The Effect of Double Carbapenem Regimen in the Management of Carbapenem-Resistant Klebsiella pneumoniae Infections: A Report of Five Cases.

The treatment of infections caused by carbapenem-resistant organisms is challenging. Carbapenems in combination with vaborbactam and relebactam are recommended to treat infections caused by extensively drug-resistant organisms including carbapenemase-producing isolates, while ceftazidime-avibactam plus aztreonam, or cefiderocol is recommended for infections caused by New Delhi metallo beta-lactamase (NDM)-producing Enterobacteriaceae. As, in India, except for ceftazidime-avibactam and aztreonam, the other drugs are not approved for marketing, in this case report, the role of a double carbapenem regimen (ertapenem plus meropenem) in the treatment of carbapenem-resistant Klebsiella pneumoniae infections has been presented. In one case, the in vitro effect of the double carbapenem regimen on pan drug-resistant (PDR) K. pneumoniae isolates from a blood culture specimen of a critically ill patient using a time-kill study is presented. In this case, only a double carbapenem regimen with 2 MIC (minimum inhibitory concentration) meropenem + 2 MIC ertapenem demonstrated bactericidal activity by inhibition of bacterial growth of PDR K. pneumoniae isolate, at four and eight hours, which was sustained till 24 hours. However, while 2 MIC meropenem + 2 MIC colistin inhibited bacterial growth at four hours and eight hours, bacterial regrowth occurred by 24 hours. In addition, four cases of critically ill patients with infections caused by carbapenem-resistant Enterobacteriaceae are presented in whom a double carbapenem regimen was recommended for treatment. Of these four cases, a complete clinical cure was observed in three cases, and a microbiological cure in the fourth case. As the double carbapenem regimen demonstrated effect in an in vitro time-kill study in the first case and on clinical outcomes in three out of the latter four cases, it appears to be a life-saving, salvage therapy in infections caused by carbapenem-resistant K. pneumoniae in India.

Evaluation of Risk Factors for Development of Anti-Tubercular Therapy Induced Hepatotoxicity: A Prospective Study.

BACKGROUND: Incidence of Antitubercular Therapy (ATT)-induced hepatotoxicity is higher in India when compared to Western countries. As the occurrence of ATT-induced hepatotoxicity is unpredictable, serial intensive monitoring of hepatic function is now being recommended by the American Thoracic Society in individuals at high risk. This study was done to evaluate the risk factors for the development of ATT induced hepatotoxicity in India. METHODOLOGY: In this prospective, observational study, patient characteristics of microbiologically/ radiologically/ histopathologically confirmed tuberculosis were prospectively compiled. Serial liver function tests were done once a month in all patients. Patients who developed ATT-induced hepatotoxicity were considered as the study group and those who did not develop the event as a control group. The primary outcome measure was to estimate the hazard ratios associated with risk factors for the development of ATT induced hepatotoxicity. Cox Regression Analysis was done using SPSS 20. RESULTS: A total of 200 patients were enrolled in the study, of them, 14% developed ATT-induced hepatotoxicity and 86% did not develop the event. The baseline liver function tests in the study group and control group were within normal limits. Female gender, alcoholism, HIV co-infection and age >35 yrs were identified to have a higher risk for development of ATT-induced hepatotoxicity, while cases with pulmonary tuberculosis were found to be at lower risk of developing event. CONCLUSION: Intensive liver function monitoring needs to be done in patients with these risk factors, female gender, alcoholism, HIV co-infection, extra-pulmonary tuberculosis and age >35 yrs.

Ganciclovir-tenofovir interaction leading to tenofovir-induced nephrotoxicity.

Viral enteritis is an important gastrointestinal disorder in human immunodeficiency virus (HIV)-infected patients. Cytomegalovirus (CMV) is the most common opportunistic agent in these patients. As ganciclovir and tenofovir are the most commonly used drugs for the treatment of CMV and HIV infection, respectively, this case report showcases the potentiality of drug interaction as well as the safety measures to be taken when using these two drugs together in unavoidable situations.

