Novel VIM Metallo-β-Lactamase Variant from Clinical Isolates of Enterobacteriaceae from Algeria

Five different strains of bacteria belonging to the family Enterobacteriaceae were isolated from two patients hospitalized in the intensive care unit of the Central Military Hospital of Algiers, Algeria. All five strains, one Providencia stuartii strain, two Escherichia coli strains, and two Klebsiella pneumoniae strains, were intermediate or resistant to all β-lactams, including carbapenems. Synergy between imipenem and EDTA was observed for all five strains. The results of the PCR experiment confirmed the presence of a bla_VIM gene in all five strains. The bla_VIM genes were located as part of a class 1 integron on a 180-kb conjugative plasmid. They encoded a novel metallo-β-lactamase designated VIM-19, which differed from the parental enzyme VIM-1 by only two substitutions: Ser228Arg, previously observed in the closely related enzyme VIM-4, and Asn215Lys, not previously observed in other VIM-type carbapenemases. VIM-19 was further characterized after purification through determination of its kinetic constants. This enzyme was inhibited by EDTA and hydrolyzed penicillins, cephalosporins, and carbapenems, as observed for other VIM-type carbapenemases but with greater catalytic efficiency against penicillins than VIM-1. VIM-19 is the first carbapenemase enzyme identified from an isolate from Algeria. These results confirm the emergence of VIM-4-like enzymes in members of the family Enterobacteriaceae from Mediterranean countries.Carbapenems are the most active molecule in β-lactams with 98% susceptibility worldwide among bacteria belonging to the family Enterobacteriaceae (24). However, a growing number of carbapenemase-producing strains have been identified since the beginning of the 1990s. They displayed variable in vitro levels of resistance to carbapenems, including susceptibility (24), but were clinically resistant to these molecules (35). The possible low level of resistance makes reliable detection of such strains difficult (35).The geographical distribution of these strains differs: those producing class A KPC-type carbapenemases have been more frequently observed in the United States and in Israel, whereas those producing VIM- and IMP-type class B β-lactamases were generally encountered in Asia and in the northern part of the Mediterranean basin (24). Among these enzymes, metallocarbapenemases are especially worrying because they virtually hydrolyze all classes of β-lactams, except aztreonam (35). Initially observed in Pseudomonas aeruginosa and Acinetobacter spp., they spread to members of the family Enterobacteriaceae during the late 1990s and the 2000s (24). The most frequently acquired metallo-β-lactamases (MBLs) are the IMP and VIM types (24). Four other types of acquired MBLs in P. aeruginosa isolates from Brazil (SPM-1) (34) and Germany (GIM-1) (5), in Acinetobacter baumannii isolates from Korea (SIM-1) (17), and in a Citrobacter freundii isolate from Japan (KHM-1) (30) have recently been described.VIM-producing members of the family Enterobacteriaceae have been involved in different outbreaks in particular in Italy and Greece during the 2000s (4, 23, 33). The southern part of the Mediterranean basin seemed to be spared by such strains until 2006, when VIM-4-producing strains of Klebsiella pneumoniae were identified during a nosocomial outbreak in a Tunisian hospital (14), suggesting a possible dissemination in northwestern Africa.Between January and May 2008, five imipenem-resistant strains belonging to bacteria in the family Enterobacteriaceae were recovered from two patients in the intensive care unit of the Central Military Hospital of Algiers, Algeria. We identified a novel metallocarbapenemase, VIM-19, in these strains. This is the first report of VIM-producing strains in Algeria.     

Where to from here?

