Risk Factors and Outcome of Gram-Negative Bloodstream Infection in Living-Donor Renal Transplant Recipients: A Case-Control Study From Pakistan.

OBJECTIVES: Gram-negative rods are the most common cause of bloodstream infection in renal transplant recipients. Acute rejection, urologic abnormalities, and ureteral stents are risk factors. Graft dysfunction is independently associated with gram-negative rod bloodstream infection. Our aim is to investigate the incidence, risk factors, and outcome among living donor renal transplant recipients from Pakistan. MATERIALS AND METHODS: In this case-control study, we reviewed the medical records until June 2021 of renal transplant recipients seen from 2015 to 2019 for gram negative bacteremia. For every case, controls were matched by age, date of transplant, and sex. Demographics, risk factors, graft function, and mortality were compared. Clinical features, immunosuppression, source of blood stream infection, and microbiology were noted in cases. RESULTS: Of 1677 renal transplant recipients, 44 developed gram negative bacteremia. The incidence was 5.9 per 1000 person-years. Median time since transplant was 5 months. The most common source was urinary tract infection. On univariate analysis, antithymocyte globulin, urinary tract infection, and recurrent urinary tract infections were associated with gram negative bacteremia. On multivariate analysis, urinary tract infection (adjusted odds ratio = 3.46; 95% CI, 1.27-9.37) and recurrent urinary tract infections (adjusted odds ratio = 4.03; 95% CI, 1.15-14.15) were significant risk factors. We found no difference in 30-day mortality and estimated glomerular filtration rate on last follow-up between cases and controls. Kaplan-Meier survival curves showed significant differences in graft survival in patients with gram negative bacteremia. Escherichia coli was the most common organism, with 75% ceftriaxone and 13% imipenem resistance. CONCLUSIONS: The most significant risk factor for gram negative rod bloodstream infection was recurrent urinary tract infections. Timely treatment and prevention of recurrent urinary tract infections areimperative for prevention of gram negative bacteremia.

Outcome of COVID-19 and tolerance of Remdesivir in patients with renal failure: a single center experience from Pakistan.

INTRODUCTION: Coronavirus disease-19 (COVID-19) is known to cause severe disease in chronic kidney disease and maintenance dialysis patients. We aim to report the outcome of COVID-19 and the adverse effects of Remdesivir (RDV) in patients with renal failure. METHODOLOGY: A retrospective observational study included all admitted patients with COVID-19 who received Remdesivir. Clinical characteristics and outcomes were compared in patients with renal failure (RF) and non-renal failure (NRF). We also evaluated RDV-associated nephrotoxicity and observed renal functions during antiviral treatment. RESULTS: A total of 142 patients received RDV, 38 (26.76%) in RF and 104 (73.23%) in the non-RF group. The median absolute lymphocyte count was low while C-reactive protein, ferritin, and D-dimer were significantly high on admission in the RF group. A significant number of patients in the RF group required ICU admission (58% vs. 35% p = 0.01) and expired (29% vs. 12.5 p = 0.02). Among survivors and non-survivors in the RF group, raised inflammatory markers and low platelet count on presentation were significantly associated with high mortality. Median serum creatinine (mg/dL) was 0.88 on admission, remained at 0.85 in the NRF group, and improved from 4.59 to 3.87 (mg/dL) after receiving five days of RDV in the RF group. CONCLUSIONS: COVID-19 in renal failure has a high risk for ICU admissions leading to increased mortality. Multiple comorbidities and raised inflammatory markers are predictors of poor outcomes. We observed no significant drug-related adverse effects, and none of our patients required discontinuation of RDV due to worsening renal function.

Outcome, risk factors and therapeutic strategies in carbapenem-resistant Gram-negative bacteraemia from Pakistan.

Background: Carbapenem-resistant Gram-negative (CRGN) bacteraemia has high mortality and limited therapeutic options. We assessed the risk factors and outcome of CRGN bacteraemia treated with limited options. Methods: A prospective cohort study done at a tertiary care hospital in Pakistan, from October 2021 to August 2022. All patients >18 years with CRGN bacteraemia were assessed for demographics, source, risk factors and treatment received. Outcome was assessed as bacterial clearance and all-cause mortality at Day 14 of bacteraemia. Results: We included 175 patients. Median age was 45 years (IQR 30-58) and the majority of our patients were on haemodialysis (75%). We found 14 day mortality in 26.8% of our patients; in addition, microbiological clearance was achieved in 95%. The central line (49.7%) was the most common source and Klebsiella spp. (47%) the most common organism. On multivariate analysis, risk factors for mortality were Foley's catheter [aOR 2.7 (95% CI 1.1-6.5)], mechanical ventilation [aOR 5.1 (95% CI 1.6-15.8)] and Pitt bacteraemia score >4 [aOR 3.48 (95% CI 1.1-10.5)]. Source control was a significant protective factor [aOR 0.251 (95% CI 0.09-0.6)]. The majority received a colistin-based regimen with no difference in mortality between monotherapy and combination therapy. Conclusions: Our cohort of CRGN bacteraemia is unique, comprising younger patients mostly on haemodialysis with a central line as the source of bacteraemia and we have found 14 day mortality of 27%. Colistin with various combinations can be an effective option in patients with renal failure having prompt source control.

DRUG USE RECOMMENDATIONS FOR COLISTIN INJECTION IN THE ADULT POPULATION.

