Drug-resistant organisms are common in fecal surveillance cultures, predict bacteremia and correlate with poorer outcomes in patients undergoing allogeneic stem cell transplants.

BACKGROUND: With the increasing incidence of multidrug-resistant (MDR) organisms and high mortality rates associated with these infections, we describe the spectrum of the major drug-resistant pathogens identified in fecal surveillance, and re-visit the use of fecal surveillance in predicting infection with these organisms post-allogeneic stem cell transplant. METHODS: Data from allogeneic stem cell transplant recipients with common drug-resistant strains of bacteria in fecal surveillance (Escherichia coli, Klebsiella spp., and Enterococcus spp.) were compared with recipients who did not have the same in fecal surveillance cultures. Baseline characteristics and post-transplant outcomes including similar drug resistance in blood cultures, severe sepsis, and 100-day transplant-related mortality were compared. Multivariate analysis using logistic regression model was used to determine independent predictors of outcome. RESULTS: In 232 transplants, the prevalence of common drug-resistant isolates in fecal surveillance cultures was 57.7% (134 out of 232 patients-with a single isolate in 115 and ≥2 isolates in the remaining 19 patients. A total of 164 drug-resistant isolates were obtained from 134 patients. Of the 164 isolates, 133 (81%) were positive for ESBL screening, 19 (11.5%) for carbapenem-resistant organisms (CRO) screening, 12 (7.3%) for VRE screening. Patients who had common drug-resistant pathogens detected in fecal surveillance have significantly higher subsequent blood culture positivity with drug resistance, as well as higher 100-day mortality. Factors influencing 100-day mortality included patient's age (P = .001), drug resistance positivity in blood (P < .001), drug resistance in fecal surveillance (P = .011), use of an alternate donor (other than fully matched sibling) (P < .001), GVHD grade 3-4 (P < .001), and severe sepsis (P < .001). On multivariate analysis, only use of an alternate donor (0.024), severe sepsis (P < .001), and grade 3-4 GVHD (P < .001) retained significance in predicting 100-day mortality. CONCLUSION: Organisms resistant to 3rd generation cephalosporins are frequently seen on fecal surveillance in the pre-transplant setting and are associated with a higher incidence of drug-resistant organisms in subsequent blood cultures (not limited to the same drug resistance pattern as seen in fecal surveillance). Drug-resistant organisms in fecal surveillance are associated with poorer outcomes following allogeneic stem cell transplant and may be used as a guide to identify patients at risk of subsequently developing a drug-resistant organism in blood.

Antimicrobial resistance, virulence & plasmid profiles among clinical isolates of Shigella serogroups.

Background & objectives: Bacillary dysentery caused by Shigella spp. remains an important cause of the crisis in low-income countries. It has been observed that Shigella species have become increasingly resistant to most widely used antimicrobials. In this study, the antimicrobial resistance, virulence and plasmid profile of clinical isolates of Shigella species were determined. Methods: Sixty clinical Shigella isolates were subjected to whole-genome sequencing using Ion Torrent platform and the genome sequences were analyzed for the presence of acquired resistance genes, virulence genes and plasmids using web-based software tools. Results: Genome analysis revealed more resistance genes in Shigella flexneri than in other serogroups. Among ß-lactamases, blaOXA-1was predominantly seen followed by the blaTEM-1B and blaEC genes. For quinolone resistance, the qnr S gene was widely seen. Novel mutations in gyr B, par C and par E genes were observed. Cephalosporins resistance gene, blaCTX-M-15 was identified and plasmid-mediated AmpC ß-lactamases genes were found among the isolates. Further, a co-trimoxazole resistance gene was identified in most of the isolates studied. Virulence genes such as ipaD, ipaH, virF, senB, iha, capU, lpfA, sigA, pic, sepA, celb and gad were identified. Plasmid analysis revealed that the IncFII was the most commonly seen plasmid type in the isolates. Interpretation & conclusions: The presence of quinolone and cephalosporin resistance genes in Shigella serogroups has serious implications for the further spread of this resistance to other enteric pathogens or commensal organisms. This suggests the need for continuous surveillance to understand the epidemiology of the resistance.

