Epidemiology and microbiology of severe community-acquired pneumonia in Central Australia: a retrospective study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) has high mortality and morbidity. AIMS: To describe the epidemiology and microbiology of SCAP in Central Australia. METHODS: A retrospective epidemiological study describing the characteristics, incidence rates (IR) and microbiological aetiology of SCAP in Central Australia. Adult patients admitted to Alice Springs Hospital Intensive Care Unit (ICU) between 2011 and 2014 that fitted the Infectious Diseases Society of America and American Thoracic Society definition of SCAP were included. Medical records were reviewed and compared between indigenous and non-indigenous patients. Primary outcomes were incidence rate and microbiological aetiology of SCAP. Secondary outcomes were 30-day mortality, and ICU and hospital length of stay (LoS). RESULTS: A total of 185 patents were included (156 indigenous; 29 non-indigenous). The overall SCAP IR per 1000 person-years was 3.24 (3.75 indigenous; 1.87 non-indigenous) with an IR difference of 2.71 after adjustment (P < 0.001). Those aged ≥50 years had an IR 74.8% higher than those younger. Male IR was 50% higher than females. There was a significant difference between indigenous and non-indigenous groups for age (48 vs 64 years), but not for 30-day mortality (7.7% vs 10.3%), ICU LoS (4.8 vs 4.6 days) and hospital LoS (10.9 vs 15.1 days) respectively. Likely causative pathogen(s) were identified in 117 patients; Streptococcus pneumoniae was the most common pathogen (28.2%), followed by Haemophilus influenzae (19.7%), Influenza A/B (16.2%) and Staphylococcus aureus (14.5%). CONCLUSION: A high incidence of SCAP was observed in Central Australia, disproportionately affecting the indigenous population. Prevention strategies are imperative, as well as early identification of SCAP and appropriate empiric antibiotic regimens.

Pharmacokinetics of Piperacillin in Critically Ill Australian Indigenous Patients with Severe Sepsis.

There are no available pharmacokinetic data to guide piperacillin dosing in critically ill Australian Indigenous patients despite numerous reported physiological differences. This study aimed to describe the population pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis. A population pharmacokinetic study of Indigenous patients with severe sepsis was conducted in a remote hospital intensive care unit. Plasma samples were collected over two dosing intervals and assayed by validated chromatography. Population pharmacokinetic modeling was conducted using Pmetrics. Nine patients were recruited, and a two-compartment model adequately described the data. The piperacillin clearance (CL), volume of distribution of the central compartment (Vc), and distribution rate constants from the central to the peripheral compartment and from the peripheral to the central compartment were 5.6 ± 3.2 liters/h, 14.5 ± 6.6 liters, 1.5 ± 0.4 h-1, and 1.8 ± 0.9 h-1, respectively, where CL and Vc were found to be described by creatinine clearance (CLCR) and total body weight, respectively. In this patient population, piperacillin demonstrated high interindividual pharmacokinetic variability. CLCR was found to be the most important determinant of piperacillin pharmacokinetics.

Optimising meropenem dosing in critically ill Australian Indigenous patients with severe sepsis.

Currently there are no pharmacokinetic (PK) data to guide antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis. This study aimed to determine whether the population pharmacokinetics of meropenem were different between critically ill Australian Indigenous and critically ill Caucasian patients. Serial plasma and urine samples as well as clinical and demographic data were collected over two dosing intervals from critically ill Australian Indigenous patients. Plasma meropenem concentrations were assayed by validated chromatography. Concentration-time data were analysed with data from a previous PK study in critically ill Caucasian patients using Pmetrics. The population PK model was subsequently used for Monte Carlo dosing simulations to describe optimal doses for these patients. Six Indigenous and five Caucasian subjects were included. A two-compartment model described the data adequately, with meropenem clearance and volume of distribution of the central compartment described by creatinine clearance (CLCr) and patient weight, respectively. Patient ethnicity was not supported as a covariate in the final model. Significant differences were observed for meropenem clearance between the Indigenous and Caucasian groups [median 11.0 (range 3.0-14.1) L/h vs. 17.4 (4.3-30.3) L/h, respectively; P <0.01]. Standard dosing regimens (1 g intravenous every 8 h as a 30-min infusion) consistently achieved target exposures at the minimum inhibitory concentration breakpoint in the absence of augmented renal clearance. No significant interethnic differences in meropenem pharmacokinetics between the Indigenous and Caucasian groups were detected and CLCr was found to be the strongest determinant of appropriate dosing regimens.

Total and unbound ceftriaxone pharmacokinetics in critically ill Australian Indigenous patients with severe sepsis.

In the absence of specific data to guide optimal dosing, this study aimed to describe the pharmacokinetics of ceftriaxone in severely septic Australian Indigenous patients and to assess achievement of the pharmacodynamic target of the regimens prescribed. A pharmacokinetic study was conducted in a remote hospital intensive care unit in patients receiving ceftriaxone dosing of 1 g every 12 h (q12h). Serial blood and urine samples were collected over one dosing interval on two consecutive days. Samples were assayed using a validated chromatography method for total and unbound concentrations. Concentration-time data collected were analysed with a non-compartmental approach. A total of 100 plasma samples were collected from five subjects. Ceftriaxone clearance, volume of distribution at steady-state, elimination half-life and elimination rate constant estimates were 0.9 (0.6-1.5) L/h, 11.2 (7.6-13.4) L, 9.5 (3.2-10.2) h and 0.07 (0.07-0.21) h-1, respectively. The unbound fraction of ceftriaxone ranged between 14% and 43%, with a higher unbound fraction present at higher total concentrations. The unbound concentrations at 720 min from the initiation of infusion for the first and second dosing intervals were 7.2 (4.8-10.7) mg/L and 7.8 (4.7-12.1) mg/L respectively, which exceeds the minimum inhibitory concentration of all typical target pathogens. In conclusion, the regimen of ceftriaxone 1 g q12h is adequate for critically ill Australian Indigenous patients with severe sepsis caused by non-resistant pathogens.