A randomized, double blind, placebo controlled, cross over study to evaluate the analgesic activity of Boswellia serrata in healthy volunteers using mechanical pain model.

OBJECTIVE: Experimental pain models in human healthy volunteers are advantageous for early evaluation of analgesics. All efforts to develop nonsteroidal anti-inflammatory drugs (NSAIDs) which are devoid of gastrointestinal and cardiovascular system effects are still far from achieving a breakthrough. Hence we evaluated the analgesic activity of an ayurvedic drug, Boswellia serrata by using validated human pain models which has shown its analgesic activity both in-vitro and preclinical studies to evaluate the analgesic activity of single oral dose (125 mg, 2 capsules) of Boswellia serrata compared to placebo using mechanical pain model in healthy human subjects. MATERIALS AND METHODS: After taking written informed consent, twelve healthy subjects were randomized (1:1) to receive single oral dose of Boswellia serrata (Shallaki (®)) 125 mg, 2 capsules or identical placebo in a crossover design. Mechanical pain was assessed using Ugo basile analgesymeter (by Randall Selitto test) at baseline and at 1 hr, 2 hrs and 3 hrs after test drug administration. Pain Threshold force and time and Pain Tolerance force and time were evaluated. Statistical analysis was done by paired t-test. RESULTS: Twelve healthy volunteers have completed the study. Mean percentage change from baseline in Pain Threshold force and time with Boswellia serrata when compared to placebo had significantly increased [Force: 9.7 ± 11.0 vs 2.9 ± 3.4 (P = 0.05) and time: 9.7 ± 10.7 vs 2.8 ± 3.4 (P = 0.04)] at third hr. Mean Percentage change from baseline in Pain Tolerance force and time with Boswellia serrata when compared to placebo had significantly (P ≤ 0.01) increased at 1 hr, 2 hrs and 3 hrs. CONCLUSION: In the present study, Boswellia serrata significantly increased the Pain Threshold and Pain Tolerance force and time compared to placebo. Both study medications were well tolerated. Further multiple dose studies may be needed to establish the analgesic efficacy of the drug.

Effect of beta-1-blocker, nebivolol, on central aortic pressure and arterial stiffness in patients with essential hypertension.

INTRODUCTION: Blood pressure (BP) reduction is the major determinant of benefit provided by antihypertensive treatment. Although different drugs reduce peripheral BP to some extent, there may be a significant difference in their effect on central BP reduction. It has been shown that beta-blockers are efficient in reducing peripheral, but not central BP. This study was done to assess the effect of beta-1-blocker, nebivolol, in patients with essential hypertension on central aortic pressures and arterial stiffness. MATERIALS AND METHODS: In this single arm, open-labeled study, 13 patients were given nebivolol, 5 mg orally once daily for 15 days. Primary outcome was change in central aortic pressure, and other measures of efficacy included changes in brachial BP, augmentation index (AIx%), AIx%@75 HR, augmentation pressure (AP), heart rate (HR), and carotid femoral pulse wave velocity (PWVcf). RESULTS: Nebivolol 5 mg significantly reduced central aortic pressures [systolic BP, 131.5-111.6 mmHg; diastolic BP, 96.3-81.7 mmHg; Mean Arterial Pressure (MAP), 111.3-94.0 mmHg (all P<0.0001), and Pulse Pressure (PP), 35.2-29.7 mmHg (P<0.01)]. AIx%@75 HR reduced from 29 to 21.6 (P<0.001) and PWVcf reduced from 8.6 to 7.2 m/s (P<0.001). One subject was lost to followup. CONCLUSION: Nebivolol 5 mg demonstrated antihypertensive efficacy in patients with essential hypertension by reducing not only peripheral brachial pressures, but also significantly reducing central aortic pressures, augmentation index, and carotid femoral pulse wave velocity, which is the marker of arterial stiffness.