BACKGROUND: Colistin, also known as Polymyxin E, was the first polymyxin antibiotic. This bactericidal antibiotic plays a vital role as salvage therapy for untreatable gram-negative. Colistin dosing regimens differ worldwide. The published guidelines have different recommendations on the dosing regimens. Further confusion exists due to two different dosing units. Currently, Pakistan has no national guidelines for colistin use. The guideline was developed to improve the safety profile by developing standardization in colistin use and thus reduce the confusion amongst clinicians. METHODS: The guideline was developed by a panel of five actively practising infectious disease specialists (physicians and pharmacists) with clinical and research expertise in this particular field. Different literature and international guidelines along with institutional data were used to develop the guideline. CONCLUSIONS: The guideline provides ten recommendations on prescribing, transcribing, posology, preparation, administration and monitoring of colistin use. The guideline will give Pakistani healthcare providers a standard approach to using rationally and effectively, and to clear confusion and questions about this medicine.

Whipple's disease in renal transplant recipients: Management experience of seven cases from Pakistan.

INTRODUCTION: Whipple's disease (WD) is a rare multi-systemic disorder caused by actinomycetes, Tropheryma whipplei. It presents with weight loss, arthralgia, and diarrhea and may involve the heart, lung, or central nervous system. The use of immunosuppressive medications or underlying immunodeficiency states are associated risk factors. Six cases in transplant recipients have so far been reported worldwide. We describe our experience of WD in renal transplant recipients. METHODS: All renal transplant recipients who presented with diarrhea and were diagnosed with WD on duodenal biopsy from 2016 till 2019 were included. Their data regarding duration since transplantation, immunosuppressive therapy, symptoms, treatment response, and outcome were analyzed. RESULTS: Seven cases were diagnosed as WD based on duodenal biopsy, with histological findings of periodic acid Schiff-positive granules in macrophages. All were males. The most common symptoms were chronic diarrhea and weight loss. Average time since transplantation was 4.8 years. All patients were on azathioprine and everolimus. Clinical relapse or adverse effects was seen in five of seven patients treated with doxycycline and hydroxychloroquine which was discontinued. Trimethoprim/sulfamethoxazole for 1 year, with initial intravenous ceftriaxone in two patients, resulted in complete remission in all patients at a follow-up period averaging 1.5 years. CONCLUSION: WDs in renal transplant recipients most commonly presents as an intestinal disorder. Treatment of 1 year with trimethoprim/sulfamethoxazole has good response with complete remission at 1.5 years of follow up.

A case series of multidrug-resistant tuberculosis in renal transplant recipients: Challenges in management from a TB endemic country.

Multidrug-resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis that is resistant to isoniazid and rifampicin (Rif). The use of immunosuppressive drugs in solid organ transplant recipients can increase the risk of TB. Management of MDR-TB is quite challenging in the general population with poor compliance owing to lengthy treatment duration and drug toxicities. New drugs as well as shorter regimen have been used to increase the likelihood of adherence. The experience of treating MDR-TB in the transplant recipients is limited. New drugs like bedaquiline, linezolid, clofazimine, and delamanid have rarely been used in transplant recipients. To the best of our knowledge, only 14 cases of MDR-TB in transplant population have been reported in the literature and no case from Pakistan, a high TB burden country. We are reporting our experience of treating 4 renal transplant recipients. We used new drug regimen and found many side effects. Treatment outcome was successful with complete cure in 3 of our patients, however one died of severe drug toxicity. The most worrisome drug interaction was between azathioprine and linezolid, with life-threatening thrombocytopenia. There was no graft dysfunction noted at the end of the therapy. The management of MDR-TB in transplant recipients is challenging; excellent coordination between transplant team and Infectious Diseases Physician for close monitoring and follow-up is needed.

Treatment outcome and adverse effects of colistin in adult patients with carbapenem-resistant gram-negative bacteremia from Pakistan.

BACKGROUND: Polymyxins (colistin) have emerged for the treatment of carbapenem resistant (CR) gram-negative infections. There is a paucity of data on treatment outcomes and adverse effects of high-dose colistin treatment in Pakistan. The aim of this study was to determine the efficacy and toxicity of colistin in CR bacteremia, including patients with renal failure and on hemodialysis, and to determine patient outcomes. METHODS: This prospective cohort study was performed from May to December 2017 at Sindh Institute of Urology and Transplantation, Karachi, Pakistan. Patients aged >18 years with documented gram-negative bacteremia were included. Data were compared between those who received colistin and those who did not, including risk factors for CR bacteremia, bacterial clearance, adverse effects, and all-cause mortality up to 14 days of follow-up. RESULTS: The study included 137 patients, 73 (53.3%) in the colistin group and 64 (46.7%) in the non-colistin group. Patients in the colistin group were 1.47 times more likely to have died by day 14 of follow-up as compared to those in the non-colistin group (19.2% vs 7.8%; relative risk 1.47, p= 0.05). Patients in both groups achieved more than 80% bacteriological clearance. The colistin group patients were less likely to have received appropriate empirical antibiotics as compared to the non-colistin group patients (4.1% vs 62.5%; relative risk 0.09, p< 0.001). Factors significantly associated with mortality were inappropriate empirical antibiotics and acute renal failure. Of the 73 patients in the colistin group, 27 (37.0%) developed reversible neurological adverse effects. Patients with renal insufficiency, not on hemodialysis, were evaluated for colistin nephrotoxicity. Creatinine decreased from 8.08 mg/dl at baseline to 4.85 mg/dl on day 7 in the colistin group, and from 6.5 mg/dl to 3.9 mg/dl in the non-colistin group. Patients with normal renal function had no significant rise in serum creatinine. CONCLUSIONS: Colistin is efficacious in clearing bacteremia even in patients with impaired renal function. The adverse effects were found to be minimal and reversible. We recommend the use of colistin in combination with carbapenems for CR gram-negative bacteria in renal failure. Most importantly, however, this study highlights the role of empirical colistin treatment in patients with risk factors for CR bacteremia.