Sudha Jasmine

Invasive pneumococcal disease associated with high case fatality in India

OBJECTIVE To study the seroepidemiology and antimicrobial resistance pattern of invasive pneumococcal disease (IPD) in older subjects who are admitted to hospitals in India. STUDY DESIGN AND SETTING Prospective surveillance of IPD in patients older than 18 years in seven large academic teaching hospitals in India from 1993 to 2008. All subjects who had Streptococcus pneumoniae isolated from normally sterile body fluids or were antigen positive in cerebrospinal fluid, ascitic fluid, and pleural fluid were identified as IPD cases in the study. Serotype/group (STG) and minimum inhibitory concentration for penicillin, chloramphenicol, co-trimoxazole (trimethoprim-sulfamethoxazole), erythromycin, and cefotaxime were determined. RESULTS A total of 1,037 adult subjects with suspected invasive bacterial infection were recruited in the study. S pneumoniae was identified from normally sterile body fluids in 449 (43.3%) subjects. Meningitis (34.3%) and pneumonia (33.9%) were the most common clinical conditions associated with IPD. The case fatality was 25-30% across all age groups. Penicillin resistance was low at 2.7% overall. Resistance to co-trimoxazole was noted to be high and increasing in the study period from 42.9% in 1993 to 85.2% in 2008 (P = 0.001). The most common STG was serotype 1, which accounted for 22.9% of all isolates. The 23-valent pneumococcal polysaccharide vaccine covered 83.3% of the STGs (49/54; 95% confidence interval: 79.7, 96.9) for patients older than 60 years. CONCLUSION IPD continues to be a problem in India and is associated with high case fatality in spite of treatment in the hospital setting. Penicillin resistance is currently low in India. More than 80% of invasive STGs causing disease in the elderly in India are included in the formulation of polysaccharide pneumococcal vaccine.

A clinical study of renal tubular dysfunction in Cleistanthus collinus (Oduvanthalai) poisoning

Introduction. Self-poisoning through the ingestion of Oduvanthalai is common in South India. Mortality may occur because of arrhythmias, renal failure, shock, and respiratory distress. The mechanisms of toxicity are unclear. This prospective, clinical study was designed to assess renal tubular dysfunction because of Oduvanthalai poisoning. Methods. Thirty-two consecutive patients admitted with Oduvanthalai poisoning at a tertiary care hospital in South India, from June 2007 to August 2009 (26 months), were evaluated through history, physical examination, and laboratory studies. Following an interim analysis, additional studies of renal tubular function were performed on a subcohort of eight patients. These included the following: (1) urinary pH, daily serum, and urine anion gap; (2) 24-h urine protein and potassium; and (3) assessment of urine hexosaminidase and amino acid levels. Results. Metabolic acidosis (100%), which persisted at discharge (65.6%), hypokalemia (62.5%), and renal failure (15.6%), was apparent in the total cohort. Tests of renal tubular function on the subcohort revealed a normal anion gap, hyperchloremic, metabolic acidosis of renal etiology, defective urinary acidification, and hypokalemia with kaliuresis, indicative of distal renal tubular acidosis in six patients. Urinary hexosaminidase and amino acid levels, markers of proximal tubular dysfunction, were elevated in seven and two patients, respectively. Conclusions. Distal renal tubular acidosis is an important feature of Oduvanthalai poisoning. Proximal tubular injury and, in more severe forms, global tubular dysfunction with diminished glomerular filtration rate may occur.

Performance of clinical scoring systems in acute organophosphate poisoning

Abstract Introduction. Clinical scoring systems are used to predict mortality rate in hospitalized patients. Their utility in organophosphate (OP) poisoning has not been well studied. Methods. In this retrospective study of 396 patients, we evaluated the performance of the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the Simplified Acute Physiology Score (SAPS) II, Mortality Prediction Model (MPM) II, and the Poisoning Severity Score (PSS). Demographic, laboratory, and survival data were recorded. Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC) was calculated to study the relationship between individual scores and mortality rate. Results. The mean (standard deviation) age of the patients was 31.4 (12.7) years, and at admission, their pseudocholinesterase (median, interquartile) level was 317 (222–635) U/L. Mechanical ventilation was required in 65.7% of the patients and the overall mortality rate was 13.1%. The mean (95% confidence interval) scores were as follows: APACHE-II score, 16.4 (15.5–17.3); SAPS-II, 34.4 (32.5–36.2); MPM-II score, 28.6 (25.7–31.5); and PSS, 2.4 (2.3–2.5). Overall, the AUC for mortality was significantly higher for APACHE-II (0.77) and SAPS-II (0.77) than the PSS (0.67). When patients were categorized, the AUCs were better for WHO Class II (0.71–0.82) than that for Class I compounds (0.60–0.66). For individual compounds, the AUC for APACHE-II was highest in quinalphos (0.93, n = 46) and chlorpyrifos (0.86, n = 38) and lowest in monocrotophos (0.60, n = 63). AUCs for SAPS-II and MPM-II were marginally but not significantly lower than those for APACHE-II. The PSS was generally a poorer discriminator compared to the other scoring systems across all categories. Conclusions. In acute OP poisoning, the generic scoring systems APACHE-II and SAPS-II outperform the PSS. These tools may be used to predict the mortality rate in OP poisoning.

