Retrospective Study of Nephrotoxicity Rate among Adult Patients Receiving Colistin Compared to ß-lactam Antibiotics.

PURPOSE: Patients receiving colistin for carbapenem-resistant gram-negative bacteria (CR-GNB) infections generally have multiple risk factors for nephrotoxicity, so it might be possible that colistin may be erroneously blamed for the nephrotoxicity. MATERIALS AND METHODS: We retrospectively analyzed case records of patients who received colistin and those who received antibiotics other than colistin [carbapenem or ß-lactam-ß-lactamases inhibitors (ßL-ßLI)] for gram-negative bacteremia. Those patients with preexisting renal failure and those who received antibiotics for <72 hours were excluded from the study. Nephrotoxicity was assessed using the risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, end-stage kidney disease (RIFLE) criteria. RESULTS: Out of the 222 patients, the colistin arm had 118 and the noncolistin arm had 104 patients. Even though the colistin arm had significantly higher number of sicker patients with neutropenia (40.7% vs 14.4%, p = 0.0001), mechanical ventilation (0.0001), having lines (0.0001), on inotropes (0.003), receiving other nephrotoxic drugs (0.0001), and higher Pitt score (p = 0.0001), there was no significant difference in the nephrotoxicity between the two arms (10.2% vs 9.6%, p = 0.89). Logistical regression showed a higher Pitt bacteremia score (p = 0.03) and a higher Charlson comorbidity index (p = 0.02), but not colistin administration (p = 0.32), were independently associated with nephrotoxicity. CONCLUSION: Administration of colistin was not associated with higher rates of nephrotoxicity than carbapenems or ßL-ßLI agents. HOW TO CITE THIS ARTICLE: Ghafur A, Bansal N, Devarajan V, Raja T, Easow J, Raja MA, et al. Retrospective Study of Nephrotoxicity Rate among Adult Patients Receiving Colistin Compared to ß-lactam Antibiotics. IJCCM 2019;23(11):518-522.

Colistin Nephrotoxicity in Adults: Single Centre Large Series from India.

CONTEXT: Limited Indian data are available on the rate of colistin nephrotoxicity and other risk factors contributing to the development of this important side effect. AIM: This study aims to generate data on colistin nephrotoxicity from a large cohort of Indian patients. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Case record analysis of patients who received colistin, in an oncology center in India, between January 2011 and December 2015. Nephrotoxicity was assessed using risk, injury, failure, loss, and end-stage (RIFLE) criteria. STATISTICAL ANALYSIS: P < 0.05 was considered as statistically significant. RESULTS: Out of the 229 patients, 13.1% (30/229) developed abnormal RIFLE. Abnormal RIFLE group (n = 30), in comparison to the normal renal function group (n = 199), had higher number of patients in intensive care unit (ICU) (96% vs. 79%, P = 0.02), higher Acute Physiology and Chronic Health Evaluation (APACHE II) score (23 vs. 19 P = 0.0001), Charlson score (5.9 vs. 4.3, P = 0.001), mechanical ventilation (90% vs. 67%, P = 0.016), 28 days mortality (63% vs. 25%, P = 0.0001), and abnormal baseline creatinine (36% vs. 8%, P = 0.001). Coadministration of vancomycin had higher rates of nephrotoxicity (P = 0.039). There was no significant difference in nephrotoxicity between 6 and 9 MU/day dosing pattern (8.8% vs. 13.8%, P = 0.058). CONCLUSION: Nephrotoxicity rate in our retrospective single center large series of patients receiving colistin was 13.1%. Patients with abnormal baseline creatinine, ICU stay, and higher disease severity are at higher risk of nephrotoxicity while on colistin. A daily dose of 9 million does not significantly increase nephrotoxicity compared to the 6 million. Concomitant administration of vancomycin with colistin increases the risk of nephrotoxicity.

Monotherapy versus Combination Therapy against Nonbacteremic Carbapenem-resistant Gram-negative Infections: A Retrospective Observational Study.

BACKGROUND: Superiority of colistin-carbapenem combination therapy (CCCT) over colistin monotherapy (CMT) against carbapenem-resistant Gram-negative bacterial (CRGNB) infections is not conclusively proven. AIM: The aim of the current study was to analyze the effectiveness of both strategies against CRGNB nonbacteremic infections. DESIGN: This was a retrospective observational cohort study. SUBJECTS AND METHODS: Case record analysis of patients who had CRGNB nonbacteremic infections identified over a period of 4 years (January 2012-December 2015) was done by medical record review at a tertiary care center in India. STATISTICAL ANALYSIS: P < 0.05 was considered as significant. Multivariate analysis was performed using Cox regression. RESULTS: Out of 153 patients (pneumonia 115, urinary tract infection 17, complicated skin and soft-tissue infection 18, intra-abdominal infection 1, and meningitis 2), 92 patients received CCCT and 61 received CMT. Univariate analysis revealed higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score, pneumonia as the diagnosis, and Klebsiella as the causative organism to be the risk factors for higher 28-day mortality (P = 0.036, 0.006, 0.016, respectively). Combination therapy had no significant impact on mortality (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.327-2.535, P = 0.857). Multivariate analysis revealed that higher APACHE II score and infection due to Klebsiella were found to be independent risk factors for higher mortality (OR = 3.16 and 4.9, 95% CI = 1.34-7.4 and 2.19-11.2, P = 0.008 and 0.0001, respectively). CONCLUSIONS: In our retrospective single-center series of CRGNB nonbacteremic infections, CCCT was not superior to CMT. Multicenter large observational studies or prospective randomized clinical trials are the need of the hour.

