The emergence of community-onset Clostridium difficile infection in a tertiary hospital in Singapore: a cause for concern.

Increasing rates of Clostridium difficile infection (CDI) among those without traditional risk factors have been reported mainly in Europe and North America. Here we describe the epidemiology, clinical features and ribotypes of CDI at National University Hospital (NUH), a 1000-bed tertiary care hospital in Singapore, from December 2011 to May 2012. All laboratory-confirmed CDI cases ≥21 years old who gave informed consent were included. Clinical data were collected prospectively and participants underwent an interviewer-administered questionnaire. Cases were classified by healthcare facility exposure and severity according to the SHEA guidelines. Included cases were also subjected to PCR and were classified by ribotype. In total, 66 patients participated in the study, of which 33 (50.0%) were healthcare-facility-associated hospital onset (HCFA-HO). Of the 33 community-onset (CO) cases, 14 (42.4%) were HCFA-CO, 10 (30.3%) were indeterminate and 9 (27.3%) were community-associated (CA). Of the CA cases, a majority (90.9%) had prior exposure to a healthcare facility within the last 12 weeks. Clinical characteristics, exposures and outcomes were not different between HO-CDI and CO-CDI. Diagnosis was delayed in CO-CDI compared with HO-CDI (4 days vs. 1 day; P=0.014). There was no difference in distribution of ribotypes between CO-CDI and HO-CDI, with 053 being most prevalent in both groups. CO-CDI increasingly contributes to the burden of CDI in NUH. This may reflect a trend in other parts of Asia. Healthcare professionals should be aware of the possible role of outpatient healthcare environments to CDI risk and thus extend control measures to outpatient settings.

Sustained meticillin-resistant Staphylococcus aureus control in a hyper-endemic tertiary acute care hospital with infrastructure challenges in Singapore.

BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) has been entrenched in Singapore hospitals since the 1980s, with an excess of 600 non-duplicate cases of infections (120 bacteraemia episodes) each year in our 995-bed university hospital. Approximately 5% of our hospital beds are used as isolation facilities. AIM: To study the impact of an MRSA control bundle that was implemented via gradual geographic extension across hospital wards. METHODS: The bundle included active surveillance on admission and transfer/discharge to identify ward-based acquisition of MRSA, isolation and cohorting of MRSA-infected patients, enhanced hand hygiene initiatives, and publicly displayed feedback of MRSA acquisition and hand hygiene compliance rates. Implementation was between October 2006 and June 2010 in order to provide lead-time for the incremental development of infrastructural capacity, and to develop an ethic of infection prevention among staff. Results were analysed via interrupted time-series analysis. FINDINGS: MRSA infections fell midway through the implementation, with MRSA bacteraemia declining from 0.26 [95% confidence interval (CI): 0.18-0.34] cases per 1000 inpatient-days in the first quarter of 2004 to 0.11 (95% CI: 0.07-0.19) cases per 1000 inpatient-days in the first quarter of 2012. MRSA acquisition rates fell a year after the programme had been fully implemented, whereas hand hygiene compliance rose significantly from 47% (95% CI: 44-49) in the first quarter of 2009 to 69% (95% CI: 68-71) in the first quarter of 2012. CONCLUSION: Successful staged implementation of an MRSA bundle in a hyper-endemic setting is sustainable and represents a model that may be adapted for similar settings.

Bad design, bad practices, bad bugs: frustrations in controlling an outbreak of Elizabethkingia meningoseptica in intensive care units.

BACKGROUND: Elizabethkingia meningoseptica is a nosocomial-adapted Gram-negative bacillus intrinsically resistant to antibiotics commonly used in the intensive care setting. An outbreak investigation commenced when five patients developed E. meningoseptica infection in two intensive care units (ICUs). METHODS: Analysis of laboratory data, case reviews, ICU workflows and extensive environmental sampling were undertaken. Molecular typing was performed using repetitive element palindromic polymerase chain reaction. Follow-up studies after interventions included environmental monitoring and a survey of staff compliance with interventions. FINDINGS: Laboratory data revealed increasing incidence of E. meningoseptica colonization or infection in ICU patients compared with preceding years. E. meningoseptica was cultured from 44% (35/79) of taps, but not from other sources. Hand hygiene sinks were used for disposal of patient secretions and rinsing re-usable patient care items. Sinks misused in this way were contaminated more often than sinks that were not misused (odds ratio 4.38, 95% confidence interval 1.68-11.39; P = 0.004). Molecular typing revealed that patient isolates had identical patterns to several isolates from hand hygiene taps. An urgent education programme was instituted to change these practices. Taps were cleaned systematically and aerators were changed. A temporary reduction in case numbers was achieved. Recolonization of taps was demonstrated on follow-up environmental screening, and cases recurred after two months. A survey revealed that 77.3% (163/213) of nursing staff still misused sinks due to time constraints or other problems adhering to the interventions. CONCLUSION: Introduction of non-sanctioned practices due to suboptimal unit design may have unintentional consequences for ICU patients. Room design and staff workflows must be optimized for patient safety as lapses in procedure can inadvertently put patients at risk.

