Laboratory markers predictive of fulminant Clostridioides difficile infection refractory to fluid resuscitation.

BACKGROUND: Old age, leucocytosis, hypoalbuminemia, and elevated creatinine have been identified as risk factors for fulminant Clostridioides difficile infection (CDI). High ATLAS scores have also been linked to fatal disease. The affiliated studies, however, involved patients prescribed metronidazole - a regimen no longer standard of care. The variables were thus reassessed in patients prescribed optimal therapy. METHODS: Adults hospitalized with CDI at University of Kentucky Medical Center were retrospectively reviewed. Enrolled subjects were separated according to disease classification i.e. non-severe/severe versus fulminant CDI. Fulminant patients were further subdivided into hypotensive persons responsive to fluid resuscitation, and those with sequent shock, ileus, or megacolon. Following partition, the cohorts underwent correlation analysis. FINDINGS: Forty-five subjects had non-severe/severe disease. Thirteen fulminant CDI patients responded to fluid resuscitation. Seventeen fulminant CDI patients developed shock, ileus, or megacolon. Median WBC counts, albumin values, and ATLAS scores varied among the cohorts. Although WBC counts were similar among the fulminant subsets, declining albumin values and increasing ATLAS scores mirrored disease worsening. Logistic regression revealed albumin values < 20 g/L (odds ratio [OR] 3.91) and ATLAS scores ≥ 6 (OR 5.03) to predict critical illness in hypotensive persons. CONCLUSION: Median WBC counts, albumin values, and ATLAS scores differed in patients separated by CDI severity. A notable variance in albumin values and ATLAS scores between fluid responsive fulminant disease and critical illness was moreover seen. The finding suggests hypoalbuminemia and high ATLAS scores in hypotensive CDI patients may herald shock, ileus, or megacolon.

Prevalence and genetic analysis of phenotypically Vi- negative Salmonella typhi isolates in children from Kathmandu, Nepal.

The Vi capsular polysaccharide (ViPS) protects Salmonella enterica subspecies enterica serotype Typhi (S.Typhi) in vivo by multiple mechanisms. Recent microbiological reports from typhoid endemic countries suggest that acapsulate S.Typhi may occur in nature and contribute to clinical typhoid fever that is indistinguishable from disease caused by capsulate strains. The prevalence and genetic basis of ViPS-negative S.Typhi isolates in children from Kathmandu, Nepal, were tested in 68 isolates. Although 5.9% of isolates tested negative for capsular expression by slide agglutination tests, a novel multiplex PCR assay and individual PCR analyses demonstrated the presence of all 14 genes responsible for the synthesis, transportation and regulation of the ViPS. These data suggest that phenotypically acapsulate S.Typhi may not have a genetic basis for the same.

Role of procalcitonin in guiding antibiotic therapy.

PURPOSE: The role of procalcitonin in guiding antibiotic therapy is reviewed. SUMMARY: Procalcitonin is a prohormone for calcitonin, which is secreted by the parafollicular cells of the thyroid gland. The biological activity of procalcitonin is significantly different from calcitonin and is believed to be part of the complex inflammatory cascade of the immune system. Procalcitonin has been shown to be elevated in bacterial infections but not in viral infections or other inflammatory conditions. The first published study that suggested that procalcitonin levels increased in the presence of bacterial infection was conducted in France in the early 1990s. Numerous studies have been conducted using procalcitonin-guided therapy to reduce antibiotic use. These studies were performed in one of three clinical settings: outpatient primary care (two multicenter, noninferiority studies of patients with upper- and lower-respiratory-tract infections), emergency room and inpatient (five studies in patients with chronic obstructive pulmonary disease, exacerbation, bronchitis, or community-acquired pneumonia), and the intensive care unit (ICU) (two studies in medical ICU patients and two in postoperative ICU patients with infection or sepsis). Based on the findings of these studies, a cutoff value of 0.25 µg/L in non-ICU patients or of 0.5 µg/L in ICU patients seems appropriate for making a decision about the initiation and discontinuation of antibiotic therapy. In patients with a significantly elevated baseline procalcitonin level, a subsequent drop of >80% appears to be reasonable for discontinuing antibiotics. CONCLUSION: Published evidence supports the use of procalcitonin as a biomarker of bacterial infection that can be used to reduce antibiotic exposure.

