Pulmonary Mycobacterium kansasii disease in immunocompetent host: Treatment outcomes with short‑course chemotherapy.

Mycobacterium kansasii, most virulent of all atypical mycobacteria, causes pulmonary disease identical to the disease caused by Mycobacterium tuberculosis. Early identification of the species and prompt initiation of treatment for M. kansasii is necessary to prevent morbidity and mortality due to this disease. This case series highlights the similarity in the clinical presentation of both M. tuberculosis and M. kansasii and response to direct observation of short‑course chemotherapy with rifampicin, in the management of pulmonary M. kansasii disease. Larger studies are required to evaluate the long‑term effect of short‑course chemotherapy, especially use of moxifloxacin, in the management of pulmonary M. kansasii disease.

Antigen sequence typing of outer membrane protein (fetA) gene of Neisseria meningitidis serogroup A from Delhi & adjoining areas.

Background & objectives: Meningitis caused by Neisseria meningitidis is a fatal disease. Meningococcal meningitis is an endemic disease in Delhi and irregular pattern of outbreaks has been reported in India. All these outbreaks were associated with serogroup A. Detailed molecular characterization of N. meningitidis is required for the management of this fatal disease. In this study, we characterized antigenic diversity of surface exposed outer membrane protein (OMP) FetA antigen of N. meningitidis serogroup A isolates obtained from cases of invasive meningococcal meningitis in Delhi, India. Methods: Eight isolates of N. meningitidis were collected from cerebrospinal fluid during October 2008 to May 2011 from occasional cases of meningococcal meningitis. Seven isolates were from outbreaks of meningococcal meningitis in 2005-2006 in Delhi and its adjoining areas. These were subjected to molecular typing of fetA gene, an outer membrane protein gene. Results: All 15 N. meningitides isolates studied were serogroup A. This surface exposed porin is putatively under immune pressure. Hence as a part of molecular characterization, genotyping was carried out to find out the diversity in outer membrane protein (FetA) gene among the circulating isolates of N. meningitidis. All 15 isolates proved to be of the same existing allele type of FetA variable region (VR) when matched with global database. The allele found was F3-1 for all the isolates. Interpretation & conclusions: There was no diversity reported in the outer membrane protein FetA in the present study and hence this protein appeared to be a stable molecule. More studies on molecular characterization of FetA antigen are required from different serogroups circulating in different parts of the world.

Factors predicting 'time to distant metastasis' in radically treated head and neck cancer.

Context: Various studies have shown the important risk factors for distant metastasis in head and neck cancer (HNC) which are present in most of the patients in developing countries. Identification of factors on the basis of time to distant metastasis (TDM) can help in future trials targeting smaller subgroups. Aims and Objectives: To identify the factors that predict TDM in radically treated HNC patients. Settings and Design: Retrospective audit. Materials and Methods: Retrospective audit of the prospectively maintained electronic database of a single HNC radiotherapy clinic from 1990 to 2010 was done to identify radically treated patients of HNC who developed distant metastasis. Univariate and multivariate analysis were done to identify baseline (demographic, clinical, pathological, and treatment) factors which could predict TDM, early time to metastasis (ETM; <12 months), intermediate time to metastasis (ITM; 12-24 months), and late time to metastasis (LTM; >2 years) using Kaplan Meier and Cox regression analysis, respectively. Results: One hundred patients with distant metastasis were identified with a median TDM of 7.4 months; 66 had ETM, 17 had ITM, and 17 had LTM. On multivariate analysis, the nodal stage 2-3 (N2/3) was the only baseline factor independently predicting TDM, ETM, and ITM, whereas none of the baseline factors predicted LTM. Conclusions: Higher nodal burden (N2/3) is associated with both ETM and ITM, and calls for aggressive screening, systemic therapy options, and surveillance. It is difficult to predict patients who are at a risk of developing LTM with baseline factors alone and evaluation of biological data is needed.

Microbial colonization of Provox voice prosthesis in the Indian scenario.