Imipenem versus piperacillin/tazobactam for empiric treatment of neutropenic fever in adults.

Australian guidelines for neutropenic fever recommend piperacillin/tazobactam (PIP-TAZ) or cefepime for first-line empiric treatment of neutropenic fever. We compared outcomes among haematology patients before and after changing our first-line neutropenic fever treatment from imipenem to PIP-TAZ. Forty-five patients received imipenem and 60 PIP-TAZ. Despite a higher rate of antibiotic modification in the PIP-TAZ cohort, treatment success and time to defervescence were similar, with a trend towards fewer Clostridium difficile infections in the PIP-TAZ cohort.

Emergence of Klebsiella pneumoniae co-producing NDM-type and OXA-181 carbapenemases.

The emergence of carbapenemase-producing Enterobacteriaceae is a rapidly evolving threat worldwide. Here, we report the molecular characterization of two Klebsiella pneumoniae isolates carrying both bla(OXA -181) and bla(NDM -1) or bla(NDM -5) isolated from epidemiologically unrelated patients in Singapore. The bla(OXA -181) genes were found existing in different genetic environments.

Hot and steamy: outbreak of Bacillus cereus in Singapore associated with construction work and laundry practices.

BACKGROUND: A sudden increase in invasive infections caused by Bacillus cereus group organisms prompted an investigation at the National University Hospital in Singapore. AIM: To describe the investigation and management and subsequent difficulties controlling the outbreak. METHODS: Clinical case reviews were performed on all patients with B. cereus group recovered from clinical samples. Widespread environmental sampling was performed followed by review of hospital ventilation systems, domestic cleaning and laundry practices. FINDINGS: B. cereus was recovered from 171 patients during a six-month period coinciding with large-scale construction work beside the hospital. Most patients presented with bacteraemia (146/171; 85.4%) with 46/171 (26.9%) requiring extended treatment courses with vancomycin or other interventions. Sampling confirmed extensive airborne dispersal inside the hospital, including isolation rooms and air-conditioned wards. Hospital linen was heavily contaminated [7403 cfu/cm(2); 95% confidence interval (CI): 6349-8457; for 30 towels sampled], encouraged by inappropriate storage in airtight plastic bags (4437 cfu/cm(2); CI: 3125-5750) compared with storage in porous canvas bags (166 cfu/cm(2); CI: 76-256; P < 0.001). Interventions introduced included revision of laundry practices, transport and storage of hospital linen and towels; bleach-based environmental cleaning; and upgrading of ventilation systems throughout the hospital. Clinical case numbers returned to baseline levels within three months, only to rise again following relaxation of laundry practices. CONCLUSIONS: Construction work beside this Singapore hospital encouraged heavy contamination of air and environment with Bacillus spp., assumed to be responsible for the outbreak described. Failure to maintain revised laundry practices allowed resurgence of clinical cases, particularly among immunocompromised patients.

Immune reconstitution inflammatory syndrome associated with disseminated Mycobacterium sherrisii infection.

Mycobacterium sherrisii is a recently described mycobacterium closely related to Mycobacterium simiae. There have been only a few reports of this organism causing disease, predominantly in the setting of HIV with severe immunosuppression. We report the first case of disseminated M. sherrisii associated with immune reconstitution inflammatory syndrome.

Neurologic complications of surgery for anterior shoulder instability.

Two-hundred eighty-two patients underwent anterior reconstruction for recurrent glenohumeral instability between 1981 and 1991. Twenty-three patients (8.2%) had a neurologic deficit after surgery. Seven had sensory disturbances only; 16 had sensorimotor neuropathies (8 having multiple deficits designated as a diffuse plexopathy and 8 having a more defined deficit in 1 or 2 cords or peripheral nerves). Complete resolution occurred in 18 of the 23 patients. Four patients had a residual deficit (1 patient was lost to follow-up). Three had persistent sensory disturbances; 1 had permanent biceps weakness. None of these patients underwent surgical exploration. Older age (P = .045) and a Bankart lesion (P = .029) were associated with a neurologic complication. At an average follow-up of 8.7 years, 252 patients responded to a questionnaire regarding shoulder outcome, including 20 of the 23 patients with nerve injuries. The difference in the median Rowe score of those with and without nerve injury was not significant (P = .072). Neurologic injuries after anterior shoulder surgery presumably arise as a result of traction. The prognosis for neurologic recovery is generally good. Neurologic injury did not interfere with the outcome of the stabilization procedure.