The burden of vaccine-preventable invasive bacterial infections and pneumonia in children admitted to hospital in urban Nepal.

BACKGROUND: Protein-polysaccharide vaccines have made a significant impact on the burden of disease caused by encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and have the potential to do so for Salmonella Typhi. Nepal is one of many resource-poor nations with limited information on the epidemiology of childhood infections caused by these pathogens. METHODS: Over a 21-month period, we studied children aged ≤12 years admitted to an urban hospital in Nepal with suspected bacteremia, meningitis, or pneumonia. Patan Hospital is a non-profit hospital with the second largest pediatric unit in the Kathmandu Valley. RESULTS: Of 2039 children enrolled in the study, 142 (7.5%) included in the analysis had positive blood cultures. The agents of enteric fever, Salmonella Typhi and Salmonella Paratyphi, accounted for 59/142 (42%) of all bacteremias and were the most frequently cultured pathogens in children ≥1 year of age. S. pneumoniae was isolated in 16% of positive blood cultures and was the most common cause of bacteremia in children <1 year of age. Pneumonia accounted for 51% of admissions in children ≥2 months, with 44% of these children having radiographically defined primary endpoint pneumonia. S. pneumoniae was the most commonly identified pathogen in cases of pneumonia and meningitis. The S. pneumoniae serotype distribution indicated that the 10-valent and 13-valent pneumococcal conjugate vaccines would cover 44% and 47%, respectively, of all S. pneumoniae cultured from blood or cerebrospinal fluid (CSF) isolates and 62% and 67%, respectively, of isolates associated with pneumonia. H. influenzae type b was isolated infrequently from blood or CSF cultures, but is likely to be more important as a cause of pneumonia. CONCLUSIONS: The data on the burden of invasive bacterial infections and pneumonia from this study suggest that vaccines in development against Salmonella Typhi and the pneumococcus have the potential to significantly improve the health of children in Nepal.

Hospital-based surveillance of invasive pneumococcal disease among young children in urban Nepal.

BACKGROUND: Streptococcus pneumoniae is a leading cause of pneumonia and meningitis in young children. Before implementation of the pneumococcal conjugate vaccine in developing countries, there is an urgent need to provide regional epidemiological data on pneumococcal disease. The aims of this study were to determine the prevalence and serotype distribution of invasive pneumococcal disease among young children hospitalized in urban Nepal. METHODS: Children aged 2 months to 5 years who were admitted to Patan Hospital, Kathmandu, with fever and/or suspected pneumonia, meningitis, or bacteremia were recruited. Blood culture specimens were collected from all participants. In cases of suspected meningitis, cerebrospinal fluid specimens were cultured and were tested for S. pneumoniae antigen. RESULTS: A total of 885 children were recruited during the 21-month study period. Of these, 76 (9%) had meningitis and 498 (56%) had pneumonia, on the basis of clinical criteria. Radiographically confirmed pneumonia occurred in 354 (40%), and probable or definite meningitis occurred in 47 (5%). S. pneumoniae was isolated in specimens from 17 (2%) of the children. Serotypes 1 and 12A were isolated most frequently, and only 1 of 17 isolates had a serotype contained in the currently available 7-valent pneumococcal conjugate vaccine. CONCLUSIONS: More than 60% of children aged <5 years who were admitted with fever and/or suspected invasive bacterial disease in urban Nepal had the clinical syndromes of meningitis and/or pneumonia. A new generation of pneumococcal vaccines that prevent infection with a broader range of serotypes may be necessary to most effectively control pneumococcal disease in young children in Kathmandu.