Ravikar Ralph

The Twin Epidemics of Tuberculosis and HIV.

The deadly combination of tuberculosis (TB) and human immunodeficiency virus (HIV) currently ravaging the world, taking a toll of about 0.35 million people every year, is one of the major public health crises of the decade. Throughout the course of HIV infection, the risk of acquisition, reactivation, and reinfection of TB keeps increasing substantially as the immune deficiency progresses. TB coinfected patients inadvertently facilitate HIV infection by release of the proinflammatory cytokines and overexpression of coreceptors CXCR4 and CCR5; thereby, the progression of each is facilitated. The difficulties in diagnosing active tuberculosis in HIV-infected individuals poses a great challenge that is further complicated by the challenges in identification of latent TB infection, creating a setback to preventive therapy. Furthermore, prescribing antituberculous therapy and antiretroviral therapy together poses several management challenges, including drug interactions, added toxicities, and TB immune reconstitution inflammatory syndrome. The current approach to diagnosis, prevention, and treatment strategies in TB and HIV coinfected individuals, along with epidemiology and overview of pathogenetic interplay of both microbes, is reviewed here.

Diagnosis and management of Panton-Valentine leukocidin toxin associated Staphylococcus aureus infection: an update

The incidence of invasive Staphylococcus aureus (SA) infection has increased in the past decade and is associated with poor outcomes and high mortality rates. Of all the virulence factors, Panton-Valentine Leukocidin (PVL) has received the greatest attention. PVL producing SA strains are more likely to produce severe skin and soft tissue infections (SSTIs) and necrotizing pneumonia. This review focuses on the current evidence on PVL-SA virulence, epidemiology, clinical disease and treatment with relevance to healthcare in India.

Extrapyramidal effects of acute organophosphate poisoning.

Abstract Background: There is limited information on extrapyramidal symptoms in acute organophosphate (OP) poisoning. We describe the course and outcome of severely poisoned patients who develop extrapyramidal manifestations. Methods: In this prospective observational study, spanning 8 months (Apr–Nov 2013) adult patients (>18 years) admitted with OP poisoning were enrolled. Patients on anti-psychotic therapy, those refusing consent or presenting with co-ingestions were excluded. Treatment included atropine and supportive care (e.g. ventilation and inotropes as indicated); oximes were not administered. The presence of rigidity, tremors, dystonia and chorea were assessed daily till discharge using modifications of the Unified Parkinson’s Disease rating scale and the Tremor rating scale. The presence of extrapyramidal manifestations was correlated with length of ventilation and hospital stay and mortality. Results: Of the 77 patients admitted with OP poisoning, 32 were enrolled; 17 (53.1%) developed extrapyramidal manifestations which included rigidity (94.1%), tremors (58.8%) and dystonia (58.8%). None developed chorea. The median (inter-quartile range) time of symptom onset was 8 (5–11) days; extrapyramidal features resolved in 11 (6–17) days. The median duration of intensive care stay in patients not developing extrapyramidal symptoms was 6 (2–8) days, indicating that most of these patients had recovered even before symptom onset in patients who developed extrapyramidal manifestations. Overall, 27/32 (84%) were ventilated. Hospital mortality was 6.25% (2/32). When compared with patients not developing extrapyramidal signs, those with extrapyramidal manifestations had significantly prolonged ventilation (5 versus 16 median days; p = 0.001) and hospitalization (8 versus 21 days; p < 0.001), reduced ventilator-free days (23 versus 12 days; p = 0.023) and increased infections (p = 0.03). The need for ventilation and mortality were not significantly different (p > 0.6). Extrapyramidal symptoms were not observed in non-OP poisoned patients with prolonged ICU stay. Conclusion: In this small series of acute OP poisoning, extrapyramidal manifestations were common after 1 week of intensive care but self-limiting. They are significantly associated with longer duration of ventilation and hospital stay.

Carbapenem resistant Klebsiella pneumoniae isolated from bloodstream infection: Indian experience.

Abstract Increased incidence of multidrug resistant (MDR) Gram negative infection has resulted in high rates of morbidity and mortality. Klebsiella pneumoniae is one of the commonest MDR pathogens causing bacteraemia with limited therapeutic options such as colistin and tigecycline. Present study focused on molecular characterisation of MDR K. pneumoniae from bloodstream infection and their clinical outcome. A total of 115 K. pneumoniae from January 2015 to September 2016 were included in the study which comprised of phenotypically identified ESBL and carbapenem resistant (CR) isolates. Multiplex PCR was performed for detection of resistance genes encoding β-lactam resistance. This includes blaSHV, blaTEM, blaVEB, blaPER, blaCTX-M, blaDHA, blaCIT, blaFOX, blaACC, blaACT, blaNDM, blaOXA48-like, blaVIM and blaKPC. Co-expression of blaSHV, blaTEM and blaCTX-M was predominant with 64% (74/115) prevalence. CTX-M-1 was the variant produced by all the isolates producing CTX-M. AmpC was uncommon, seen in 5% of the isolates (6/115). Among the carbapenemases co-expression of blaNDM and blaOXA48-like was observed in 28% (32/115) and blaNDM in 19% (22/115) and blaOXA48-like in 13% (15/115). blaKPC was absent. Overall mortality was observed to be 57% (64/113) and mortality among CR K. pneumoniae (Kp) was 68% (50/73). The antibiotics that were administered for treatment of CRKp were colistin in 90% (66/73) and tigecycline in 7% (5/73) and in 99% combined with meropenem (72/73). Prevalence of community acquired and nosocomial infections were 5% (4/73) and 95% (69/73) respectively among CRKp. Minocycline and meropenem susceptibilities were comparable and hence minocycline can be a carbapenem sparing agent. The resistance to β-lactam antibiotics is steadily increasing and are plasmid mediated, their containment in healthcare setting is a challenge.

