Newer ?-Lactam/?-Lactamase inhibitor for multidrug-resistant gram-negative infections: Challenges, implications and surveillance strategy for India

Antimicrobial resistance (AMR) is a major public health concern across the globe, and it is increasing at an alarming rate. Multiple classes of antimicrobials have been used for the treatment of infectious diseases. Rise in the AMR limits its use and hence the prerequisite for the newer agents to combat drug resistance. Among the infections caused by Gram-negative organisms, beta-lactams are one of the most commonly used agents. However, the presence of diverse beta-lactamases hinders its use for therapy. To overcome these enzymes, beta-lactamase inhibitors are being discovered. The aim of this document is to address the burden of AMR in India and interventions to fight against this battle. This document addresses and summarises the following: The current scenario of AMR in India (antimicrobial susceptibility, resistance mechanisms and molecular epidemiology of common pathogens); contentious issues in the use of beta-lactam/beta-lactamase inhibitor as an carbapenem sparing agent; role of newer beta-lactam/beta-lactamase inhibitor agents with its appropriateness to Indian scenario and; the Indian Council of Medical Research interventions to combat drug resistance in terms of surveillance and infection control as a national response to AMR. This document evidences the need for improved national surveillance system and country-specific newer agents to fight against the AMR.

Standardization of fungal polymerase chain reaction for the early diagnosis of invasive fungal infection.

Background: An early initiation of antifungal therapy in invasive fungal infections (IFIs) is critical in reducing the high mortality rate. Current diagnosis of fungal infection relies on microscopy, culture, antigen, antibody specific tests and histological diagnosis. However, these tests either lack sensitivity or specificity. There is thus the need for a rapid, specific and accurate diagnostic method. Objective: The aim of our study was to establish PCR for the rapid detection of Candida and Aspergillus species in clinical specimens with improved sensitivity and specificity. Materials and Methods: A total of 71 proven cases of IFI (confirmed by culture) were collected. A total of 15 healthy, 15 patients suffering from bacterial sepsis and 15 patients with HIV, HBV viral infections were included as controls. Clinical specimens were subjected to a standardized nested amplification to produce Round I (504 bp) and Round II (150 bp) amplicons. Restriction digestion was performed on these products for further identification. Results: Analytical sensitivity was determined using 10 6 -10 CFU/ml of cell suspension. The lower detection limit of the assay was 10 CFU/ml of blood. This test was 100% sensitive and specific with a positive predictive value of 100% and a negative predictive value of 96.7%. Conclusion: The assay was found to be effective for the rapid detection of Candida and Aspergillus in clinical specimens.

Acute enteritis associated with pneumococcal bacteremia.

We describe an elderly male who had a two day history of fever, abdominal pain and watery loose motions. Clinical examination was positive for abdominal right lower quadrant tenderness and moderate dehydration. Stool examination revealed inflammatory diarrhea. Considering the high prevalence of extended spectrum β-lactamases (ESBL) producing Gram-negative infections, he was treated with Piperacillin/Tazobactam. Surprisingly, his blood culture which was taken on admission returned positive for Streptococcus pneumoniae after two days, which was coincident with resolution of fever and diarrhea. This patient had no other clinically apparent source of Pneumococcal infection and we believe that he had Pneumococcal enteritis with bacteremia. There are very few reported cases of isolated Pneumococcal enteritis in the literature. Therefore, we report this unusual form of Streptococcus pneumoniae infection both because of its rarity and its potentially life-threatening but still curable nature. ©

Enteric fever in Mumbai--clinical profile, sensitivity patterns and response to antimicrobials.

AIMS: Enteric fever is endemic in Mumbai and its diagnosis poses several problems. Our main aim was to study the clinical profile, haematological features of culture proven typhoid cases, the antimicrobial susceptibility pattern of the isolates and the time to defervescence with the treatment received. MATERIAL AND METHODS: This was a retospective chart review of all cases of culture proven enteric fever carried out at a tertiary care private hospital in Mumbai over the period January 2003 to September 2005. RESULTS: Culture positivity in our study was 52.6%. Sixty one percent of the isolates were Salmonella typhi while 39% were Salmonella paratyphi A. An absolute eosinopenia was seen in 76.9% of the patients. Before being admitted to the hospital, 46.2% received antibiotics. The mean time to defervescence in patients who received prior antibiotics was 4.5 days while that in those who did not receive prior antibiotics was 5.1 days. CONCLUSIONS: A high culture positivity despite prior or ongoing antibiotic treatment was seen. Absolute eosinophil count of 0% could be an important marker of typhoid. High prevalence of nalidixic acid resistance, a marker of resistance to fluoroquinolones was observed. Combination treatment was not found to be superior to treatment with a single antibiotic.

Purpura fulminans due to Enterococcus faecalis.

We report a case of a 73 year old man who developed purpura fulminans due to Enterococcus faecalis sepsis. The patient was treated successfully with oral linezolid. Early diagnosis of the microbial etiology of purpura fulminans is important. If Enterococcus faecalis is found as the causal organism, appropriate antimicrobial therapy may be used.

Spontaneously developing autoantibody to factor VIII in an elderly woman: diagnostic and therapeutic challenges.

An elderly woman with a continuously bleeding small wound was investigated for the presence of antibodies to FVIII using activated partial time-based screening and confirmatory tests. A late acting coagulation factor inhibitor was detected. The same was characterised to be a low titre antibody against FVIII (5.2 Bethesda units). Cryoprecipitate infusions, corticosteroids and topical desmopressin were unsuccessful in controlling the bleeding. Addition of cyclophosphamide brought about stoppage of bleeding and disappearance of the autoantibody.

Kikuchi Fujimoto disease with unusual features.

An uncommon case of Kikuchi Fujimoto disease with unusual associated serologic-autoimmune abnormalities and aseptic meningitis is reported for its rarity.

Jugular venous thrombosis in HIV-seropositive man.

We report a patient with left jugular vein thrombosis, who was found to be HIV +ve, with increased homocysteine, decreased vitamin B12 and increased fibrinogen levels. Other markers for thrombophilia were absent. Whether HIV infection may be causally associated with venous thrombosis is discussed.

Venereal transmission of Japanese encephalitis virus in Culex bitaeniorhynchus mosquitoes.

Experiments were conducted in the laboratory on C. bitaeniorhynchus to determine the possible role of males in maintaining or sustaining the Japanese encephalitis virus activity in nature. It was found that infected males are capable of passing on the virus to female mosquitoes while mating. The occurrence of phenomenon of venereal transmission of this virus may have epidemiological importance.

First isolation of Japanese encephalitis virus from the mosquito, Culex tritaeniorhynchus Giles, 1901 (Diptera: Culicidae) in Gorakhpur district, Uttar Pradesh.

A strain of Japanese encephalitis (JE) virus has been isolated from a pool of female mosquitoes of C. tritaeniorhynchus, using C. bitaeniorhynchus cell line. This is the first report of JE virus isolation from mosquitoes in Gorakhpur district of Uttar Pradesh, north India.

Transmission of Japanese encephalitis virus in Culex pseudovishnui & C. tritaeniorhynchus mosquitoes.

Studies on the transovarial transmission of Japanese encephalitis virus (JEV) by orally infected female C. pseudovishnui showed that these mosquitoes were capable of transmitting JEV by bite to susceptible hosts. Infected females also transmitted the virus vertically to its first generation progeny. In another experiment, C. tritaeniorhynchus was also shown capable of transmitting the virus vertically to its first generation progeny. However, there was no apparent difference in transovarial transmission capabilities of these two species in orally infected mosquitoes.