Kashi N. Prasad

Comparative Evaluation of Fungal, Tubercular, and Pyogenic Brain Abscesses with Conventional and Diffusion MR Imaging and Proton MR Spectroscopy

BACKGROUND AND PURPOSE: It is difficult to differentiate the cause of brain abscesses with the use of CT and MR imaging. We did a comparative evaluation of pyogenic, tubercular, and fungal brain abscesses by using conventional, diffusion-weighted imaging (DWI), and proton MR spectroscopy (PMRS) with an aim to define the unique features that may differentiate among the pyogenic, tubercular, and fungal brain abscesses. MATERIALS AND METHODS: We performed a retrospective analysis on 110 patients with surgically proved brain abscesses. Imaging studies included T2, T1, postcontrast T1, DWI, and PMRS. Apparent diffusion coefficient (ADC) of the wall and cavity of the abscesses were quantified. The morphologic, physiologic, and metabolite features of pyogenic (n = 91), tubercular (n = 11), and fungal (n = 8) abscesses were compared. RESULTS: The pyogenic abscesses had smooth (55/91) and lobulated (36/91) walls, whereas the tubercular abscesses had smooth (4/11), lobulated (6/11), or crenated walls (1/11) with no intracavitary projections. The fungal abscesses showed irregular walls (lobulated 4/8, crenated 4/8) with intracavitary projections (8/8). The wall as well as the cavity showed low ADC in the pyogenic and tubercular abscesses. In the fungal abscesses, the wall and projections showed low ADC (8/8); however, the cavity itself showed high ADC (8/8). PMRS showed cytosolic amino acids (89/91), acetate (25/91), and succinate (18/91) in the pyogenic abscesses, whereas lipid/lactate (11/11) was seen in the tubercular abscesses. The fungal abscesses showed lipid (4/8), lactate (7/8), amino acids (4/8), and multiple peaks between 3.6 and 3.8 ppm assigned to trehalose (5/8). CONCLUSION: Based on the morphologic, ADC, and metabolite information, it may be possible to differentiate among the pyogenic, tubercular, and fungal brain abscesses.

Role of Diffusion-weighted Imaging and In Vivo Proton Magnetic Resonance Spectroscopy in the Differential Diagnosis of Ring-enhancing Intracranial Cystic Mass Lesions

Objectives: Proton magnetic resonance spectroscopy (PMRS) and diffusion-weighted imaging (DWI) were compared to determine which technique is more effective in the differential diagnosis of cystic intraparenchymal ring-enhancing lesions with variable perifocal edema. Methods: Fifty-two patients (abscesses [n = 29], tumor cysts [n = 20], and benign cysts [n = 3]) formed the basis for comparative evaluation in this study. The criteria for abscess diagnosis were apparent diffusion coefficient (ADC) values less than 0.9 ± 1.3 × 10−3 mm2/s and presence of lactate cytosolic amino acids (AAs) with/without succinate, acetate, alanine, and glycine on PMRS. Criteria for nonabscess cyst identification were ADC values of 1.7–3.8 × 10−3 mm2/s and presence of lactate and choline on PMRS. On the basis of these criteria, patients were categorized into abscess (n = 29) and nonabscess (n = 23) groups. Sensitivity and specificity of PMRS and DWI with respect to the final diagnosis were calculated based on the efficacy of these techniques. Results: Apparent diffusion coefficient values in 21 patients with abscesses were observed within the range of defined criteria, whereas in 8 patients, ADC values were beyond the range of defined criteria. Lactate and AAs with or without other metabolites were observed in 25 of 29 cases of abscesses on PMRS. In the nonabscess group, ADC values of cystic lesions in all patients were consistent with respect to the defined criteria. Only lactate was seen in 14 of 23 patients, whereas both lactate and choline were visible in 6 patients. In 3 patients with neurocysticercosis, AAs (n = 2), lactate (n = 3), acetate (n = 1), succinate (n = 3), choline (n = 2), and alanine (n = 3) were seen. The sensitivity of DWI and PMRS for differentiation of brain abscess from nonbrain abscess was 0.72 and 0.96, respectively, whereas the specificity was 1 for both techniques. Conclusion: Demonstration of restricted diffusion on DWI with reduced ADC is highly suggestive of brain abscess; however, in the absence of restriction, PMRS is mandatory to distinguish brain abscesses from cystic tumors.

