Nanotechnology using nanoscale materials is increasingly being utilized for clinical applications, especially as a new paradigm for infectious diseases. Infections caused by multidrug-resistant organisms (MDROs) are emerging as causes of morbidity and mortality worldwide. Antibiotic options for infections caused by MDROs are often limited. These clinical challenges highlight the critical demand for alternative and effective antimicrobial strategies. Nanoparticles (NPs) can penetrate the cell membrane of pathogenic microorganisms and interfere with important molecular pathways, formulating unique antimicrobial mechanisms. In combination with optimal antibiotics, NPs have demonstrated synergy and may aid in limiting the global crisis of emerging bacterial resistance. In this review, we summarized current research on the broad classification of the NPs that have shown in vitro antimicrobial activity against MDROs, including the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The pharmacokinetics and pharmacodynamic characteristics of NPs and bacteria-resistant mechanisms to NPs were also discussed.

Nanoparticles in the Treatment of Infections Caused by Multidrug-Resistant Organisms

External ventricular drains (EVDs) are commonly placed to monitor intracranial pressure and manage acute hydrocephalus in patients with a variety of intracranial pathologies. The indications for EVD insertion and their efficacy in the management of these various conditions have been previously addressed in guidelines published by the Brain Trauma Foundation, American Heart Association and combined committees of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. While it is well recognized that placement of an EVD may be a lifesaving intervention, the benefits can be offset by procedural and catheter-related complications, such as hemorrhage along the catheter tract, catheter malposition, and CSF infection. Despite their widespread use, there are a lack of high-quality data regarding the best methods for placement and management of EVDs to minimize these risks. Existing recommendations are frequently based on observational data from a single center and may be biased to the authors’ view. To address the need for a comprehensive set of evidence-based guidelines for EVD management, the Neurocritical Care Society organized a committee of experts in the fields of neurosurgery, neurology, neuroinfectious disease, critical care, pharmacotherapy, and nursing. The Committee generated clinical questions relevant to EVD placement and management. They developed recommendations based on a thorough literature review using the Grading of Recommendations Assessment, Development, and Evaluation system, with emphasis placed not only on the quality of the evidence, but also on the balance of benefits versus risks, patient values and preferences, and resource considerations.

The Insertion and Management of External Ventricular Drains: An Evidence-Based Consensus Statement : A Statement for Healthcare Professionals from the Neurocritical Care Society.

Septicaemia likely results in high case-fatality rates in the present multidrug-resistant (MDR) era. Amongst them are hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), two frequent fatal septicaemic entities amongst hospitalised patients. We reviewed the PubMed database to identify the common organisms implicated in HAP/VAP, to explore the respective risk factors, and to find the appropriate antibiotic choice. Apart from methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, extended-spectrum β-lactamase-producing Enterobacteriaceae spp., MDR or extensively drug-resistant (XDR)-Acinetobacter baumannii complex spp., followed by Stenotrophomonas maltophilia, Chryseobacterium indologenes, and Elizabethkingia meningoseptica are ranked as the top Gram-negative bacteria (GNB) implicated in HAP/VAP. Carbapenem-resistant Enterobacteriaceae notably emerged as an important concern in HAP/VAP. The above-mentioned pathogens have respective risk factors involved in their acquisition. In the present XDR era, tigecycline, colistin, and ceftazidime-avibactam are antibiotics effective against the Klebsiella pneumoniae carbapenemase and oxacillinase producers amongst the Enterobacteriaceae isolates implicated in HAP/VAP. Antibiotic combination regimens are recommended in the treatment of MDR/XDR-P. aeruginosa or A. baumannii complex isolates. Some special patient populations need prolonged courses (>7-day) and/or a combination regimen of antibiotic therapy. Implementation of an antibiotic stewardship policy and the measures recommended by the United States (US) Institute for Healthcare were shown to decrease the incidence rates of HAP/VAP substantially.