INTRODUCTION: Tracheoesophageal speech using the voice prosthesis is considered to be the “gold standard” with success rates as high as 90%. Despite significant developments, majority eventually develop dysfunction due to microbial deterioration. We did a pilot study of 58 laryngectomy patients who developed prosthesis dysfunction. MATERIALS AND METHODS: A total of 58 laryngectomy patients who had their dysfunctional prosthesis removed were included in this study. Dysfunctional prostheses were removed and examined. Esophageal and tracheal flanges were examined separately. After obtaining pure fungal and bacterial cultures, the yeast strains were identified. Bacteria were identified with the light microscope and gram staining. We analyzed prosthesis lifespan and probable factors affecting it. RESULTS: Central leak was found in 43% cases while in 57% peri‑prosthetic leakage was the most common reason for prosthesis replacement. Microbial analysis revealed a combination of yeast and bacteria in approximately 55% culture samples. Out of these, almost 90% had the presence of single yeast species with bacteria. Pure fungal culture was identified in rest of the 45% cultures while none detected pure bacterial forms. Candida tropicalis was the solitary yeast in 81% while Candida albicans was seen in 10% as the solitary yeast. Bacterial isolates revealed Klebsiella pneumonia in 19%, Escherichia coli in 8% while Staphylococcus aureus was grown in 1% cultures. The consumption of curd (P = 0.036, 95% confidence intervals [CI]: 2.292‑64.285) to have a significant correlation of the mean prosthesis lifespan. Consumption of curd (P = 0.001, 95% CI: 0.564‑2.008) and history of prior radiotherapy (P = 0.015, 95% CI: 0.104‑0.909) had a significant bearing on the Provox prosthesis lifespan. CONCLUSIONS: Candida is the most common organism grown on voice prosthesis in Indian scenario. Consumption of curd and history of prior radiotherapy significantly affect Provox prosthesis lifespan.

Delay in seeking specialized care for oral cancers: Experience from a tertiary cancer center.

OBJECTIVE: Advanced oral cancers are a challenge for treatment, as they require complex procedures for excision and reconstruction. Despite being occurring at a visible site and can be detected easily, many patients present in advanced stages with large tumors. Timely intervention is important in improving survival and quality of life in these patients. The aim of the present study was to find out the causes of delay in seeking specialist care in advanced oral cancer patients. MATERIALS AND METHODS: A prospective questionnaire based study was done on 201 consecutive advanced oral squamous cancer patients who underwent surgery at our hospital. All patients had either cancer of gingivobuccal complex (GBC) or tongue and had tumors of size more than 4 cm (T3/T4) and were treatment naïve at presentation. RESULTS: Even though most patients observed abnormal lesions in their mouth, majority delayed the decision to visit a physician early. A significant percentage of patients (50%) also reported a delayed diagnosis by the primary care physician before being referred to a tertiary care center for definitive treatment. The average total duration from symptoms to treatment was 7 months. CONCLUSION: The main reasons of this delay in receiving treatment were due to patients themselves (primary delay) or due to time taken by the primary physician to diagnose the condition (secondary delay). Oral self-examination can be helpful in detecting oral cancers early.

Neo-adjuvant chemotherapy in advanced hypopharyngeal carcinoma.

Objective: The aim of this retrospective study was to find out the role of neo-adjuvant chemotherapy (NACT) in changing the management and outcome of advanced hypopharyngeal cancer patients. Materials and Methods: This is a retrospective analysis of 59 treatment naïve, advanced hypopharyngeal cancer patients presenting to our tertiary care center from April 2010 to October 2011. NACT was given as two (platinum with taxane) or three drug with (platinum, taxane with 5-flurouracil [5 FU]) as 3 weekly regimen with cisplatin and docetaxel as 75 mg/m 2 each, 5-FU as 1000 mg/m 2 . NACT was either given with the intent of achieving: (1) surgical resection (extensive soft tissue disease, oropharyngeal involvement, extensive disease with cartilage erosion) or (2) organ preservation (Bulky disease with inner cartilage erosion, exolaryngeal disease without cartilage erosion, large N3 nodes). Results: The mean age of this population was 55 years. Most (83%) of the patients had pyriform sinus (PFS) involvement. 69% patients had Stage IVa disease, 21% Stage IVb and 10% Stage III. The overall response rate was 66%, including 06% complete responses and 60% partial responses. Following NACT, resectability was achieved in 30% (10/33) and organ preservation protocol was planned after NACT in 73% (19/26) patients. The main toxicities were neutropenia (grade 3, 4, 04%; febrile neutropenia, 4%), mucositis 5%, diarrhea 5%. The median progression free survival was 20 months. Conclusions: NACT can be useful in patients with oropharyngeal involvement to achieve surgical resection and larynx preservation in patients with bulky T3 disease.

