High-risk clones and novel sequence type ST4497 of Klebsiella pneumoniae clinical isolates producing different alleles of NDM-type and other carbapenemases from a single tertiary-care centre in Egypt.

Enterobacteria producing NDM carbapenemases represent a severe diagnostic and therapeutic challenge in healthcare settings. Infections caused by NDM-positive strains are usually associated with high mortality rates and very limited treatment options. A total number of 33 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates were included in this study, comprising 30 recovered from clinical diagnostic samples and 3 cultured from screening rectal swabs taken at patient admission. Bacterial identification was performed by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS) and antibiotic susceptibility testing was performed by reference broth microdilution and a commercial automated method. Isolates were investigated for carbapenemase production using the ß-CARBA test, the modified carbapenem inactivation method (mCIM) and, for the 30 clinical isolates, by MALDI-TOF/MS, using the MBT STARⓇ-Carba IVD Kit. Carbapenem resistance genes were characterised by PCR and sequencing. Seven different blaNDM gene variants were identified in 94% of the isolates, whilst three variants of blaOXA-48-like were detected in 27% of the isolates. Most CRKP corresponded to high-risk clones (ST147, ST11 and ST15). Novel ST4497 is reported for the first time in this study as well as the first emergence of K. pneumoniae ST231 producing OXA-232 in Egypt. These results indicate an ongoing evolution of the blaNDM genes in our area and confirm the need for a maintained surveillance system in order to monitor the spread of these mobile blaNDM genes.

Comparison of high and low dose of cyclophosphamide in lupus nephritis patients: a long-term randomized controlled trial.

To evaluate the outcome of low doses of cyclophosphamide (Cyclo) therapy in lupus nephritis (LN) patients, we studied 117 biopsy-proven, de novo LN WHO class IV patients double-blinded and randomized in December 1997 to receive Cyclo in different doses; Group I (n=73) received Cyclo 10 mg/kg monthly for six months then every two months for 12 months. Group II (n=44) received Cyclo 5 mg/kg monthly for six months then every two months for 36 months. The patients were followed-up till January 2007. Six months post-induction values for creatinine clearance were significantly higher in Group I (67.7 ± 28.6 mL/min) compared with Group II (55.1 ± 30.1 mL/min), P = 0.026. Serum C4 and ANA were not significantly different between the groups (P > 0.05). At the mean follow-up of 6.77 ± 3.3 years, the mean creatinine clearance was 44.74 ± 31.7 mL/min in Group I vs. 49.3 ± 38.8 in Group II. Urinary protein was 1.65 ± 1.8 g/dL in Group I vs. 1.02 ± 1.01 in Group II (P = 0.03). The survival curve showed that kidney survival overtime was comparable in both groups (P = 0.2). Complete remission was observed in 25 (34.2%) patients in Group I vs. 11 (25%) in Group II (P = 0.288), while partial remission was similar in both groups; 43 (58.9%) patients in Group I vs. 26 (59%) patients in Group II. End-stage renal disease was observed in 10 (13.7%) patients in Group I vs. 9 (20.4%) patients in Group II (P = 0.359). Side-effects were more frequent in Group I patients than in Group II patients; gonadal toxicity and malignancy were lower in Group II patients (P = 0.0000). Moreover, different infections occurred in 23 (31.3%) patients vs. six (13.6%), digital infarcts occurred in 1.35% vs. 0%, diabetes in 4.1% vs. 2.27%, and vasculitis in 4.1% vs. 2.27% in Group I vs. Group II, respectively. Sustained amenorrhea without pregnancy was observed in both groups; however, significantly more in Group I patients, P ≤ 0.05. We conclude that low-dose Cyclo therapy is sufficiently effective for WHO class IV LN patients with lower side-effects compared with standard dose.