TB) is generally well controlled in Malaysia, but remains an important problem in the nation¿s eastern states. In order to better understand factors contributing to high TB rates in the eastern state of Sabah, our aims were to describe characteristics of patients with TB at a large outpatient clinic, and determine the prevalence of HIV co-infection. Additionally, we sought to test sensitivity and specificity of the locally-available point-of-care HIV test kits.MethodsWe enrolled consenting adults with smear-positive pulmonary TB for a 2-year period at Luyang Clinic, Kota Kinabalu, Malaysia. Participants were questioned about ethnicity, smoking, prior TB, disease duration, symptoms and comorbidities. Chest radiographs were scored using a previously devised tool. HIV was tested after counselling using 2 point-of-care tests for each patient: the test routinely in use at the TB clinic (either Advanced Quality¿ Rapid Anti-HIV 1&2, FACTS anti-HIV 1/2 RAPID or HIV (...
Accurate diagnosis of acute rheumatic fever (ARF) remains problematic in high-incidence settings ... more Accurate diagnosis of acute rheumatic fever (ARF) remains problematic in high-incidence settings and especially in the Aboriginal population of Australia's Northern Territory. Previous investigators have demonstrated that strict application of the 1992 Updated Jones Criteria results in under-diagnosis. This study's objectives were to review use of the Jones Criteria (1992 Update) in diagnosing ARF in Australian Aboriginal patients presenting with suspected rheumatic fever, and formulate a locally relevant algorithm to improve diagnosis. Patients presenting to Royal Darwin Hospital with suspected ARF were prospectively assessed during a 15-month period. Demographic information, clinical history, examination, laboratory and echocardiographic findings were documented in order to determine whether the Jones Criteria were fulfilled, and to identify alternative diagnoses. The hospital discharge diagnosis was recorded and patients were followed up 18-33 months later. Out of 35 patients with suspected ARF, all were Aboriginal Australians, 17 (49%) had a discharge diagnosis of definite ARF, 7 (20%) had definite non-rheumatic fever diagnoses (disseminated gonococcal infection, systemic lupus erythematosis, buttock abscess and other febrile illnesses in children with cardiac murmur due to previously undiagnosed RHD). The remaining 11 (31%) posed diagnostic difficulties because of mild symptoms that failed to fulfil Jones Criteria (attracting diagnoses such as 'unexplained arthralgia') or atypical features such as older age. Two patients whose illness initially failed to fulfil the Jones Criteria, who were neither diagnosed with ARF nor commenced on secondary benzathine penicillin prophylaxis, were found on follow-up to have definite and probable ARF, respectively. At least 29% (8/28) of patients without prior recognised ARF/RHD had echocardiographic evidence of established RHD, indicating that previous episodes were missed. Individual mild episodes of ARF may be overlooked, with patients missing out on the timely institution of secondary prophylaxis. The Jones Criteria should be supplemented by active exclusion of differential diagnoses and vigilant follow-up including echocardiography. 'Probable' and 'possible ARF' should be recognised as diagnostic categories applying to patients not fulfilling the Jones Criteria but who nevertheless should be offered prophylactic penicillin at least until further follow-up. A set of diagnostic guidelines is proposed.
In vitro laboratory and animal studies demonstrate a synergistic role for the combination of van... more In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and anti-staphylococcal β-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5g intravenously (IV) twice daily and were randomly assigned (1:1) to flucloxacillin 2g IV 6 hourly for seven days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. We randomly assigned 60 patients to receive vancomycin (n=29), or vancomycin plus flucloxacillin (n=31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval [CI] 41%, 102%; P=0.06) of that in the standard therapy group. There was no difference in the secondary endpoints of 28 and 90 day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. Combining an anti-staphylococcal β-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant endpoints are warranted.
Australia has among the world's lowest rates of tuberculosis (TB). However, it remains a lead... more Australia has among the world's lowest rates of tuberculosis (TB). However, it remains a leading global cause of morbidity and mortality. In Australia, TB remains more common in Indigenous than non-Indigenous Australians, and rates are rising among migrants, reflecting changing immigration patterns and rising rates in their homelands. This article reviews recent developments in TB of relevance to Australian general practice and provides an update of advances in the diagnosis and management of TB, and the role of the general practitioners in co-managing people with TB. First hand experience with imported multidrug resistant TB (MDR-TB) is increasing and is anticipated to rise in Australia. The reach of extensively drug resistant TB is also expanding. Although standard guidelines for management of drug susceptible TB remain unchanged, recent progress in the understanding, diagnosis and management of TB has occurred, driven by the need to respond to the challenges of MDR-TB and HIV...