Rapid culture diagnosis of tuberculous lymphadenitis from a tertiary care centre in an endemic nation: Potential and pitfalls.

In spite of low sensitivity and specificity, standard diagnostic algorithm recommends fine needle aspiration cytology (FNAC) and direct microscopic screening for acid-fast bacilli (AFB) for the routine diagnosis of tuberculous lymphadenopathy (LNTB). In this study, the diagnostic utility of liquid broth based automated culture (BacT/ALERT 3D) technique was assessed in comparison with conventional techniques in 89 clinically suspected tubercular lymphadenitis patients. 60% (n = 53) were positive by FNAC and 38.4% (n = 34) demonstrated AFB in smear examination. BacT/ALERT yielded isolation in 43.1% (n = 38) aspirates, confirming tubercular aetiology. We also found six paediatric culture-positive cases which showed negative outcome by both FNAC and smear. Thus, we conclude that culture by BacT/ALERT, may be used for faster yield of Mycobacteria in LNTB, especially in children. Additionally, this could also be used as a platform for further differentiation of Mycobacterium tuberculosis from non-tuberculous mycobacteria (NTM) infection and for testing of anti-tubercular chemotherapeutic agents whenever drug resistance is suspected.

Assessment of trends of ofloxacin resistance in Mycobacterium tuberculosis.

Purpose: Ofloxacin (OFX) is one of the potent fluoroquinolone (FQ) recommended to treat MDR-TB. Over a decade, the preexposure of this drug for the treatment of other bacterial infections has resulted in acquisition of FQ resistance among Mycobacterium tuberculosis strains. Considering this possibility, a study was undertaken in a tertiary care center in the capital city (India) to assess the drug resistance trends of OFX among susceptible and multidrug resistant (MDR) strains of M. tuberculosis. Materials and Methods: A total of 102 M. tuberculosis isolates (47 susceptible to first-line drugs and 55 MDR isolates) were screened for susceptibility testing of OFX with a critical concentration of 2 μg/ml by Lowenstein Jensen (LJ) proportion method. Results: The results showed 40 (85.1%) isolates among 47 susceptible isolates and 34 (61.8%) isolates among 55 MDR isolates, were found to be susceptible to OFX. Fisher's exact test showed significant P-value (0.0136) demonstrating 1.377 fold (95% confidence interval) increased risk to become resistant to OFX than susceptible isolates. These finding shows decreased OFX susceptibility is not only limited to MDR isolates but also increasingly seen in susceptible strains as a result of drug abuse. Conclusions: Our finding were not alarming, but highlights the general risk of acquiring resistance to OFX, jeopardizing the potential for these drugs to be used as second-line anti-TB agents in the management of drug-resistant TB and creating incurable TB strains.

Evaluation of Nucleic Acid Probe for Rapid Identification of Mycobacterium tuberculosis Complex in Extra-Pulmonary Culture Isolates.

Patients infected with Non-tuberculous mycobacteria (NTM) usually do not respond to conventional anti-tubercular treatment and are misdiagnosed as infection with multi-drug resistant strains of mycobacterium tuberculosis (M.tb) due to lack of correct species identification, particularly in the developing countries like India. One of the challenges faced by clinicians in the treatment of tuberculosis is the absence of an easy, reliable and rapid identification tool that can accurately differentiate disease caused by M.tb complex from NTM. Keeping this in consideration, the performance of species specific nucleic acid probe i.e. Accuprobe was assessed and compared with conventional niacin production, nitrate reductase assay techniques for identification of M.tb complex in 80 mycobacterial isolates obtained from different extra - pulmonary sites. Accuprobe identified 62 isolates (77.5%) as M. tuberculosis complex and remaining 18 isolates (22.5%) as NTM whereas 64 isolates (80%) were identified as M.tb and rest 16 (20%) were interpreted as NTM by conventional biochemical techniques. The overall agreement between both techniques was 96.9% The sensitivity, specificity, positive predictive value(PPV) and negative predictive value (NPV) shown by accuprobe were 96.9%, 100%, 96.9%, and 88.9% respectively. Thus, accuprobe has showed impressive sensitivity and specificity giving results in <3 hrs from culture-positive isolates and have sure edge over conventional biochemical methods which are, nonetheless, labour intensive and cumbersome to perform thus delaying prompt mycobacterial identification.