Biological correlates of diffusivity in brain abscess

Restricted diffusion in brain abscess is assumed to be due to a combination of inflammatory cells, necrotic debris, viscosity, and macromolecules present in the pus. We performed diffusion‐weighted imaging (DWI) on 41 patients with proven brain abscesses (36 pyogenic and five tuberculous), and correlated the apparent diffusion coefficient (ADC) from the abscess cavity with viable cell density, viscosity, and extracellular‐protein content quantified from the pus. On the basis of the correlation between cell density and ADC in animal tumor models and human tumors in the literature, we assumed that the restricted ADC represents the cellular portion in the abscess cavity. We calculated restricted and unrestricted lesion volumes, and modeled cell density over the restricted area with viable cell density per mm3 obtained from the pus. The mean restricted ADC in the cavity (0.65 ± 0.01 × 10–3 mm2/s) correlated inversely with restricted cell density in both the pyogenic (r = −0.90, P = <0.05) and tuberculous (0.60 ± 0.04 × 10–3 mm2/s, r = −0.94, P = <0.05) abscesses. We conclude that viable cell density is the main biological parameter responsible for restricted diffusion in brain abscess, and it is not influenced by the etiological agents responsible for its causation. Magn Reson Med, 2005.

Human cysticercosis and Indian scenario: a review

Cysticercosis, caused by Taenia solium larva is a major public health problem, especially in the developing world and neurocysticercosis (NCC) is considered to be the most common parasitic infestation of the central nervous system. NCC is identified as the single most common cause of community acquired active epilepsy; 26.3% to 53.8% active epilepsy cases in the developing world including India and Latin America are due to NCC. It is also becoming more common in the developed world because of increased migration of people with the disease or Taenia solium carriers and frequent travel to the endemic countries. It is estimated that three quarters of the estimated 50 million people with active epilepsy live in the poor countries of the world. Recent Indian studies using neuroimaging techniques suggest that the disease burden in India surpasses many other developing countries. Hence it is important to know the epidemiology, pathogenesis and diagnostic criteria so as to assess the disease burden and adopt interventional strategies for its control. Literature search was done for this review with special emphasis on Indian studies to create awareness about the disease in India, since cysticercosis is preventable and potentially eradicable.

Fungal peritonitis in patients on continuous ambulatory peritoneal dialysis: a single centre Indian experience

BACKGROUND Fungal peritonitis (FP) is a serious complication in patients on continuous ambulatory peritoneal dialysis (CAPD). We reviewed our FP cases to analyse the causative agents and possible risk factors in relation to FP and its outcome and mortality. METHODS Records of all FP cases were reviewed. FP was diagnosed based on effluent cell count and positive fungal culture in suitable media. RESULTS Between October 1993 and November 2001, 261 patients underwent CAPD. FP was detected in 28 patients, one episode in each patient (14.3% of the total peritonitis episodes). Candida species and dematiaceous fungi+/-Candida species were responsible for 89.3 and 10.7% of episodes, respectively. Patients with preceding bacterial peritonitis (BP) developed FP more frequently (25.6%) than de novo cases (2.9%) (P<0.0001) and lower proportion of them continued CAPD (8.6% vs. 60%; P=0.007). Mortality in patients having abdominal pain with and without fever, and catheter in situ was significantly higher than in those patients who did not have these risk factors (9/11 vs. 6/17, P=0.01; 13/17 vs. 2/11, P=0.003; 6/6, vs. 9/22, P=0.01, respectively). CONCLUSIONS Higher proportion of our patients had FP; preceding BP was a significant risk factor for development of FP and technique failure. Abdominal pain+/-fever in patients and catheter in situ were identified as risk factors associated with mortality.

Changing microbiological profile of pathogenic bacteria in diabetic foot infections: time for a rethink on which empirical therapy to choose?