Performance of EAST in diagnosing inhalant allergens in children with allergic rhinitis.

The performance of enzyme linked immunosorbent assays (EAST) for identifying six indoor allergens was evaluated using skin prick test (SPT) as reference tests in 154 children with allergic rhinitis. Sensitivity of EAST ranged from 9% (cat) to 54% (HDM) with specificity of 74%(cockroach) to 100% (cat) with an agreement ranged from 58 to 86%. Cut off values â€‹> â€‹0.35 kU/L showed best sensitivity and specificity. Our findings agree with extant literature which suggests that the ability of EAST to determine the precipitating allergen is moderate. Assays for definitively identifying the inhalant allergen are currently not available.

EAST in Children with Allergic rhinitis: Experience from Indian Tertiary Centre.

Allergic rhinitis (AR) is recognized as a growing global health disease with considerable importance among children and adolescents. This study aims to study the clinical and sensitization profile of children with allergic rhinitis using EAST. All children presenting to pediatric ENT outpatient with a clinical diagnosis of AR were prospectively recruited. Detailed demographic and clinical history including self-reported allergens, predominant symptoms and associated comorbid conditions were obtained. Severity of symptoms was graded on a visual analogue scale. Specific Ig E antibodies to 20 inhalant allergens was measured using EAST (EUROIMMUN, Germany).The pattern of sensitization was analyzed with respect to age, symptoms, associated comorbid conditions and urbanization. We recruited 328 children with a clinical diagnosis of AR (Mean age 10.3 year, IQR 8-13 years) Nasal block was the predominant symptom across all age groups, sneezing became more troublesome during adolescence. In 191 children sera were tested for allergen specific IgE, 119 (62.3%) showed positive sensitization. The most common sensitization noted was for cockroach, followed by dust mite and pollens. Majority had polysensitization (73%). Those who were predominantly sneezers were more likely to be sensitized with indoor allergens (p < 0.05). Among the comorbid conditions, asthma and atopic dermatitis accounted for maximum non ENT physician visits. The pattern of sensitization did not vary with age, urbanization or comorbid condition. This study highlights the clinical and sensitization profile of children with AR in South East India. Various peculiarities of this community has been presented which needs further attention.

Geography and prevalence of rickettsial infections in Northern Tamil Nadu, India: a cross-sectional study.

Rickettsial infections and Q fever are a common cause of acute febrile illness globally. Data on the role of climate and altitude on the prevalence of these infections in lacking from Southern India. In this study, we determined the sero-prevalence of scrub typhus (ST), spotted fever (SF), murine typhus (MT) and Q Fever (QF) in 8 eight geographical regions of North Tamil Nadu by detecting IgG antibodies using ELISA. Totally we tested 2565 people from 86 localities. Among the 27.3% positives, approximately 5% were IgG positive for two or more infections. Sero-prevalence to rickettsioses and Q fever was highest for individuals from rural areas and increased with age (> 30 years). Those in the Nilgiris highlands (wetter and cooler) and Erode, which has the most land under irrigation, demonstrated the least exposure to rickettsioses and Q fever. Lowland plains (AOR: 8.4-22.9; 95% CI 3.1-55.3) and highland areas up to 1000 m (AOR: 6.1-10.3; 95% CI 2.4-23.9) showed the highest risk of exposure to scrub typhus. For spotted fever, the risk of exposure was highest in Jawadhi (AOR:10.8; 95% CI 2.6-44.3) and Kalrayan (AOR:16.6; 95% CI 4.1-66.2). Q fever positivity was most likely to be encountered in Salem (AOR: 5.60; 95% CI 1.01-31.08) and Kalrayan hills (AOR:12.3; 95% CI 2.9-51.6). Murine typhus risk was significant only in Tiruvannamalai (AOR:24.2; 95% CI 3.3-178.6). Our study suggests that prevalence of rickettsial infections and Q fever is low in areas which receive rainfall of ≥ 150 cm/year, with average minimum and maximum temperatures between 15 and 25 °C and elevation in excess of 2000 m. It is also less in well irrigated lowlands with dry climate. These preliminary findings need confirmation by active surveillance in these areas.