Scrub typhus is recognised as an important differential diagnosis of fever, rash and sepsis in pa... more Scrub typhus is recognised as an important differential diagnosis of fever, rash and sepsis in patients with a history of travel to Litchfield National Park in the Top End of the Northern Territory. All confirmed scrub typhus cases to date from the Northern Territory have visited the Park, but the presence of similar rainforest pockets elsewhere in the Top End suggested further infectious locations might be identified with increased tourism. We report a case of serologically confirmed Orientia tsutsugamushi infection in a man who had not been within Litchfield Park, but had visited another discrete Top End rainforest area.
Three cases of severe necrotising fasciitis due to Vibrio vulnificus (two cases) and Vibrio parah... more Three cases of severe necrotising fasciitis due to Vibrio vulnificus (two cases) and Vibrio parahaemolyticus (one case, fatal), have occurred in Caucasian tourists while fishing at a remote tropical northern Australian estuarine area. Infections were acquired over a 4-year period during the tourist fishing season (April to July 2000-2003), when water temperatures range from 23 to 30 degrees C. They are notable for their geographical clustering in the remote western aspect of the Gulf of Carpentaria, an area characterised by sedimentary stratiform zinc-lead-silver deposits and a major mining operation. Patients presented with classical bullous cellulitis with necrotising fasciitis, accompanied by severe sepsis. Underlying risk factors were identified in each patient; in one instance, previously unrecognised haemochromatosis was diagnosed. Likely reasons for Vibrio occurrence in this particular ecological niche are discussed.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 2006
Endemic histoplasmosis occurs uncommonly in Australia and has not previously been reported in the... more Endemic histoplasmosis occurs uncommonly in Australia and has not previously been reported in the tropical Northern Territory, nor in Aboriginal Australian patients. We report one suspected and one confirmed case of severe disseminated histoplasmosis in Aboriginal Australians from the Northern Territory. Underlying illness included chronic cardiac disease and Type 1 diabetes mellitus, respectively, and neither patient was infected with HIV. The clinical presentations resembled malignancy. Diagnosis of histoplasmosis was made on the basis of bowel histology in Case 1, demonstrating characteristic yeasts, and lymph node histology and culture in Case 2. Histoplasmosis should be considered in relevant clinical situations, even in HIV-negative patients who have not left Australia.
Two cases of maternal to child transmission of melioidosis are reported from Australia's trop... more Two cases of maternal to child transmission of melioidosis are reported from Australia's tropical north. One infant died of overwhelming sepsis. Both lactating mothers had mastitis. In 1 case, Burkholderia pseudomallei isolated from breast milk was identical on pulsed-field gel electrophoresis with that in blood and cerebrospinal fluid isolates from the infant.
Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium ... more Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium tuberculosis drug resistance are poorly defined. Our objectives were to determine M. tuberculosis susceptibility and document management after receipt of susceptibility results. Methods. Prospective study of adult outpatients with smear-positive pulmonary tuberculosis (PTB) in Sabah, Malaysia. Additionally, hospital clinicians accessed the reference laboratory for clinical purposes during the study. Results. 176 outpatients were enrolled; 173 provided sputum samples. Mycobacterial culture yielded M. tuberculosis in 159 (91.9%) and nontuberculous Mycobacterium (NTM) in three (1.7%). Among outpatients there were no instances of multidrug resistant M. tuberculosis (MDR-TB). Seven people (4.5%) had isoniazid resistance (INH-R); all were switched to an appropriate second-line regimen for varying durations (4.5-9 months). Median delay to commencement of the second-line regimen was 13 weeks. Among 15 inpatients with suspected TB, 2 had multidrug resistant TB (one extensively drug resistant), 2 had INH-R, and 4 had NTM. Conclusions. Current community rates of MDR-TB in Sabah are low. However, INH-resistance poses challenges, and NTM is an important differential diagnosis in this setting, where smear microscopy is the usual diagnostic modality. To address INH-R management issues in our setting, we propose an algorithm for the treatment of isoniazid-resistant PTB.
