Detection of maternal transmission of resistant Gram-negative bacteria in a Cambodian hospital setting.

Infection with Extended-spectrum beta-lactamase -producing Enterobacterales (ESBL-E) is common in infants and leads to increased intensive care unit admission and mortality, but the role of maternal transmission in colonization of infants is unclear. Using paired isolates from 50 pairs of mothers and neonates admitted to a Cambodian hospital, we investigated antimicrobial resistance in Escherichia coli and Klebsiella pneumoniae using whole genome sequencing. We detected a wide variety of ESBL-E genes present in this population along with high levels of multidrug resistance. From 21 pairs where the same organism was present in both mother and neonate, we identified eight pairs with identical or near-identical isolates from both individuals suggestive of transmission at or around birth, including a pair with transmission of multiple strains. We found no evidence for transmission of plasmids only from mother to infant. This suggests vertical transmission outside hospitals as a common cause of ESBL-E colonization in neonates.

Occupational hazard in an immunosuppressed patient.

A 60-year-old male liver transplant recipient presented to his local hospital with left-sided partial seizures following a few days of generalised headache. He had undergone transplantation for primary sclerosing cholangitis 4 years earlier and maintained on tacrolimus monotherapy immunosuppression. He had no other comorbidities of note and worked as an arable farmer. At last follow-up, he had been well with preserved graft function and afternoon trough tacrolimus levels of 2-4 ng/mL. Over the preceding 4 weeks, he had been investigated locally for weight loss and a productive cough, where CT of the chest showed calcified mediastinal and hilar lymphadenopathy. Bronchoscopy samples were negative for acid-fast bacilli and he had been empirically treated for assumed community acquired pneumonia. Initial seizure management was with intravenous diazepam and phenytoin. On transfer to our centre, he was noted to be dysarthric with persisting 4/5 left upper limb weakness and nystagmus to all extremes of gaze. Blood tests were significant for mild anaemia (haemoglobin 90 g/L) and elevated C reactive protein (134 mg/L). The peripheral white cell count was 6.6×109/L. Biochemical liver graft function was normal and the 8am trough tacrolimus level was low at 2 ng/mL. CT head revealed bilateral ring enhancing cerebral lesions with surrounding vasogenic oedema but no mass effect. On MRI these exhibited restricted diffusion and marked perilesional oedema, suggestive of infection. Cerebrospinal fluid (CSF) analysis was as follows: white cell count <1/mm3, protein 0.57 g/L (normal range <45 g/L) and glucose 3 mmol/L (paired plasma glucose 4.8 mmol/L). Testing for virological causes via PCR, toxoplasma serology and blood and CSF cultures, including for tuberculosis, were all negative. Whole body positron emission tomography-CT demonstrated uptake in numerous peritoneal and intramuscular lesions as well as right-sided cervical lymphadenopathy, which was sampled with fine needle aspiration. Microscopy revealed a filamentous, beading and branching Gram-positive bacillus that was partially acid-fast, subsequently speciated as Nocardia farcinica.

Assessment of returning travellers with fever.

Millions of people travel to the tropics each year and a significant minority of them become ill, either during their stay or shortly after their return. Most have mild, self-limiting illnesses, but a few have a life-threatening condition. This article outlines how to evaluate fever in the returning traveller and discusses important infection control and public health measures. A detailed travel history, which takes into account travel destinations, specific activities and risk factors in relation to the onset of symptoms, is essential for constructing a comprehensive list of differential diagnoses and guiding appropriate investigations. Importantly, all travellers returning from the tropics with a fever should be investigated for malaria.

Prospective surveillance of healthcare associated infections in a Cambodian pediatric hospital.

BACKGROUND: Healthcare associated infections (HAI) are the most common preventable adverse events following admission to healthcare facilities. Data from low-income countries are scarce. We sought to prospectively define HAI incidence at Angkor Hospital for Children (AHC), a Cambodian pediatric referral hospital. METHODS: Prospective HAI surveillance was introduced for medical admissions to AHC. Cases were identified on daily ward rounds and confirmed using locally adapted Centers for Disease Control and Prevention (CDC) definitions. During the surveillance period, established infection prevention and control (IPC) activities continued, including hand hygiene surveillance. In addition, antimicrobial stewardship practices such as the creation of an antimicrobial guideline smartphone app were introduced. RESULTS: Between 1st January and 31st December 2015 there were 3,263 medical admissions and 102 HAI cases. The incidence of HAI was 4.6/1,000 patient-days (95% confidence interval 3.8-5.6) and rates were highest amongst neonates. Median length of stay was significantly longer in HAI cases: 25 days versus 5 days for non-HAI cases (p < 0.0001). All-cause in-hospital mortality increased from 2.0 to 16.1% with HAI (p < 0.0001). Respiratory infections were the most common HAI (54/102; 52.9%). Amongst culture positive infections, Gram-negative organisms predominated (13/16; 81.3%). Resistance to third generation cephalosporins was common, supporting the use of more expensive carbapenem drugs empirically in HAI cases. The total cost of treatment for all 102 HCAI cases combined, based on additional inpatient days, was estimated to be $299,608. CONCLUSIONS: Prospective HAI surveillance can form part of routine practice in low-income healthcare settings. HAI incidence at AHC was relatively low, but human and financial costs remained high due to increased carbapenem use, prolonged admissions and higher mortality rates.

