Iron regulated outer membrane proteins (IROMPs) as potential targets against carbapenem-resistant Acinetobacter spp. isolated from a Medical Centre in Malaysia.

Background & objectives: Carbapenem-resistant Acinetobacter spp. have gained increasing significance as opportunistic pathogens in hospitalized patients. Carbapenem resistance is often associated with the loss and/or decrease in outer membrane proteins (OMP) and overexpression of multidrug efflux systems. However, carbapenem-hydrolysing β-lactamases of Ambler Class B (metallo-enzymes) and Ambler Class D (oxacillinases) have also been detected in Acinetobacter spp. In this study we have investigated the role of the iron regulated outer membrane protein (IROMPs) and the loss of a 29-kDa OMP in carbapenem resistance of Acinetobacter calcoaceticus. Methods: Carbapenem resistant clinical isolates (n=39) of Acinetobacter baumannii / calcoaceticus were used. Identification of Acinetobacter spp. at species level was done by amplified ribosomal DNA restriction analysis (ARDRA). MIC was evaluated using agar dilution method according to CLSI standards. Presence of outer membrane proteins were determined by SDS-PAGE. A representative strain of A. calcoaceticus, S26 with the loss of 29-kDa OMP was selected for further analysis as strain S26 had unique resistance mechanism, that is, the presence of IMP-4 metallo-β-lactamases. IROMPs were expressed under iron deficit conditions. Bands corresponding to IROMPs were excised from SDS-PAGE and used to immunize rabbits for the production of polyclonal antibodies. The antibodies raised against IROMPs were detected by an in-house ELISA and then used for bactericidal activity against carbapenem resistant A. baumannii / calcoaceticus. Results: All isolates were resistant to all antibiotics including imipenem and meropenem and had loss of a 29-kDa OMP. The polyclonal antibodies showed bactericidal effect against the organism tested and it specifically killed the bacteria grown in iron deficit medium. Interpretation & conclusions: In this study, a 29-kDa OMP has been identified to be the major outer membrane protein in A. baumannii / calcoaceticus and loss of this porin and overexpression of IROMPs have contributed to carbapenem resistance. Polyclonal antibodies raised against IROMPs may have a role in antimicrobial therapy in these isolates.

Plasma CRP level predicts left ventricular function and exercise capacity in patients with acute myocardial infarction.

BACKGROUND: C-reactive protein estimation can help in predicting short- and long-term prognosis after acute myocardial infarction. High plasma C-reactive protein level in the acute phase strongly indicates a poor clinical outcome of the patients with myocardial infarction. METHODS AND RESULTS: One hundred consecutive patients admitted with ST elevation myocardial infarction in the intensive coronary care unit in our hospital who were able to do symptom-limited treadmill test during early recovery phase were studied. Plasma C-reactive protein was measured at the time of admission by immunoturbidity method. The normal value of the C-reactive protein was taken as 0.8 mg/dl. Echocardiographic study was done on day three of admission and ejection fraction was estimated by modified Simpson's method. Symptom-limited treadmill exercise test was done in all the patients. Patients were classified into two groups based on level of C-reactive protein: those with low C-reactive protein level (1.26 +/- 0.91 mg/dl, n=40) and those with high C-reactive protein level (6.52 +/- 3.97 mg/dl, n=60). Ejection fraction was lower in high C-reactive protein group (46.7 +/- 11.9%) compared to low C-reactive protein group (56.9 +/- 7.7%) (p = 0.011). Exercise capacity was lower in high C-reactive protein group (2.8 +/- 1.4 METs) compared to low C-reactive protein group (5.5 +/- 2.5 METs) p = 0.027). CONCLUSIONS: C-reactive protein levels are an index of the severity of myocardial necrosis which translate to worse left ventricular function. Higher the C-reactive protein level, lower the ejection fraction and worse may be the prognosis.