Purpura Fulminans and Spotted Fever: A Case Series from South India.

Purpura fulminans (PF) is associated with acute infections such as meningococcal, staphylococcal, streptococcal, and rickettsial infections. However, there are only a few reports of association of PF with rickettsial fever from India. In this case series of seven adults with PF, four were definitive cases of spotted fever as the ompA real-time polymerase chain reaction was positive. The other three adults were probable cases of spotted fever, as they were positive by immunoglobulin M enzyme-linked immunosorbent assay, and their fever subsided within 72 h of rickettsia-specific therapy. Three of the seven patients had peripheral gangrene. These patients, despite presenting with severe spotted fever, had a favorable outcome. This is attributed to the high index of suspicion and early treatment supported by diagnostic assays.

Clinical profile of hereditary angioedema from a tertiary care centre in India.

INTRODUCTION: Hereditary angioedema (HAE) is a clinical condition which could be fatal if not identified and managed appropriately. Knowledge of this condition is mostly confined to individual case reports and literature reviews in India. In this retrospective study we describe HAE cases which presented to a tertiary care centre in India over a period of three and half years. MATERIALS AND METHODS: Clinical case records of forty-two HAE patients diagnosed based on clinical and laboratory features were accessed after due approval from the Ethics committee. C1 esterase inhibitor (C1 INH) and C4 levels were measured using nephelometry. All relevant data was entered into Microsoft EXCEL worksheet and analysed using simple statistical tools. RESULTS: Among the 42 patients diagnosed as having HAE, 37 had low C1INH levels and were diagnosed to have type 1 HAE. The remaining 5 had normal C1 INH levels and were considered probable HAE based on family history and response to HAE specific treatment. The median age of onset of symptoms was 15 years (range 5-49) and median age at diagnosis, 27.5 years (range 5-55). The median delay in diagnosis was 10 years (range 1-27 years). Family history of HAE was observed in 52.6% and 29% reported deaths in the family with HAE like disease. Low dose androgens or tranexamic acid or both were prescribed in 64.2% of the patients. Orofacial edema was the commonest clinical presentation (76%) followed by edema of the extremities (38%), GI tract symptoms (19%) and genital involvement (11.9%). CONCLUSION: Many cases of HAE may be going undetected in India. There is a need for clinical awareness and laboratory means to accurately identify and administer appropriate treatment.

Assessment of two immunoassays for detection of IgM antibodies to scrub typhus using a serum panel.

Laboratory tests are necessary for diagnosis of scrub typhus (ST) especially in the absence of the distinctive eschar. Performance of an ELISA and ICT (immunochromatography) to detect IgM antibodies to scrub typhus was assessed using a panel of 346 sera chosen from healthy individuals, those with scrub typhus and scrub-typhus like illness. A sensitivity of 98.7% for ST IgM ICT and 97.4% for ST IgM ELISA was observed while specificity was 96.3% for ICT and 95.9% for ELISA. As excellent concordance (98.8%) was noted between the two assays, IgM ICT can be used for rapid diagnosis of scrub typhus. Abbreviations: ST IgM ELISA: Scrub typhus IgM ELISA; ST IgM ICT: Scrub Typhus IgM Immunochromatography, Rapid diagnostic test: RDT.

Eschar and IgM ELISA in the diagnosis of scrub typhus.

Scrub typhus is one of the leading causes of acute febrile illness in India. This study aimed to determine the best diagnostic tool for the identification of scrub typhus and study the possible association between diagnostics and clinical characteristics. Patients with fever of ≤15 days admitted to the hospital satisfying the case definition of 47 kDa quantitative polymerase chain reaction (qPCR) positivity OR scrub typhus IgM ELISA positivity along with the presence of eschar OR Scrub typhus IgM ELISA positivity along with defervescence of fever within 72 h of initiation of specific therapy were recruited. Of the 116 patients satisfying the case definition, 47 kDa qPCR was positive in 43 (37%) patients, whereas IgM ELISA was positive in 104 (90%) patients and eschar was seen in 59 (51%) patients. The median duration of fever was 7.5 days (interquartile range 6-10 days). Multiorgan dysfunction syndrome (MODS) was described in 44 (37.9%) patients. Two patients (1.8%) succumbed to the illness. Presence of eschar and IgM ELISA positivity were detected in 106 (91%) cases. Scrub typhus, even with MODS, has low mortality because of immediate institution of specific therapy due to physician awareness. The presence of eschar and IgM ELISA positivity can be used to detect a majority of cases of scrub typhus.