Epidemiology, Treatment, and Prevention of Nosocomial Bacterial Pneumonia

Objectives: To carry out a retrospective study on Acinetobacter baumannii isolates from various clinical samples in a tertiary care hospital in India and analyze its epidemiology, antibiotic susceptibility patterns, pathogenic potential and nosocomial status. 	Materials and methods: The clinical specimens over a period of 14 months from December 2008 to January 2010 were analyzed and the A.baumannii isolates obtained by an automated identification system (Vitek 2 Compact) were segregated for further study. Their antibiograms were studied and a clinical correlation was made to assess their pathogenic status and mode of acquisition. Further, the nosocomial infections acquired during this period were studied and the contribution made by A.baumannii was calculated to assess its nosocomial status. 	Results: A.baumannii was isolated in 155 samples out of 1632 gram negative isolates (9.4% prevalence) from the entire hospital. Maximum isolates were from respiratory secretions (57.4%) followed by blood (23.8%). Prevalence of A.baumannii rose to 22.7% (119 out of 525) in intensive care unit (ICU) and 65 isolates (54.6%) proved to be pathogenic. A.baumannii contributed to 30.4% ventilator associated pneumonia, 35.2% Catheter Associated Blood Stream Infections, 12.5% Surgical Site Infections and 2.94% Catheter Associated Urinary Tract Infections. Overall resistance of A.baumannii towards carbapenems was 90% from all hospital isolates. ICU isolates showed higher resistance (93.2%) as compared to Inpatient Department (82.7%) and Out-patient Department (57.1%). 	Conclusion: In this study, A.baumannii isolates showed a pathogenic potential of around 54.6% and a majority were found to be carbapenem resistant. We must be cognizant of the fact that all A.baumannii isolations doesn\'t necessarily mean infection and antibiotics should only be given in clinically proven infections.

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Acinetobacter baumannii isolates in a tertiary care hospital: Antimicrobial resistance and clinical significance

There is a pressing need to understand better the extent and distribution of antimicrobial resistance on a global scale, to inform development of effective interventions. Collation of datasets for meta-analysis, mathematical modelling and temporo-spatial analysis is hampered by the considerable variability in clinical sampling, variable quality in laboratory practice and inconsistencies in antimicrobial susceptibility testing and reporting. The Microbiology Investigation Criteria for Reporting Objectively (MICRO) checklist was developed by an international working group of clinical and laboratory microbiologists, infectious disease physicians, epidemiologists and mathematical modellers. In keeping with the STROBE checklist, but applicable to all study designs, MICRO defines items to be included in reports of studies involving human clinical microbiology data. It provides a concise and comprehensive reference for clinicians, researchers, reviewers and journals working on, critically appraising, and publishing clinical microbiology datasets. Implementation of the MICRO checklist will enhance the quality and scientific reporting of clinical microbiology data, increasing data utility and comparability to improve surveillance, grade data quality, facilitate meta-analyses and inform policy and interventions from local to global levels.

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Microbiology Investigation Criteria for Reporting Objectively (MICRO): a framework for the reporting and interpretation of clinical microbiology data.

Background With increasing prevalence and spread of multidrug resistant Gram-negative infections, parenteral polymyxins resurged in clinical practice. The primary aim of the study was to determine the predictors of treatment failure and in-hospital mortality among critically ill patients treated with polymyxin B. Methods Demographic data, underlying diseases, procedures and details on polymyxin B therapy were retrospectively analyzed in a cohort of 84 patients who received intravenous polymyxin B in an intensive care unit from 2010 to 2014. Results Polymyxin B was used to treat bacteremia (46.4% of cases) and pneumonia (53.6%). Majority of the pathogens isolated were Acinetobacter spp. (96.4%). The mortality rate was 48.8%, of which 82.9% was attributed to polymyxin B treatment failure. The independent predictors of treatment failure were low doses of polymyxin B ( p  = 0.002), shorter duration of therapy ( p  = 0.009), not combining with cefoperazone/sulbactam ( p  = 0.030), female gender ( p  = 0.004), administered for treatment of bacteremia ( p  = 0.023) and renal impairment ( p  = 0.021). Low polymyxin B doses ( p  = 0.007), not combining with cefoperazone/sulbactam ( p  = 0.024), female gender ( p  = 0.048) and renal impairment ( p  = 0.022) were also significant predictors for in-hospital mortality. Conclusions To the best of our knowledge, this is the first report on the association of inadequate dose of polymyxin B (

Predictors of polymyxin B treatment failure in Gram-negative healthcare-associated infections among critically ill patients.