Organophosphate-pyrethroid combination pesticides may be associated with increased toxicity in human poisoning compared to either pesticide alone

Abstract Background. Organophosphate (OP) poisoning results in significant toxicity while pyrethroid poisoning is associated with extremely low fatality. OPs can inhibit the detoxification of pyrethroid and increase the toxicity of the combination. We assessed whether mixed OP-pyrethroid poisoning impacted outcome in human poisoning. Methods. Patients were identified from a prospectively collected institutional poisoning database that incorporates demographic and outcome data of patients presenting with poisoning. Results. Of the 1177 poisoned patients admitted over 2 years, 32 presented with OP-pyrethroid (50% chlorpyrifos-5% cypermethrin mixture) poisoning (Group 1), 26 consumed 20% chlorpyrifos (Group 2), and 32 took 15% cypermethrin (Group 3). Seizures occurred in 15.6% (n = 5) with chlorpyrifos-cypermethrin poisoning, 18.8% (n = 6) with cypermethrin poisoning, and 3.9% (n = 1) with chlorpyrifos poisoning. Ventilatory requirements were 53.5% (17/32), 42.3% (11/26), and 15.7% (5/32) in Groups 1–3, respectively. Ventilator-free days (Mean ± SD) was significantly lower (p < 0.006) in Group 1 (20.9 ± 9.3 days) than those in Group 2 (26.1 ± 4.4 days) or 3 (27.8 ± 0.6). The median (inter-quartile range) hospital stay was 5.5 (4–19.5), 5 (5–6), and 1 (0.65–1.5) days, respectively, in the three groups. Four patients died in Group 1 (13%). None died in the other groups. Conclusion. Although confounded by the varying quantity of chlorpyrifos and cypermethrin in the different formulations, patients with mixed poisoning appear to have shorter ventilator-free days than patients poisoned by either of the pesticides alone. Further studies are required comparing patients poisoned by formulations with similar quantities of OP and pyrethroid or with analysis of blood pesticide concentration on admission.

Scrub typhus meningitis: An under-recognized cause of aseptic meningitis in India

BACKGROUND Central nervous system (CNS) involvement in scrub typhus is seen in up to a quarter of patients. However, the literature on cerebrospinal fluid (CSF) analysis and outcome in meningitis/meningo-encephalitis due to scrub typhus is scant. MATERIALS AND METHODS This retrospective study included patients who were admitted to a medical college hospital with scrub typhus meningitis/meningo-encephalitis between 2005 and 2011. The clinical and laboratory profile, details of CSF analysis and outcome were documented. RESULTS The study included 189 patients with meningitis/meningo-encephalitis due to scrub typhus. The mean age of the patients was 41 ± 4 years. The mean duration of fever before presentation was 9.4 ± 3 days. The common presenting complaints were headache (64.2%), nausea/vomiting (60%), altered sensorium (53.7%) and seizures (22.1%). The presence of an eschar was documented in 27.5% of the patients. The mean CSF white blood count was 80 cells/cu mm (range: 5-740). There was a clear lymphocyte predominance (mean 87.6%). The mean CSF protein level was 105 mg% (range: 13-640). The mean CSF sugar level was 63.9 mg% (range 25-350), and was less than 40 mg% in 11.1% of the cases. The case fatality rate was 5.8% (11/189). Univariate analysis showed the presence of an eschar (15.4% vs 2.2%; Odds Ratio [OR]: 8.1) and altered sensorium (9.8% vs 1.1%; OR: 9.2) to be significant predictors of mortality. CONCLUSIONS In endemic regions, scrub typhus should be considered in the differential diagnosis of aseptic meningitis. Modest elevation of cells in the CSF with lymphocytic pleocytosis and multi-organ involvement may indicate scrub typhus meningitis/meningo-encephalitis.

Clinical spectrum of yellow phosphorous poisoning in a tertiary care centre in South India: a case series.