Leptomeningeal carcinomatosis. Presenting features and prognostic factors.

OBJECTIVE: To determine factors that are predictive of survival among patients with leptomeningeal carcinomatosis. BACKGROUND: Studies of potential prognostic factors in leptomeningeal carcinomatosis have produced conflicting results. Reasons for the discrepancies may be methodological differences in case ascertainment, treatment protocols, and limitations due to the size of the study group. DESIGN AND METHODS: We reviewed the medical records of 126 patients with cytologically confirmed leptomeningeal carcinomatosis seen at the Mayo Clinic in Rochester, Minn, from 1983 to 1994. Clinical, radiographic, and cerebrospinal fluid (CSF) parameters at the time of presentation are summarized. Treatment response, complications, and cause of death are also discussed. Using the forward stepwise Cox model, independent predictors of survival were identified. RESULTS: Independent negative predictors of survival include elevated CSF protein (P < .001) and clinical involvement of the cerebral leptomeninges (P = .05). Independent positive predictors of survival were longer duration of neurological symptoms at the time of presentation (P < .005), treatment with intrathecal or intraventricular (intra-CSF) chemotherapy (P = .01), and female sex (P = .02). Other variables, including age, primary tumor type, and extent of systemic disease, were not predictive. CONCLUSIONS: We conclude that female sex, longer duration of neurological symptoms, absence of cerebral leptomeningeal clinical involvement, and absence of elevated CSF protein independently predict better survival. Patients treated with intra-CSF chemotherapy also survived longer.

Selective complexing of acetylcholinesterase in brain by intravenously administered monoclonal antibody.

Rats injected intravenously with monoclonal antibodies reactive with brain acetylcholinesterase (AChE) developed a prolonged depression of plasma AChE without changes in butyrylcholinesterase, lactic acid dehydrogenase, or hematocrit. One antibody, ZR1, accumulated in the brain and spinal cord. Within 3 days of injection, ZR1 bound to most of the AChE in cerebral cortex and certain other regions of the CNS. Examination of the molecular forms of cortical 10S AChE, whereas 4S AChE remained free. In vitro, however, ZR1 bound equally to solubilized 4S and 10S forms. These data provide direct evidence for the compartmentalization of different AChE forms in the CNS, 10S being mainly extracellular and 4S apparently intracellular. Development of a striking and persistent bilateral ptosis within hours of injection suggests that AChE in the autonomic nervous system is also accessible to antibodies and, furthermore, is the site of an immunopathological lesion. This novel model of cholinergic autoimmunity may have relevance for human neurological disorders of unknown etiology.

Quisqualate-sensitive, chloride-dependent transport of glutamate into rat brain synaptosomes.

A chloride-dependent transport process for glutamate has been identified in partially purified rat brain synaptosomes. This process shares many characteristics with the chloride-dependent sequestration process for glutamate in brain sonicates, which was previously thought to represent a quisqualate receptor, such as sensitivity to specific inhibitors and regulation by anions. Increasing the concentrations of chloride led to an increase in the apparent Vmax without affecting the KT. Synaptosomes preincubated with [3H]-L-glutamate exhibit an efflux of the radiolabel, which was stimulated by a substrate for the carrier in the incubating medium, indicating the bidirectional nature of the transport. The chloride-dependent transfer process is restricted to the brain, and regional and developmental profiles clearly distinguish it from the sodium-dependent high-affinity uptake process for glutamate. Nevertheless, the effects of excitotoxic lesions strongly suggest a neuronal localization of the chloride-dependent transport.

A simple method for quantitative electroencephalographic assessment of drugs with convulsant and anticonvulsant properties.

A simple, inexpensive and reliable microcomputer-assisted method to detect and quantify abnormal EEG spiking is described. High frequency wave forms (20-40 Hz) with high amplitude are discriminated using a beta-2 bandpass filter and a threshold comparater. The spikes are then compiled and reported by an Apple II+ microcomputer. The method was validated by measuring seizures generated by intraperitoneal injection of pentylenetetrazol (PTZ), by microinjection of excitatory amino acids into the dorsal hippocampus, and by the antagonism of these seizures by diazepam and 2-amino-7-phosphono heptanoic acid, respectively.