Septicemic listeriosis: An emerging food-borne illness in India?

Listeriosis is a food borne illness of significant public health concern, caused by consumption of food contaminated by gram negative bacilli, Listeria monocytogenes. Clinical listeriosis is relatively rare and it has varying spectrum of presentation, ranging from severe sepsis in immune-compromised individuals, febrile gastroenteritis and meningo-encephalitis in infants and adults. This disease is under reported in developing nations due to the lack of awareness and inadequate laboratory facilities to promptly isolate and identify the organism. We report a case of sporadic food-borne listeriosis, in an otherwise healthy individual presenting with meningo-encephalitis. Prompt identification and appropriate antibiotic therapy led to a favorable outcome.

Multi locus sequence typing of Burkholderia pseudomallei isolates from India unveils molecular diversity and confers regional association in Southeast Asia.

OBJECTIVES: Burkholderia pseudomallei, the causative agent for melioidosis, has become a public health problem in India and across the world. Melioidosis can be difficult to diagnose because of the inconsistent clinical presentations of the disease. This study aims to determine the genetic diversity among the clinical isolates of B. pseudomaelli from India in order to establish a molecular epidemiology and elucidate the Southeast Asian association. METHODS: Molecular typing using multi locus sequence typing was performed on thirty one archived B. pseudomallei clinical isolates, previously characterised from specimens obtained from patients admitted to the Christian Medical College & Hospital, Vellore from 2015 to 2016. Further investigations into the genetic heterogeneity and evolution at a regional and global level were performed using insilico tools. RESULTS: Multi locus sequence typing (MLST) of the isolates from systemic and localized forms of melioidosis, including blood, pus, tissue, and urine specimens, revealed twenty isolates with novel sequence types and eleven with previously reported sequence types. High genetic diversity was observed using MLST with a strong association within the Southeast Asian region. CONCLUSIONS: Molecular typing of B. pseudomallei clinical isolates using MLST revealed high genetic diversity and provided a baseline molecular epidemiology of the disease in India with a strong Southeast Asian association of the strains. Future studies should focus on whole genome based Single-Nucleotide-Polymorphism (SNP) which has the advantage of a high discriminatory power, to further understand the novel sequence types reported in this study.

Abiotrophia defectiva endarteritis with infective spondylodiscitis in an adult patient with patent ductus arteriosus.

Endarteritis is a major complication in patients with patent ductus arteriosus, causing significant morbidity and mortality. We report an adult patient with asymptomatic patent ductus arteriosus and endarteritis involving the main pulmonary artery and secondary infective spondylodiscitis at the L5-S1 intervertebral disc caused by Abiotrophia defectivaA. defectiva, commonly referred to as nutritionally variant streptococci, cannot be identified easily by conventional blood culture techniques from clinical specimens. Its isolation was confirmed by 16S ribosomal RNA sequencing. The patient was successfully managed with a combination of penicillin G and gentamicin, pending surgical repair of the patent ductus arteriosus.

Coexistence of Fosfomycin and Colistin Resistance in Klebsiella pneumoniae: Whole-Genome Shotgun Sequencing.

Resistance to colistin is a major threat that limits therapeutic choices for treating carbapenem-resistant Klebsiella pneumoniae infections. Herein, we report the draft genome sequences of two colistin-resistant K. pneumoniae isolates (BA41763 and B6753). The sequence data indicate that BA41763 and B6753 contain genomes of ~5.9 and 5.7 Mb in size with several plasmids.