Background: External ventricular drainage (EVD) has been widely used
for the purpose of cerebrospinal fluid (CSF) diversion at Hospital
Kuala Lumpur (HKL). Methods: This prospective observational study was
conducted in HKL from December 2006 to December 2008 among patients who
were subjected for EVD, following strict inclusion and exclusion
criteria. Results: The frequency of EVD-related infection was as high
as 32.2% (95% CI 23.3% to 42.57%) among 87 patients studied. This study
clearly demonstrates that tunnelling the catheter for more than 5 cm
under the scalp, from the burr hole to the exit site of the skin,
carried a significantly lower risk of infection compared with
tunnelling the catheter for 5 cm or less (OR = 0.184, 95% CI 0.083 to
0.406, P < 0.001). The majority of cases (19 out of 28) with
EVD-related infection occurred among patients catheterised for more
than 10 days (OR = 0.334, 95% CI 0.171 to 0.652, P < 0.001).
Conclusion: The technique of subgaleal tunnelling of more than 5cm and
the duration of the ventricular catheterisation of 10 days and less
should be implemented as standardised protocol at health institutions
to reduce the risk of EVD-related infections.

The risk factors of external ventricular drainage-related infection at hospital kuala lumpur: an observational study.

Acinetobacter spp. is a known nosocomial pathogen causing a wide range of clinical diseases mainly pneumonia, wound infections and blood stream infections (BSI). A cross sectional descriptive study was performed to determine the prevalence of Acinetobacter infection in Hospital Universiti Sains Malaysia, Kelantan (HUSM). The risk factors of Acinetobacter BSI were determined by 1:1 case control analytical study, involving fifty-eight confirmed cases of Acinetobacter BSI patients compared to the cases caused by Gram-negative bacteria. The prevalence of Acinetobacter BSI in the HUSM was 6.11% (95% CI 4.88-7.53%). The attack rate of Acinetobacter BSI was 2.77 episodes per 1000 hospital admissions. Acinetobacter BSI patients were mostly located in intensive care unit and had a longer intensive care unit stay. In univariate analysis, the risk factors for Acinetobacter BSI include prior exposure to antimicrobial agents such as penicillins, aminoglycosides and cephalosporins, mechanical ventilation, presence of nasogastric tube, arterial catheter and urinary catheter. In multivariate analysis, the independent risk factors for Acinetobacter BSI were prior treatment with cephalosporins (OR 3.836 95% CI 1.657-8.881 p=0.002) and mechanical ventilation (OR 3.164 95% CI 1.353-7.397 p=0.008). This study revealed that rational use of antimicrobial agents is of paramount importance to control Acinetobacter BSI.

The prevalence and risk factors of nosocomial Acinetobacter blood stream infections in tertiary teaching hospital in north-eastern Malaysia

Scalene myofascial pain syndrome is a regional pain syndrome wherein pain originates over the neck area and radiates down to the arm. This condition may present as primary or secondary to underlying cervical pathology. Although scalene myofascial pain syndrome is a well known medical entity, it is often misdiagnosed as being some other neck pain associated with radiculopathy, such as cervical disc prolapse, cervical spinal stenosis and thoracic outlet syndrome. Because scalene myofascial pain syndrome mimics cervical radiculopathy, this condition often leads to mismanagement, which can, in turn, result in persistent pain and suffering. In the worst-case scenarios, patients may be subjected to unjustifiable surgical intervention. Because the clinical findings in scalene myofascial pain syndrome are "pathognomonic", clinicians should be aware of ways to recognize this disorder and be able to differentiate it from other conditions that present with neck pain and rediculopathy. We present two cases of unilateral scalene myofascial pain syndrome that significantly impaired the patients' functioning and quality of life. This case report serves to create awareness about the existence of the syndrome and to highlight the potential morbidity due to clinical misdiagnosis.

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Mahamarowi Omar

Papers

Predictors of polymyxin B treatment failure in Gram-negative healthcare-associated infections among critically ill patients.

The risk factors of external ventricular drainage-related infection at hospital kuala lumpur: an observational study.

The prevalence and risk factors of nosocomial Acinetobacter blood stream infections in tertiary teaching hospital in north-eastern Malaysia

Scalene myofascial pain syndrome mimicking cervical disc prolapse: a report of two cases.

A case report: Community-acquired Pseudomonas aeruginosa necrotizing fasciitis in a morbidly obese diabetic young man can be fatal.