Aims/hypothesisWe studied the bacterial aetiology and antibiotic sensitivity pattern of diabetic foot ulcers in India.MethodsRecords of 447 hospitalised patients between 1991 and 2008 were retrospectively analysed between two time periods (before and after 1999) to compare bacterial aetiology and antimicrobial sensitivity patterns. The first three consecutive cultures from the same wound during treatment were evaluated.ResultsOf 1,632 cultures, 66% were polymicrobial, 23% monomicrobial and 11% sterile. In the monomicrobial group, 14% (n = 228) of cultures were Gram-negative, whereas 9% (n = 147) were Gram-positive. The most common pathogens in the first culture were Pseudomonas aeruginosa (20.1%), Staphylococcus aureus (17.2%) and Escherichia coli (16.3%). Results for the third cultures showed persistence of P. aeruginosa (15.3%) and E. coli (14.2%). Gram-negative isolates dominated over Gram-positive ones (25.3% vs 15.1%, p < 0.05). Antibiotic sensitivity patterns before and after 1999 were: piperacillin–tazobactam 74% vs 66% (p < 0.005), imipenem 77% vs 85% (NS), cefoperazone–sulbactam 47% vs 44% (p < 0.005), amikacin 62% vs 78% (NS), ceftriaxone 41% vs 36% (p < 0.005), amoxicillin–clavulanate 51% vs 43% (p < 0.05) and clindamycin 43% vs 36% (p < 0.005), respectively.Conclusions/interpretationUnlike in the West, in India Gram-negative bacteria were found to have always been dominant in the wounds of patients with diabetic foot infections. Infection with polymicrobial multidrug-resistant Gram-negative bacilli is common. The policy of empirical antimicrobial therapy at tertiary care needs to be changed.

In Vivo Proton MR Spectroscopy Evaluation of Pyogenic Brain Abscesses: A Report of 194 Cases

BACKGROUND AND PURPOSE: The combination of nonspecific clinical findings and similarities in morphologic appearances on imaging often makes it difficult to distinguish abscesses from other brain lesions. We present a retrospective analysis of in vivo 1H-MR spectroscopy data for characterization of the etiology of the brain abscess based on the established criteria and demonstrate the sensitivity and specificity of metabolite markers assigned to specific bacterial groups defined by the microbial culture in 194 patients. MATERIALS AND METHODS: Conventional MR imaging and in vivo 1H-MR spectroscopy data were evaluated from patients with pyogenic brain abscesses, with ages ranging from 3 to 60 years. Imaging and 1H-MR spectroscopy were performed on a 1.5T scanner. After MR imaging was performed and analyzed, pus aspirates were obtained in all patients. The causative organisms were confirmed by pus cultures. RESULTS: Resonance of AAs with or without other metabolites on in vivo 1H-MR spectroscopy was observed in 80% of abscesses, with a sensitivity and specificity of 0.72 and 0.30, respectively. Most obligate anaerobes and some facultative anaerobes showed the presence of Lac/Lip, AAs, and Ac with or without Suc. Mostly obligate aerobes or facultative anaerobes showed the presence of Lac and AAs, with or without lipids. CONCLUSIONS: The presence of AAs on in vivo 1H-MR spectroscopy is a sensitive marker of pyogenic abscess, but its absence does not rule out a pyogenic etiology. The presence of Ac with or without Suc favors an anaerobic bacterial origin of the abscess; however, this may also be seen in some of the abscesses secondary to facultative anaerobes.

Association of the novel aminoglycoside resistance determinant RmtF with NDM carbapenemase in Enterobacteriaceae isolated in India and the UK

OBJECTIVES 16S rRNA methyltransferases are an emerging mechanism conferring high-level resistance to clinically relevant aminoglycosides and have been associated with important mechanisms such as NDM-1. We sought genes encoding these enzymes in isolates highly resistant (MIC >200 mg/L) to gentamicin and amikacin from an Indian hospital and we additionally screened for the novel RmtF enzyme in 132 UK isolates containing NDM. METHODS All highly aminoglycoside-resistant isolates were screened for armA and rmtA-E by PCR, with cloning experiments performed for isolates negative for these genes. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry was used to determine the methylation target of the novel RmtF methyltransferase. RmtF-bearing strains were characterized further, including susceptibility testing, PFGE, electroporation, PCR-based replicon typing and multilocus sequence typing of rmtF-bearing plasmids. RESULTS High-level aminoglycoside resistance was detected in 140/1000 (14%) consecutive isolates of Enterobacteriaceae from India. ArmA, RmtB and RmtC were identified among 46%, 20% and 27% of these isolates, respectively. The novel rmtF gene was detected in 34 aminoglycoside-resistant isolates (overall prevalence 3.4%), most (59%) of which also possessed a bla(NDM) gene; rmtF was detected in 6 NDM producers from the UK. It was found on different plasmid backbones. Four and two isolates showed resistance to tigecycline and colistin, respectively. CONCLUSIONS RmtF was often found in association with NDM in members of the Enterobacteriaceae and on diverse plasmids. It is of clinical concern that the RmtF- and NDM-positive strains identified here show additional resistance to tigecycline and colistin, current drugs of last resort for the treatment of serious bacterial infections.

