Conventional vs Short Duration of Antibiotics in Patients With Moderate or Severe Cholangitis: Noninferiority Randomized Trial.

INTRODUCTION: Successful biliary drainage and antibiotics are the mainstays of therapy in management of patients with acute cholangitis. However, the duration of antibiotic therapy after successful biliary drainage has not been prospectively evaluated. We conducted a single-center, randomized, noninferiority trial to compare short duration of antibiotic therapy with conventional duration of antibiotic therapy in patients with moderate or severe cholangitis. METHODS: Consecutive patients were screened for the inclusion criteria and randomized into either conventional duration (CD) group (8 days) or short duration (SD) group (4 days) of antibiotic therapy. The primary outcome was clinical cure (absence of recurrence of cholangitis at day 30 and >50% reduction of bilirubin at day 15). Secondary outcomes were total days of antibiotic therapy and hospitalization within 30 days, antibiotic-related adverse events, and all-cause mortality at day 30. RESULTS: The study included 120 patients (the mean age was 55.85 ± 13.52 years, and 50% were male patients). Of them, 51.7% patients had malignant etiology and 76.7% patients had moderate cholangitis. Clinical cure was seen in 79.66% (95% confidence interval, 67.58%-88.12%) patients in the CD group and 77.97% (95% confidence interval, 65.74%-86.78%) patients in the SD group ( P = 0.822). On multivariate analysis, malignant etiology and hypotension at presentation were associated with lower clinical cure. Total duration of antibiotics required postintervention was lower in the SD group (8.58 ± 1.92 and 4.75 ± 2.32 days; P < 0.001). Duration of hospitalization and mortality were similar in both the groups. DISCUSSION: Short duration of antibiotics is noninferior to conventional duration in patients with moderate-to-severe cholangitis in terms of clinical cure, recurrence of cholangitis, and overall mortality.

Genomic features, antimicrobial susceptibility, and epidemiological insights into Burkholderia cenocepacia clonal complex 31 isolates from bloodstream infections in India.

Introduction: Burkholderia cepacia complex (Bcc) clonal complex (CC) 31, the predominant lineage causing devastating outbreaks globally, has been a growing concern of infections in non-cystic fibrosis (NCF) patients in India. B. cenocepacia is very challenging to treat owing to its virulence determinants and antibiotic resistance. Improving the management of these infections requires a better knowledge of their resistance patterns and mechanisms. Methods: Whole-genome sequences of 35 CC31 isolates obtained from patient samples, were analyzed against available 210 CC31 genomes in the NCBI database to glean details of resistance, virulence, mobile elements, and phylogenetic markers to study genomic diversity and evolution of CC31 lineage in India. Results: Genomic analysis revealed that 35 isolates belonging to CC31 were categorized into 11 sequence types (ST), of which five STs were reported exclusively from India. Phylogenetic analysis classified 245 CC31 isolates into eight distinct clades (I-VIII) and unveiled that NCF isolates are evolving independently from the global cystic fibrosis (CF) isolates forming a distinct clade. The detection rate of seven classes of antibiotic-related genes in 35 isolates was 35 (100%) for tetracyclines, aminoglycosides, and fluoroquinolones; 26 (74.2%) for sulphonamides and phenicols; 7 (20%) for beta-lactamases; and 1 (2.8%) for trimethoprim resistance genes. Additionally, 3 (8.5%) NCF isolates were resistant to disinfecting agents and antiseptics. Antimicrobial susceptibility testing revealed that majority of NCF isolates were resistant to chloramphenicol (77%) and levofloxacin (34%). NCF isolates have a comparable number of virulence genes to CF isolates. A well-studied pathogenicity island of B. cenocepacia, GI11 is present in ST628 and ST709 isolates from the Indian Bcc population. In contrast, genomic island GI15 (highly similar to the island found in B. pseudomallei strain EY1) is exclusively reported in ST839 and ST824 isolates from two different locations in India. Horizontal acquisition of lytic phage ST79 of pathogenic B. pseudomallei is demonstrated in ST628 isolates Bcc1463, Bcc29163, and BccR4654 amongst CC31 lineage. Discussion: The study reveals a high diversity of CC31 lineages among B. cenocepacia isolates from India. The extensive information from this study will facilitate the development of rapid diagnostic and novel therapeutic approaches to manage B. cenocepacia infections.