Lack of Utility of Nasopharyngeal Swabs for Diagnosis of Burkholderia pseudomallei Pneumonia in Paediatric Patients.

Diagnosis of Burkholderia pseudomallei pneumonia in children is challenging. We investigated the utility of nasopharyngeal swabs taken from 194 paediatric patients on admission with radiologically proven pneumonia. Melioidosis was proven in 0.5% of samples tested and only in a third of those known to be bacteraemic with B. pseudomallei. It appears unlikely that culture of nasopharyngeal secretions is helpful to confirm B. pseudomallei pneumonia in paediatric patients.

Evidence for Community Transmission of Community-Associated but Not Health-Care-Associated Methicillin-Resistant Staphylococcus Aureus Strains Linked to Social and Material Deprivation: Spatial Analysis of Cross-sectional Data.

BACKGROUND: Identifying and tackling the social determinants of infectious diseases has become a public health priority following the recognition that individuals with lower socioeconomic status are disproportionately affected by infectious diseases. In many parts of the world, epidemiologically and genotypically defined community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged to become frequent causes of hospital infection. The aim of this study was to use spatial models with adjustment for area-level hospital attendance to determine the transmission niche of genotypically defined CA- and health-care-associated (HA)-MRSA strains across a diverse region of South East London and to explore a potential link between MRSA carriage and markers of social and material deprivation. METHODS AND FINDINGS: This study involved spatial analysis of cross-sectional data linked with all MRSA isolates identified by three National Health Service (NHS) microbiology laboratories between 1 November 2011 and 29 February 2012. The cohort of hospital-based NHS microbiology diagnostic services serves 867,254 usual residents in the Lambeth, Southwark, and Lewisham boroughs in South East London, United Kingdom (UK). Isolates were classified as HA- or CA-MRSA based on whole genome sequencing. All MRSA cases identified over 4 mo within the three-borough catchment area (n = 471) were mapped to small geographies and linked to area-level aggregated socioeconomic and demographic data. Disease mapping and ecological regression models were used to infer the most likely transmission niches for each MRSA genetic classification and to describe the spatial epidemiology of MRSA in relation to social determinants. Specifically, we aimed to identify demographic and socioeconomic population traits that explain cross-area extra variation in HA- and CA-MRSA relative risks following adjustment for hospital attendance data. We explored the potential for associations with the English Indices of Deprivation 2010 (including the Index of Multiple Deprivation and several deprivation domains and subdomains) and the 2011 England and Wales census demographic and socioeconomic indicators (including numbers of households by deprivation dimension) and indicators of population health. Both CA-and HA-MRSA were associated with household deprivation (CA-MRSA relative risk [RR]: 1.72 [1.03-2.94]; HA-MRSA RR: 1.57 [1.06-2.33]), which was correlated with hospital attendance (Pearson correlation coefficient [PCC] = 0.76). HA-MRSA was also associated with poor health (RR: 1.10 [1.01-1.19]) and residence in communal care homes (RR: 1.24 [1.12-1.37]), whereas CA-MRSA was linked with household overcrowding (RR: 1.58 [1.04-2.41]) and wider barriers, which represent a combined score for household overcrowding, low income, and homelessness (RR: 1.76 [1.16-2.70]). CA-MRSA was also associated with recent immigration to the UK (RR: 1.77 [1.19-2.66]). For the area-level variation in RR for CA-MRSA, 28.67% was attributable to the spatial arrangement of target geographies, compared with only 0.09% for HA-MRSA. An advantage to our study is that it provided a representative sample of usual residents receiving care in the catchment areas. A limitation is that relationships apparent in aggregated data analyses cannot be assumed to operate at the individual level. CONCLUSIONS: There was no evidence of community transmission of HA-MRSA strains, implying that HA-MRSA cases identified in the community originate from the hospital reservoir and are maintained by frequent attendance at health care facilities. In contrast, there was a high risk of CA-MRSA in deprived areas linked with overcrowding, homelessness, low income, and recent immigration to the UK, which was not explainable by health care exposure. Furthermore, areas adjacent to these deprived areas were themselves at greater risk of CA-MRSA, indicating community transmission of CA-MRSA. This ongoing community transmission could lead to CA-MRSA becoming the dominant strain types carried by patients admitted to hospital, particularly if successful hospital-based MRSA infection control programmes are maintained. These results suggest that community infection control programmes targeting transmission of CA-MRSA will be required to control MRSA in both the community and hospital. These epidemiological changes will also have implications for effectiveness of risk-factor-based hospital admission MRSA screening programmes.

