Evaluation of bacteriophage cocktail on septicaemia caused by colistin-resistant Acinetobacter baumannii in immunocompromised mice model.

Background & objectives: Since the bacterium, Acinetobacter baumannii (AB) has acquired resistance to almost all commercially available antibiotics, the search for alternative treatment options continues to be need of the hour. Bacteriophage therapy seems to be the most promising amongst various proposed alternatives (e.g. antimicrobial peptides, bacteriocin, probiotics, etc.). The present study, therefore, aimed to evaluate the effect of different dosages of specific phages in immunocompromised rodents in a septicaemia model caused by AB mimicking real clinical situations. Methods: The three most active and unique phages (ɸAb4, ɸAb7 and ɸAb14) were selected for this study. A constant dose (100 µl of 108 pfu/ml) of AB was given in all the experiments. Five different sets of experiments were designed: prophylactic administration of phage cocktail in the volume of 100 µl (109 pfu/ml) before and simultaneous with the bacterial challenge; and therapeutic i.e. administration of phage cocktail six, 12 and 24 h after bacterial challenge. Since there were deaths in mice when phage was given 24 h after bacterial challenge, the reduced dosage i.e. 100 µl of 107, 10[6], 105 pfu/ml of phage cocktail was also evaluated. Results: The administration of 100 µl (109 pfu/ml) of phage cocktail after six, 12 and 24 h of the bacterial challenge resulted in the mortality ranging between 20 to 60 per cent. However, no mortality could be observed with simultaneous or prophylactic administration of phages with the bacterial challenge. No mortality was observed with reduced doses of the cocktail (10[6] and10[5] pfu/ml). Interpretation & conclusions: As per the results of this study, it may be concluded that even if patients with acute infections report late to the hospital, a relatively low dose of the phage cocktail may be therapeutically beneficial.

Drug Resistance Pattern in the Recent Isolates of Salmonella Typhi with Special Reference to Cephalosporins and Azithromycin in the Gangetic Plain.

INTRODUCTION: Typhoid fever is an endemic disease in India against which many antibiotics are available. In the recent times, emerging resistance to traditional antibiotics, such as Ampicillin, Chloramphenicol and Trimethoprim/sulfamethoxazole, Azithro-mycin and third generation Cephalosporins are being reported and increasingly being used in the treatment of invasive Salmonella infections. However, the latter two drugs have been reported with occasional clinical failures. Currently, we do not have data regarding their drug resistance levels in the recent isolates of Salmonella enterica subspecies enterica serotype Typhi. AIM: To determine the current levels of drug resistance of the two drugs (i.e., cephalosporins and azithromycin) against S. Typhi isolates. MATERIALS AND METHODS: It is a prospective case study. A total of 47 recent strains of S. Typhi were isolated from blood and stool specimens. These isolates were subjected to identification and confirmation by biochemical, serological tests followed by genotypic methods. The antimicrobial testing was done by disc diffusion and Minimum Inhibitory Concentration (MIC) methods for various in use antibiotics including ceftriaxone and azithromycin from February 2011 to March 2013 in the Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. RESULTS: It was intriguing to see the return of conventional drugs such as chloramphenicol, amoxicillin and co-trimoxazole. The drugs like quinolones, ceftriaxone and azithromycin were found to be ineffective against >20% of the isolates. However, nalidixic acid was found to have maximum resistance (36/47,76.6%) while highest sensitivity was observed for chloramphenicol (1/47,2.1%). Moreover, co-trimoxazole (9/47,19.1%) has displayed with significant come back. CONCLUSION: It could be concluded that combination of amoxicillin and co-trimoxazole would prove as good as azithromycin or ceftriaxone alone for empirical therapy of S. Typhi infection. However, detection of an isolate (1/47, 2.1%), sensitive only to chloramphenicol, a drug known for causing bone marrow suppression, is an alarming sign.