The use of E-test for the drug susceptibility testing of Mycobacterium tuberculosis - A solution or an illusion.

Aim: To evaluate E-test as a tool for rapid determination of drug susceptibility against the conventional LJ method focusing on reliability, expense, ease of standardization and performance of the technique in low resource settings. Materials and Methods: A total of 74 clinical isolates (2004-2005) of Mycobacterium tuberculosis were tested using E-test for susceptibility to streptomycin (STM), isoniazid (INH), rifampicin (RIF) and ethambutol (EMB) by E-strip and LJ (LJPM) proportion methods. Results: The LJPM method, the gold standard, detected resistance against STM in 16.2%, INH in 40.5%, RIF in 18.9% and EMB in 27% cases. In comparison, the resistance values showed by E-test was 66.67% for STM, 57.14% for INH 71.43% for RIF and 80% for EMB. The susceptible correlation was 90.32% for STM, 73.91% for INH, 93.33% for RIF and 59.26% for EMB. E-test correctly identified only eight of the 12 (66.6%) MDR isolates and wrongly identified four isolates which were not MDR. The overall agreement between the two methods was only 48.6%. Resistant isolates showed false positive resistance observed while using E-strip towards all the drugs. Conclusion: E-strips are not quite feasible as a replacement for LJ-proportion method on a large scale due to high risk of cross contamination, laboratory infection, expense associated with it and high false positive resistance observed to all first line drugs. However, the good correlation observed for RIF between the two methods indicates that E-test could contribute to the role in rapid screening of MDR TB isolates as rifampicin mutations are invariably observed in MDR TB isolates.

Role of enteric fever in ileal perforations: an overstated problem in tropics?

PURPOSE: To determine the role of enteric fever in ileal perforations. METHODS: A prospective cohort of 47 patients of ileal perforation was subjected to clinical examination and investigations for APACHE II scoring. Blood, ulcer edge biopsy, mesenteric lymph node and peritoneal aspirate were subjected to culture to determine the predominant aerobic bacterial isolate and its antibiogram. RESULTS: Seven patients (14.9%) required intensive care and seven (14.9%) developed septicaemia. Mortality was 17%. Highest isolation rate was seen in ulcer edge (70.2%) followed by lymph node (66%) culture. The bacterial spectrum was Escherichia coli (23.4%), Enterococcus faecalis (21.3%), Salmonella enterica serovar Typhi (6.3%), Salmonella enterica serovar Paratyphi A (4.2%), etc. CONCLUSIONS: Enteric fever organisms are not the predominant causative agents of ileal perforations. Culture of ulcer edge biopsy, lymph node is crucial for aetiological diagnosis. The use of APACHE II triaging and prescription of antimicrobials based on the local pattern of susceptibility profile of the aetiological agent is recommended.

Clinical and mycological profile of cryptococcosis in a tertiary care hospital.

This study examined the extent of cryptococcosis in clinically diagnosed cases of meningitis in HIV-1 seropositive and apparently immunocompetent patients. One hundred and forty-six samples, obtained from 126 chronic meningitis patients comprised of cerebrospinal fluid (CSF), blood, sputum and urine. The samples were processed by standard microbiological procedures. Cryptococcal isolates were identified by microscopy, cultural characteristics, melanin production on niger seed agar and hydrolysis of urea. The isolates were further speciated on cannavanine glycine bromothymol blue (CGB) media. Cryptococcal antigen detection of CSF samples was performed by latex agglutination test (LAT). Minimum inhibitory concentration (MIC) of amphotericin B for the isolates was also tested. Cryptococcosis was diagnosed in 13 patients (eight HIV-1 seropositive and five apparently immunocompetent). Cryptococcus neoformans var. neoformans was the predominant isolate. Cryptococcal antigen was detected in all, whereas microscopy could detect yeast cells in nine patients. The isolates were sensitive to amphotericin B. CD4 cell counts ranged from 8 to 96/cu mm. The study concludes that all CSF samples with clinical diagnosis of subacute and chronic meningitis should be subjected to tests for detection of Cryptococcus in clinical laboratory irrespective of the immune status.