Clonal variation in high- and low-level phenotypic and genotypic mupirocin resistance of MRSA isolates in south-east London.

OBJECTIVES: Both low-level mupirocin resistance (LMR) and high-level mupirocin resistance (HMR) have been identified. The aim of this study was to determine the epidemiology of LMR and HMR in MRSA isolates at five hospitals that have used mupirocin for targeted decolonization as part of successful institutional control programmes. METHODS: All MRSA identified in three microbiology laboratories serving five central and south-east London hospitals and surrounding communities between November 2011 and February 2012 were included. HMR and LMR were determined by disc diffusion testing. WGS was used to derive multilocus sequence types (MLSTs) and the presence of HMR and LMR resistance determinants. RESULTS: Prevalence of either HMR or LMR amongst first healthcare episode isolates from 795 identified patients was 9.69% (95% CI 7.72-11.96); LMR was 6.29% (95% CI 4.70-8.21) and HMR was 3.40% (95% CI 2.25-4.90). Mupirocin resistance was not significantly different in isolates identified from inpatients at each microbiology laboratory, but was more common in genotypically defined 'hospital' rather than 'community' isolates (OR 3.17, 95% CI 1.36-9.30, P = 0.002). LMR was associated with inpatient stay, previous history of MRSA and age ≥65 years; HMR was associated with age ≥65 years and residential postcode outside London. LMR and HMR varied by clone, with both being low in the dominant UK MRSA clone ST22 compared with ST8, ST36 and ST239/241 for LMR and with ST8 and ST36 for HMR. V588F mutation and mupA carriage had high specificity (>97%) and area under the curve (>83%) to discriminate phenotypic mupirocin resistance, but uncertainty around the sensitivity point estimate was large (95% CI 52.50%-94.44%). Mutations in or near the mupA gene were found in eight isolates that carried mupA but were not HMR. CONCLUSIONS: Mupirocin resistance was identified in <10% of patients and varied significantly by clone, implying that changes in clonal epidemiology may have an important role in determining the prevalence of resistance in conjunction with selection due to mupirocin use.

Assessment of returning travellers with fever.

Millions of people travel to the tropics each year and a significant minority of them become ill, either during their stay, or shortly after their return. Most have mild, self-limiting illnesses, but a few will have a life-threatening condition. This article outlines how to evaluate fever in the returning traveller and discusses important infection control and public health measures. A detailed travel history, which takes into account travel destinations, specific activities and risk factors in relation to the onset of symptoms, is essential for constructing a comprehensive list of differential diagnoses and guiding appropriate investigations. Importantly, all travellers returning from the tropics with a fever should be investigated for malaria, even if their return was 3 months ago or longer.

Short course amphotericin B with high dose fluconazole for HIV-associated cryptococcal meningitis.

OBJECTIVE: To define more rapidly effective initial antifungal regimens sustainable in resource-constrained settings. METHODS: Cohort study in SW Uganda: Thirty HIV-seropositive, antiretroviral therapy-naïve, patients with first episode cryptococcal meningitis were treated with high dose fluconazole (1200 mg/d for 2 weeks, then 800 mg/d until ART started) plus amphotericin B (AmB, 1 mg/kg/d), with routine normal saline and potassium supplementation, for the initial 5 days. Outcome measures were early fungicidal activity (EFA), determined by serial quantitative CSF cultures, safety, and mortality. RESULTS: EFA was -0.30 ± 0.11 log CFU/day calculated over the first 2 weeks of treatment, with no reduction in the rate of clearance between days 5 and 14. There was no grade IV hypokalemia or elevated creatinine, and no grade III or IV anemia or elevation of ALT. AmB or high dose fluconazole were not stopped early in any patient. Mortality was 23% at 2, and 28% at 10 weeks. CONCLUSIONS: Short course AmB was associated with rapid clearance of infection and was well-tolerated, suggesting it could be used safely in many centres currently relying on fluconazole monotherapy. Phase III trials are needed in African centres to compare short course with the standard 2-week course of AmB.