Antinuclear antibodies in scrub typhus: Transient occurrence during acute illness

Background & objectives: The pathological hallmark of scrub typhus infection is focal or disseminated vasculitis. As with other infections, antinuclear antibodies (ANA) have been previously described in scrub typhus. However, the underlying mechanisms and implications of this immunological phenomenon is not well understood. In the present work it was assessed whether ANA is associated with illness severity and outcomes. Methods: In this prospective study spanning one year, patients fulfilling the diagnostic criteria for scrub typhus were recruited. Patients with other acute infective febrile illnesses were taken as controls. ANA positivity was compared between the cases and controls. ANA in scrub typhus was assessed for correlation with disease severity, organ dysfunction and outcomes. Results: The cohort comprised of 149 patients (scrub 89; controls 60) with mean age 46.5 (SD=16.9) yr; 48.3% were female. ANA was detected in 48 (53.9%) patients with scrub typhus and 9(15%) controls (p < 0.001). The ANA pattern was predominantly speckled (93.8%) in both scrub typhus patients and controls. In patients with scrub typhus, ANA positivity was associated with increasing APACHE-III score [Odds ratio (OR) 1.01; 95% CI 0.99–1.03; p = 0.09]. On bivariate analysis, ANA tended to be correlated with acute respiratory distress syndrome (OR 2.32; 95% CI 0.98–5.46; p = 0.06), hepatic dysfunction (OR 2.25; 95% CI 0.94–5.39, p = 0.06) and aseptic meningitis (OR 6.83; 95% CI 0.80–58.05, p = 0.08). The presence of these antibodies did not correlate with duration of hospitalization or mortality. Convalescent sera on 31 ANA positive scrub typhus patients demonstrated persistence of ANA in only 5 (16.1%) patients. Interpretation & conclusion: The disappearance of ANA during the convalescent phase suggests that ANA is expressed during the acute phase of scrub typhus infection. Its association with organ dysfunction warrants further study of the mechanisms and impact of autoantibody formation in scrub typhus.

Invasive pneumococcal disease in Indian adults: 11 years' experience

PURPOSE To investigate the epidemiology of invasive pneumococcal disease (IPD), prevalent serotypes, and pattern of antimicrobial resistance (AMR) in Indian adults. METHODS Prospective laboratory based surveillance of IPD was carried out in >18 years age group between January 2007 and July 2017, from a tertiary care hospital in South India. All Streptococcus pneumoniae culture positives from blood, CSF and sterile body fluids were characterized to identify the serotypes and AMR. RESULTS A total of 408 IPD cases were characterized in this study. The overall case fatality rate in this study was 17.8% (95% confidence interval (CI): 14.1, 22.4). Pneumonia (39%), meningitis (24.3%), and septicaemia (18.4%) were the most common clinical conditions associated with IPD. Serotypes 1, 3, 5, 19F, 8, 14, 23F, 4, 19A and 6B were the predominant serotypes in this study. Penicillin non-susceptibility was low with 6.4% CONCLUSION: Serotype data from this study helped in accurate estimation of pneumococcal conjugate vaccine-13 and pneumococcal polysaccharide vaccine-23 protective coverage against serotypes causing IPD in India as 58.7% (95% CI: 53.8, 63.4) and 67.4% (95% CI: 62.7, 71.8) respectively. Penicillin non-susceptibility in meningeal IPD cases is 27.4%. Empirical therapy for meningeal IPD must be cephalosporin in combination with vancomycin since cefotaxime non-susceptibility in meningeal IPD is 9.9.

Typhoid fever: issues in laboratory detection, treatment options & concerns in management in developing countries

Multidrug-resistant Salmonella enterica subsp. enterica serovar Typhi (resistant to ampicillin, chloramphenicol and cotrimoxazole), was significantly reduced with the increased usage of fluoroquinolones and azithromycin. This has led to declining multidrug resistance rates in India with increasing ciprofloxacin nonsusceptibility rates and clinical failures due to azithromycin. However, for the available agents such as ceftriaxone, azithromycin and fluoroquinolones, the dose and duration for treatment is undefined. The ongoing clinical trials for typhoid management are expected to recommend the defined dose and duration for better clinical outcome. We made an attempt to summarize the issues in laboratory detection, treatment options and responses, and the concerns in clinical practice seen in the developing countries.

Citrobacter freundii : A rare cause of native valve endocarditis

Citrobacter species are usually intestinal tract colonizers and occasionally cause nosocomial infections such as urinary tract, respiratory tract, and wound infections. However, native valve endocarditis due to these organisms is extremely rare. We report a human immunodeficiency virus-infected individual with Citrobacter freundii endocarditis of the native aortic valve.