Eumycetoma pedis due to Exophiala jeanselmei.

A case of eumycetoma of foot in an 8-year old male child was clinically diagnosed as chronic osteomyelitis and was microbiologically confirmed as eumycetoma. The case is being reported for its uncommon clinical presentation and etiological agent, Exophiala jeanselmei. The patient recovered completely after treatment with ketoconazole.

Characterization and changing minimum inhibitory concentration (MIC) of Acinetobacter species from a tertiary care setup.

128 isolates of Acinetobacter species from admitted and outdoor patients were subjected to biotyping and resistotyping. Resistance phenotype analysis included nine antibiotics and two betalactam inhibitor combination drugs. In 100 strains of Acinetobacter spp. ciprofloxacin, amikacin, cefotaxime and cefepime minimum inhibitory concentration (MIC) was done by agar dilution using NCCLS 2002 criteria. In forty-nine isolates MIC level was determined by E-strip also. Extended spectrum beta lactamase (ESBL) production was detected by double disc synergy technique. Inducible beta lactamases (IBL's) were detected by disc approximation method. The relationship between biotypes and resistance phenotype was analyzed. Majority of isolates (93.75%) were from admitted patients. The biotyping revealed Acinetobacter calcoaceticus-Acinetobacter baumannii complex (87.2%) to be the predominant species and they were isolated from tracheal aspirates of patients with ventilator associated pneumonia. By Kirby Bauer disc diffusion antimicrobial sensitivity testing Acinetobacter spp. were most sensitive to the combination of drug cefoperazone-sulbactam (95.6%) followed by meropenem (94.6%), piperacillin-tazobactam (92.6%). On screening incidence of Imipenem Nonsensitive Acinetobacter spp. (INSA) was (5.4%). Acinetobacter spp. were typable by six resistance phenotypes and six biotypes. Most common (66.6%) resistant phenotype of A. calcoaceticus-A. baumannii complex was susceptible to cefoperazone-sulbactam and or meropenem and or piperacillin-tazobactam. ESBL production was seen in 6% and IBL (Inducible Beta Lactamase) production was seen in 7% of Acinetobacter spp. The MIC90 for ciprofloxacin was =256 microg/ml, cefotaxime 512 microg/ml, cefepime 512 microg/ml, and amikacin 32 microg/ml. Multidrug resistance was seen in more than 90% of A. calcoaceticus-A. baumannii complex and 20% of Acinetobacter lwoffii. Acinetobacter spp. has other emerging novel mechanism of resistance that requires continuous research. Simpler, reproducible and reliable methods of biotyping and their subsequent correlation with resistotyping are more cost effective than molecular methods, which are available only in reference laboratories.

Morbidity predictors in ischemic stroke.

BACKGROUND: Although ischemic CVA is one of the leading causes for death and disability, parameters for predicting long-term outcome in such patients have not been clearly delineated, especially in the Indian context. METHODS: A prospective hospital-based study of 105 patients of ischemic stroke, focal neurological deficits and functional score was assessed and the C-reactive protein level (CRP) was measured. A follow-up was done at 5 days and at 6 months and outcome variable was the functional status at 6 months using Barthel Index of Activities of Daily Living. Accordingly, patients were grouped into 3 - Barthel Index < 41: Severely disabled, Barthel Index 41-60: Moderately disabled and Barthel Index > 60: Mildly disabled. RESULTS: At admission, if upper limb power was less than Medical Research Council (MRC) grade 4, or aphasia was present or CRP assay was positive, then at 6 months, these patients most likely belonged to the severely disabled group. If upper limb or lower limb power was greater than MRC grade 3 or there was no aphasia or conjugate gaze deviation or CRP assay was negative, these patients most likely belonged to the mildly disabled group at 6 months. Follow-up rate was 86%. CONCLUSION: Patients can be stratified according to the predicted prognosis. The treatment and rehabilitation can be properly planned and strictly adhered to in patients predicted to have worse prognosis.