Although this conceptual framework is easy to understand, the data requirements for the mathematical model that underpins the framework are complex and must be defined carefully. In our framework, simulations of the health system are used to provide needs-based estimates that are aimed at optimizing outcomes. This type of model builds on research conducted at the macro, meso, and micro levels in order to reflect the complexity of relationships in the health human resource process. The papers in this issue of the Journal provide insight into specific constructs of the model. At the macro level, Tomblin Murphy explores methodological challenges in HHRP research. She examines common assumptions and the validity of their use in modelling in all aspects of the proposed framework. Tourangeau and colleagues report on the impact of hospital nurse-staffing decisions on 30-day mortality rates. Their model adds to our knowledge of the relationships among the management, deployment, and utilization of nursing services and patient/population outcomes. Shamian and colleagues explore the relationship between hospital-level indicators of the work environment and aggregated indicators of health and well-being for registered nurses employed in acute-care hospitals in the province of Ontario. This paper contributes to our understanding of how management decisions regarding the work environment influence nurse outcomes. Manojlovich and Ketafian explore the conflict between the practice of nursing and the organizational structure of many hospitals. This study provides insight into the management aspects of how the work unit is organized and the process of care delivery. Zboril-Benson examines the reasons for nurse absenteeism in the province of Saskatchewan. Birch describes the need for the planning process to take into account demographic changes in both populations and provider groups. A major challenge in modelling health human resources is access to meaningful databases for planning purposes. Pringle describes a unique Ontario initiative currently underway to develop and validate a nurse-sensitive set of data that will be routinely collected and will enhance HHRP in that province. Since the science that underpins HHRP is complex and rapidly changing, few books have been written on the subject. Reflecting the dynamic nature of the science, Tomblin Murphy and Barrath provide an excellent review of "grey literature" and useful Web sites for those interested in HHRP.     

Silver Nanoparticles from Cow’s Milk to Combat Multidrug-Resistant Gram-Negative Bacteria from Clinical Isolates

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The emergence of multidrug-resistant (MDR) bacteria is causing severe and lethal human infections and is...     

Does spasticity result from hyperactive stretch reflexes? Preliminary findings from a stretch reflex characterization study

Purpose:?To characterize the stretch reflex response of the biceps brachii in stroke patients with elbow spasticity (prior to or within 15?min of treatment with botulinum toxin) and non-impaired volunteers with the aim of quantifying the stretch reflex excitability and observe the differences between the groups.

Methods:?A cross-sectional study. Stretch reflexes from the biceps brachii were elicited following a controlled elbow extension. The amplitude, latency, rise time and duration, calculated from surface EMG recordings from the biceps brachii, were used to characterize the stretch reflex response.

Results:?Seventeen non-impaired and 14 stroke patients participated. The amplitude was significantly lower in stroke patients than in non-impaired volunteers (p?<?0.05). The latency was significantly shorter in stroke patients than in non-impaired volunteers (p?<?0.05). There were no significant differences in rise time or duration (p?>?0.10).

Discussion:?Reduction in the amplitude in stroke patients was unexpected suggesting the stretch reflex is not necessarily hyper-excitable in people with clinically diagnosed spasticity. Latency differences suggest decreased presynaptic inhibition and/or increased motor neurone excitability can occur following a stroke. However, carry over effects from previous botulinum toxin treatment may have confounded amplitude measurements. Further work evaluating the excitability of the stretch reflex independent of Botulinum toxin and its contribution to resistance to passive stretching is being conducted.     

Does spasticity result from hyperactive stretch reflexes? Preliminary findings from a stretch reflex characterization study

PURPOSE: To characterize the stretch reflex response of the biceps brachii in stroke patients with elbow spasticity (prior to or within 15 min of treatment with botulinum toxin) and non-impaired volunteers with the aim of quantifying the stretch reflex excitability and observe the differences between the groups. METHODS: A cross-sectional study. Stretch reflexes from the biceps brachii were elicited following a controlled elbow extension. The amplitude, latency, rise time and duration, calculated from surface EMG recordings from the biceps brachii, were used to characterize the stretch reflex response. RESULTS: Seventeen non-impaired and 14 stroke patients participated. The amplitude was significantly lower in stroke patients than in non-impaired volunteers (p<0.05). The latency was significantly shorter in stroke patients than in non-impaired volunteers (p<0.05). There were no significant differences in rise time or duration (p>0.10). DISCUSSION: Reduction in the amplitude in stroke patients was unexpected suggesting the stretch reflex is not necessarily hyper-excitable in people with clinically diagnosed spasticity. Latency differences suggest decreased presynaptic inhibition and/or increased motor neurone excitability can occur following a stroke. However, carry over effects from previous botulinum toxin treatment may have confounded amplitude measurements. Further work evaluating the excitability of the stretch reflex independent of Botulinum toxin and its contribution to resistance to passive stretching is being conducted.