Community prevalence of methicillin and vancomycin resistant Staphylococcus aureus in and around Bangalore, southern India.

INTRODUCTION: Staphylococcus aureus is a known colonizer in humans and has been implicated in community acquired soft tissue infections. However emergence of methicillin resistant S. aureus(MRSA) has aroused great concern worldwide. This study aimed to determine the prevalence of MRSA in the community of Bangalore, southern India. METHODS: Swabs were collected from anterior nares, forearm, dorsum and palm of the hands of 1,000 healthy individuals residing in and around Bangalore, belonging to different socioeconomic strata and age groups. RESULTS: Analysis verified that 22.5% and 16.6% of the individuals presented Staphylococcus aureus and MRSA, respectively, at any of the three sites. Vancomycin resistance was observed in 1.4% of the S. aureus isolates, which was confirmed by detection of the vanA gene. It was interesting to note that 58.8% of the children in the age group 1-5 years-old presented MRSA, the highest percentage compared to other age groups of < 1 (44.4%) year-old, 5-20 (21.7%) years-old, > 40(11%) years-old and 20-40 (9.9%) years-old. Among the population of various socioeconomic strata, maximum MRSA colonization was observed among doctors (22.2%), followed by upper economic class (18.8%), lower economic class (17.7%), apparently healthy hospital in-patients (16.5%), nurses (16%) and middle economic class (12.5%). Most of the MRSA isolates were capsular polysaccharide antigen type 8 (57.1%). CONCLUSIONS: There is a need for continuous surveillance and monitoring of the presence of MRSA in the community and a clearer understanding of the dynamics of the spread of MRSA will assist in controlling its dissemination.

Community prevalence of methicillin and vancomycin resistant Staphylococcus aureus in and around Bangalore, southern India / Prevalência de Staphylococcus aureus resistente à meticilina e à vancomicina em comunidade no entorno de Bangalore, Índia do Sul

INTRODUCTION: Staphylococcus aureus is a known colonizer in humans and has been implicated in community acquired soft tissue infections. However emergence of methicillin resistant S. aureus (MRSA) has aroused great concern worldwide. This study aimed to determine the prevalence of MRSA in the community of Bangalore, southern India. METHODS: Swabs were collected from anterior nares, forearm, dorsum and palm of the hands of 1,000 healthy individuals residing in and around Bangalore, belonging to different socioeconomic strata and age groups. RESULTS: Analysis verified that 22.5 percent and 16.6 percent of the individuals presented Staphylococcus aureus and MRSA, respectively, at any of the three sites. Vancomycin resistance was observed in 1.4 percent of the S. aureus isolates, which was confirmed by detection of the vanA gene. It was interesting to note that 58.8 percent of the children in the age group 1-5 years-old presented MRSA, the highest percentage compared to other age groups of < 1 (44.4 percent) year-old, 5-20 (21.7 percent) years-old, > 40 (11 percent) years-old and 20-40 (9.9 percent) years-old. Among the population of various socioeconomic strata, maximum MRSA colonization was observed among doctors (22.2 percent), followed by upper economic class (18.8 percent), lower economic class (17.7 percent), apparently healthy hospital in-patients (16.5 percent), nurses (16 percent) and middle economic class (12.5 percent). Most of the MRSA isolates were capsular polysaccharide antigen type 8 (57.1 percent). CONCLUSIONS: There is a need for continuous surveillance and monitoring of the presence of MRSA in the community and a clearer understanding of the dynamics of the spread of MRSA will assist in controlling its dissemination.

INTRODUÇÃO: O Staphylococcus aureus é conhecido por ser um colonizador em humanos sendo implicado em infecções comunitárias dos tecidos moles. Contudo, a resistência à meticilina e emergência de S. aureus meticilina resistentes (MRSA) têm despertado preocupação em todo o mundo. O presente estudo visa encontrar a prevalência de MRSA na comunidade de Bangalore, sul da Índia. MÉTODOS: Suabes foram coletados de narinas anteriores, antebraço e dorso da palma de 1.000 indivíduos saudáveis, residentes em Bangalore e nas proximidades, pertencentes a diferentes estratos socioeconômicos e faixas etárias. RESULTADOS: Observou-se que 22,5 por cento e 16,6 por cento dos indivíduos foram abrigar Staphylococcus aureus e MRSA, respectivamente, em qualquer um dos três locais. Dos S. aureus isolados, 1,4 por cento também foram resistentes à vancomicina, o que foi confirmado pela detecção do gene vanA. Foi interessante notar que 58,8 por cento das crianças na faixa etária de 1-5 anos foram abrigar MRSA, o mais elevado em comparação com outros grupos etários de < 1 (44,4 por cento) ano, 50-20 (21,7 por cento) anos, > 40 (11 por cento) anos e 20-40 (9,9 por cento) anos. Entre a população de diferentes estratos socioeconômicos, a colonização de MRSA máxima foi observada entre os médicos (22,2 por cento), seguida pela classe econômica superior (18,8 por cento), classe baixa (17,7 por cento), pacientes aparentemente saudáveis (16,5 por cento), enfermeiros (16 por cento) e classe econômica média (12,5 por cento). A maioria dos MRSA isolados eram do tipo polissacarídeo capsular antígeno 8 (57,1 por cento). CONCLUSÕES: Há uma necessidade de vigilância e monitorização contínua da presença de MRSA na comunidade, bem como uma melhor compreensão da dinâmica de propagação de MRSA pode ajudar no controle da disseminação.