Differences in virulence attributes between cytolethal distending toxin positive and negative Campylobacter jejuni strains.

Campylobacter jejuni is a common gastrointestinal bacterial pathogen. Although cytolethal distending toxin (CDT) is proposed to be an important virulence determinant of this pathogen, how CDT(+) and CDT(-) strains differ in their biological properties remains largely unknown. The virulence properties of CDT(+) and CDT(-) strains were studied on HeLa cells and in the suckling mouse model. Presence of the cdtB gene in Campylobacter species was determined by PCR. Five each of CDT(+) and CDT(-) C. jejuni strains were subjected to adherence, invasion and cytotoxicity assay on the HeLa cell line. Bacterial culture supernatants with and without CDT activity were inoculated intragastrically into 2-day-old suckling mice. The mice were sacrificed within 48 h. Histopathological examination of stomach, jejunum, ileum and colon was performed by haematoxylin/eosin staining. cdtB was detected in 88 % and 14 % of C. jejuni and Campylobacter coli strains, respectively. CDT(+) C. jejuni strains adhered to and invaded HeLa cells in significantly higher numbers than CDT(-) strains [CDT(+) vs CDT(-), adherence 2.7 x 10(4)+/-3.5 x 10(4) vs 2.7 x 10(2)+/-1.9 x 10(2); invasion 1.0 x 10(3)+/-1.3 x 10(3) vs 1.4 x 10(1)+/-3.1 x 10(1); P<0.01]. Culture supernatants of all CDT(+) strains demonstrated CDT activity on HeLa cells. Mice inoculated with supernatant containing CDT activity had moderate to severe pathology in different parts of their gastrointestinal tract, with the colon being the major target. Mice inoculated with supernatant lacking CDT activity showed no significant pathology in the gastrointestinal tract. The results demonstrate that CDT(+) C. jejuni strains adhere to and invade epithelial cells more efficiently than CDT(-) strains. CDT is responsible for intestinal pathology and the colon is the major target.

Prevalence and molecular characterisation of New Delhi metallo-β-lactamases NDM-1, NDM-5, NDM-6 and NDM-7 in multidrug-resistant Enterobacteriaceae from India.

The growing prevalence of carbapenem resistance in Enterobacteriaceae worldwide is a major concern. New Delhi metallo-β-lactamase (NDM)-mediated carbapenem resistance has been identified in Enterobacteriaceae from numerous countries including those of the Indian subcontinent. Currently, seven NDM β-lactamase variants (NDM-1 to -7) have been identified. This study evaluated the detection and molecular characterisation of NDM variants in Enterobacteriaceae at a tertiary care hospital in India. A total of 464 isolates were tested; 57 (12.3%) were resistant or showed reduced susceptibility to imipenem and meropenem. All carbapenem-resistant isolates were blaNDM-positive by PCR, but 13 isolates bore variants that differed in sequence from blaNDM-1. NDM-5, NDM-6 and NDM-7 were identified in two, eight and three isolates, respectively. blaNDM variants were located on plasmids of >100kb with IncF, IncA/C and untypeable replicon types. Genes encoding the 16S rRNA methyltransferases RmtB, RmtC and ArmA as well as those for AmpC β-lactamases were also located on the same plasmids as blaNDM in different combinations. The prevalence of NDM-5 to -7 variants was significantly higher in Escherichia coli (P=0.015) and they were more frequently isolated from the urology ward (P=0.037) than NDM-1. The mortality rate was comparable between patients infected with isolates positive for blaNDM-1 and blaNDM variants [25% (11/44) vs. 23% (3/13)]. Expression of blaNDM variants in E. coli using the same promoter showed that NDM-7 conferred higher resistance to imipenem. The diverse genotypic features of blaNDM indicate rapid evolution of NDM resulting from their wide spread in the Indian subcontinent.