Monotherapy versus combination therapy against carbapenem-resistant Gram-negative bacteria: A retrospective observational study.

BACKGROUND: Colistin-based combination therapy (CCT) is extensively used to treat infections due to carbapenem-resistant Gram-negative bacteria (CRGNB). There are no data available from India on the usefulness of combination therapy, especially in the oncology setup. The aim of this study was to analyze the clinical effectiveness of CCT over monotherapy in patients with CRGNB. MATERIALS AND METHODS: We conducted a retrospective, observational study of patients with CRGNB bloodstream infections in our oncology and bone marrow transplant center. RESULTS: Over a 3-year study period (2011-2014), we could identify 91 patients satisfying study criteria. There was no statistically significant difference in the 28-day mortality between monotherapy and combination therapy arms (mono n = 26, mortality 10 (38.5%); combination n = 65, mortality 28 (40%); P = 0.886). Neutropenic patients with Enterobacteriaceae bloodstream infections performed better with combination therapy (mono n = 7, mortality 6 (85.7%); combination therapy n = 22, mortality 8 (36.4%); P = 0.035). There was no significant difference in the 28-day mortality between the two treatment arms in other subgroups. CONCLUSION: Our study did not find CCT superior to colistin monotherapy in patients with CRGNB blood stream infections; except in the subgroup of neutropenic patients with Enterobacteriaceae bloodstream infections, where combination therapy performed better.

PCR-heteroduplex analysis of TCR gamma, delta and TAL-1 deletions in T-acute lymphoblastic leukemias: implications in the detection of minimal residual disease.

Detection of MRD remains one of the major goals in the treatment of acute lymphoblastic leukemia (ALL). We have used the polymerase chain reaction (PCR)-heteroduplex (HD) analysis to assess and confirm the clonal expansion of T cell receptor (TCR) gamma and delta gene rearrangements in 24 T-ALL patients at diagnosis. 52.4% revealed Vdelta1-Jdelta1; 48% Vdelta2-Ddelta3; 62.5% Vgamma1-Jgamma1 and 46% both Vdelta1-Jdelta1 and Vgamma1-Jgamma1 clonal rearrangements. 6/24 patients had TAL-1 deletion. These clonal markers were used to monitor MRD in remission/relapse bone marrow samples for periods ranging from 6 to 75 months after diagnosis. Patients who relapsed and died revealed a continuous PCR-HD positivity in their clinical remission bone marrow samples. HD analysis established identical diagnostic clone at relapse. Patients who are in long-term clinical and morphological remission achieved PCR-HD negativity in their 8-12 months bone marrow remission samples and continue to be PCR-HD negative. MRD monitored in six patients with two diagnostic PCR--HD positive clonal markers reveal an identical pattern ensuring circumvention of false positive and negative results. Thus, we conclude that PCR followed by HD analysis is a useful technique to monitor MRD in remission/relapse samples in ALL patients.

Bone marrow involvement in a primary mediastinal extragonadal non-seminomatous germ cell tumour.

A case of primary mediastinal extragonadal germ cell tumour with involvement of bone marrow, a rare finding, is reported with a review of literature.

Persistent Müllerian Duct Syndrome (PMDS) with testicular seminoma.

Persistent Mullerian Duct Syndrome (PMDS) is characteristically associated with unilateral or bilateral cryptoorchidism. Like other undescended testis, these gonads are at an increased risk of malignant transformation. We report a case of intra abdominal seminoma in cryptorchid testis of a patient with the Persistent Mullerian Duct Syndrome, hitherto uncommonly reported in India.

Paucity of hematological neoplasia after treatment of Hodgkin disease: observation after long-term follow-up at Cancer Institute, Chennai, south India.

The purpose of the study was to evaluate the incidence of second malignancies in childhood Hodgkin disease treated with COPP and COPP/ABV (replacing mechlorethamine by cyclophosphamide) chemotherapy. In 212 children with Hodgkin disease who were under 14 years of age and treated at Cancer Institute during the 25-year period of 1970-1994, the occurrence of second malignant neoplasms was analyzed as on 31 December 1999. Eighty-two percent attained complete response. The 5- and 10-year overall survival rate was 91 and 83%, respectively. In this interm report 5 cases of second malignancies were documented. All 5 were solid tumors: one each of soft tissue sarcoma, dermatofibrosarcoma, micropapillary carcinoma of thyroid, malignant phylloides tumor of breast, and chondrosarcoma of ilium. All patients had received combination chemotherapy and radiotherapy. Interestingly, all were splenectomized. All these patients had advanced stage of cancer and were 7-14 years of age at the time of diagnosis of first primary Hodgkin disease. It is significant that there were no secondary hematological malignancies. COPP and COPP/ABV are effective therapeutic regimens. The paucity of secondary hematological malignancies is unique in this series and may be attributed to the substitution of nitrogen mustard with cyclophosphamide in the chemotherapy combination. This is an initial observation, and further follow-up is needed for a firm conclusion.