Rodenticides such as yellow phosphorus are highly toxic compounds which are commonly used for pest control. Reports of yellow phosphorus poisoning from tropical nations is scanty. In this retrospective study, we report the clinical features, mortality and predictors of mortality among nine patients at a tertiary care centre in south India. Yellow phosphorus consumption was common among a younger age group of patients. The mean duration of presentation after consumption was five days. The most common clinical manifestations seen were abdominal pain and vomiting followed by a depressed sensorium. Features of acute liver failure including coagulopathy were seen in all patients. Despite all patients receiving supportive therapy, a poor outcome or death resulted in the majority. Early referral to a tertiary care centre, meticulous monitoring and supportive measures are key elements of patient management as there are no specific antidotes available at present. Increase in public and physician awareness to the toxin and implementation of preventive policies is of utmost importance.

Prevalence of toxin genes among the clinical isolates of Staphylococcus aureus and its clinical impact

Introduction: Staphylococcus aureus (S. aureus) causes a variety of infections, ranging from a mild skin infection to blood stream infections and deep seated infections. As Stapylococcus aureus bacteremia (SAB) has the tendency to cause endovascular and metastatic infections, complications can occur at almost all sites of the body. Hence, SAB is associated with increased morbidity and mortality in spite of appropriate antimicrobial treatment. The virulence in S. aureus is determined by the presence of adhesins and toxins, which behave like superantigens (SAgs) and leads to a massive release of proinflammatory cytokines causing overwhelming inflammatory response leading to endothelial leakage, hemodynamic shock, multiorgan failure, and possibly death. Materials and Methods: One year prospective study conducted in a tertiary care hospital in southern part of India included all patients with SAB. Clinical details were filled according to. All isolates were subjected to polymerase chain reaction (PCR) for enterotoxin profiling. Results: A total of 101 patients of SAB were identified which comprises of 61 (60.4%) patients with methicillin-susceptible S. aureus (MSSA) and 40 (39.6%) patients with methicillin-resistant S. aureus (MRSA). Most common predictors of mortality were prior hospitalization and antibiotic intake, severe organ dysfunction, shock, tachycardia, and leukocytosis. Two-third of the isolates had at least one enterotoxin, most prevalent was sea; 28% and 27% (P - value = 0.001) MSSA isolates had seg and sei; whereas, 38.6% (P - value < 0.001) of MRSA isolates were found to have sea. The most common enterotoxin associated with mortality was sei, which comprised of 38% of all mortality. Conclusion: In SAB, the significant predictors of mortality were prior hospitalization and antibiotic intake, presence of multiorgan dysfunction, and shock. Although overall significance between the enterotoxin and shock could not be demonstrated, it successfully demonstrated the difference of enterotoxin between MSSA and MRSA.

Effectiveness of treatment regimens for Typhoid fever in the nalidixic acid-resistant S. typhi (NARST) era in South India

The epidemiology of typhoid fever in South Asia has changed. Multi-drug resistant (MDR) Salmonella typhi (S. typhi) is now frequently resistant to nalidixic acid and thus labelled NARST. Treatment failure with the use of fluoroquinolones has been widely noted, forcing clinicians to adopt alternative treatment strategies. In this observational study, we looked at various treatment regimens and correlated clinical and microbiological outcomes. In 146 hospitalised adults, the median minimum inhibitory concentration (MIC) for ciprofloxacin was 0.38 µg/mL with a median fever clearance time (FCT) of eight days (range = 2–35 days). Of the regimens used, gatifloxacin and azithromycin had a shorter FCT of six days compared to ceftriaxone (ten days; P < 0.001). Though mortality and relapse in our cohort was low, NARST seemed to correlate with mortality (P = 0.006). Gatifloxacin or azithromycin clearly emerge as the drugs of choice for treatment of typhoid in South India.

Mycobacterial blood culture as the only means of diagnosis of disseminated tuberculosis in advanced HIV infection

The diagnosis of disseminated tuberculosis (TB) in advanced HIV infection is often delayed because of difficulty in obtaining suitable specimens for culture. A total of 32 such patients from South India with positive mycobacterial blood cultures were studied over ten years. Almost all (90%) had a febrile illness and the majority (68.7%) had clinical lung involvement, but only 27.3% had positive sputum smears. Liver biopsy yielded a positive diagnosis in only 1/7. Cytopenia was almost universal (96.9%). Bone marrow cultures were, however, positive in 54.8%, of whom one-quarter grew atypical mycobacteria. Mycobacterial blood culture is therefore a useful adjunct test to diagnose TB in advanced HIV.