Background Plasmodium vivax causes almost half of all malaria cases in Asia and is recognised as ... more Background Plasmodium vivax causes almost half of all malaria cases in Asia and is recognised as a significant cause of morbidity. In recent years it has been associated with severe and fatal disease. The extent to which P. vivax contributes to death is not known.MethodsTo define the epidemiology of mortality attributable to vivax malaria in southern Papua, Indonesia, a retrospective clinical records-based audit was conducted of all deaths in patients with vivax malaria at a tertiary referral hospital.ResultsBetween January 2004 and September 2009, hospital surveillance identified 3,495 inpatients with P. vivax monoinfection and 65 (1.9%) patients who subsequently died. Charts for 54 of these 65 patients could be reviewed, 40 (74%) of whom had pure P. vivax infections on cross-checking. Using pre-defined conservative criteria, vivax malaria was the primary cause of death in 6 cases, a major contributor in 17 cases and a minor contributor in a further 13 cases. Extreme anaemia was the most common primary cause of death. Malnutrition, sepsis with respiratory and gastrointestinal manifestations, and chronic diseases were the commonest attributed causes of death for patients in the latter two categories. There were an estimated 293,763 cases of pure P. vivax infection in the community during the study period giving an overall minimum case fatality of 0.12 per 1,000 infections. The corresponding case fatality in hospitalised patients was 10.3 per 1,000 infections.ConclusionsAlthough uncommonly directly fatal, vivax malaria is an important indirect cause of death in southern Papua in patients with malnutrition, sepsis syndrome and chronic diseases, including HIV infection.
BackgroundTuberculosis (TB) is generally well controlled in Malaysia, but remains an important pr... more BackgroundTuberculosis (TB) is generally well controlled in Malaysia, but remains an important problem in the nation¿s eastern states. In order to better understand factors contributing to high TB rates in the eastern state of Sabah, our aims were to describe characteristics of patients with TB at a large outpatient clinic, and determine the prevalence of HIV co-infection. Additionally, we sought to test sensitivity and specificity of the locally-available point-of-care HIV test kits.MethodsWe enrolled consenting adults with smear-positive pulmonary TB for a 2-year period at Luyang Clinic, Kota Kinabalu, Malaysia. Participants were questioned about ethnicity, smoking, prior TB, disease duration, symptoms and comorbidities. Chest radiographs were scored using a previously devised tool. HIV was tested after counselling using 2 point-of-care tests for each patient: the test routinely in use at the TB clinic (either Advanced Quality¿ Rapid Anti-HIV 1&2, FACTS anti-HIV 1/2 RAPID or HIV (...
Accurate diagnosis of acute rheumatic fever (ARF) remains problematic in high-incidence settings ... more Accurate diagnosis of acute rheumatic fever (ARF) remains problematic in high-incidence settings and especially in the Aboriginal population of Australia's Northern Territory. Previous investigators have demonstrated that strict application of the 1992 Updated Jones Criteria results in under-diagnosis. This study's objectives were to review use of the Jones Criteria (1992 Update) in diagnosing ARF in Australian Aboriginal patients presenting with suspected rheumatic fever, and formulate a locally relevant algorithm to improve diagnosis. Patients presenting to Royal Darwin Hospital with suspected ARF were prospectively assessed during a 15-month period. Demographic information, clinical history, examination, laboratory and echocardiographic findings were documented in order to determine whether the Jones Criteria were fulfilled, and to identify alternative diagnoses. The hospital discharge diagnosis was recorded and patients were followed up 18-33 months later. Out of 35 patients with suspected ARF, all were Aboriginal Australians, 17 (49%) had a discharge diagnosis of definite ARF, 7 (20%) had definite non-rheumatic fever diagnoses (disseminated gonococcal infection, systemic lupus erythematosis, buttock abscess and other febrile illnesses in children with cardiac murmur due to previously undiagnosed RHD). The remaining 11 (31%) posed diagnostic difficulties because of mild symptoms that failed to fulfil Jones Criteria (attracting diagnoses such as 'unexplained arthralgia') or atypical features such as older age. Two patients whose illness initially failed to fulfil the Jones Criteria, who were neither diagnosed with ARF nor commenced on secondary benzathine penicillin prophylaxis, were found on follow-up to have definite and probable ARF, respectively. At least 29% (8/28) of patients without prior recognised ARF/RHD had echocardiographic evidence of established RHD, indicating that previous episodes were missed. Individual mild episodes of ARF may be overlooked, with patients missing out on the timely institution of secondary prophylaxis. The Jones Criteria should be supplemented by active exclusion of differential diagnoses and vigilant follow-up including echocardiography. 'Probable' and 'possible ARF' should be recognised as diagnostic categories applying to patients not fulfilling the Jones Criteria but who nevertheless should be offered prophylactic penicillin at least until further follow-up. A set of diagnostic guidelines is proposed.
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