ROLE OF CHANGE IN THE LEVELS OF INFLAMMATORY MARKERS POST DRAINAGE IN PREDICTING OUTCOME IN ACUTE CHOLANGITIS.

BACKGROUND: Acute cholangitis (AC) is a gastro-intestinal emergency associated with significant mortality. Role of change in the levels of inflammatory markers post drainage in predicting outcome in acute cholangitis is uncertain. OBJECTIVE: To evaluate the predictive value of changes in C-reactive protein (CRP) and procalcitonin levels after biliary drainage in relation to outcomes (survival or mortality) at 1 month. METHODS: A prospective observational study of consecutive adults presenting with AC was performed. At admission and at 48 hours post biliary drainage, procalcitonin and CRP were sent. RESULTS: Between August 2020 till December 2020 we recruited 72 consecutive patients of AC. The median age of the patients was 55 years (range 43-62 years) and 42 (58.33%) were females. Although the delta change in serum procalcitonin (P value<0.001) and CRP (P value<0.001) was significant, it had no bearing on the outcome. Altered sensorium and INR were independently associated with mortality at 1 month. The 30-day mortality prediction of day 0 procalcitonin was measured by receiver operating characteristic analysis which resulted in an area under the curve of 0.697 with a 95% confidence interval (95%CI) of 0.545-0.849. The optimal cut-off of procalcitonin would be 0.57ng/mL with a sensitivity and specificity of 80% and 60% respectively to predict mortality. CONCLUSION: Change in serum procalcitonin and CRP levels at 48 hours post drainage although significant, had no impact on the outcome of acute cholangitis.

Papel da mudança nos níveis de marcadores inflamatórios pós drenagem na previsão de resultado em colangite aguda / Role of change in the levels of inflammatory markers post drainage in predicting outcome in acute cholangitis

ABSTRACT Background: Acute cholangitis (AC) is a gastro-intestinal emergency associated with significant mortality. Role of change in the levels of inflammatory markers post drainage in predicting outcome in acute cholangitis is uncertain. Objective: To evaluate the predictive value of changes in C-reactive protein (CRP) and procalcitonin levels after biliary drainage in relation to outcomes (survival or mortality) at 1 month. Methods A prospective observational study of consecutive adults presenting with AC was performed. At admission and at 48 hours post biliary drainage, procalcitonin and CRP were sent. Results: Between August 2020 till December 2020 we recruited 72 consecutive patients of AC. The median age of the patients was 55 years (range 43-62 years) and 42 (58.33%) were females. Although the delta change in serum procalcitonin (P value<0.001) and CRP (P value<0.001) was significant, it had no bearing on the outcome. Altered sensorium and INR were independently associated with mortality at 1 month. The 30-day mortality prediction of day 0 procalcitonin was measured by receiver operating characteristic analysis which resulted in an area under the curve of 0.697 with a 95% confidence interval (95%CI) of 0.545-0.849. The optimal cut-off of procalcitonin would be 0.57ng/mL with a sensitivity and specificity of 80% and 60% respectively to predict mortality. Conclusion: Change in serum procalcitonin and CRP levels at 48 hours post drainage although significant, had no impact on the outcome of acute cholangitis.

RESUMO Contexto: A colangite aguda (CA) é uma emergência gastro-intestinal associada à significativa mortalidade. O papel da mudança nos níveis de marcadores inflamatórios pós drenagem na previsão do desfecho em CA é incerto. Objetivo: Avaliar o valor preditivo das alterações nos níveis de proteína reativa C (PCR) e procalcitonina após drenagem biliar em relação aos desfechos (sobrevida ou mortalidade) em um mês. Métodos Realizou-se estudo observacional prospectivo de adultos consecutivos que apresentam CA. Na admissão e após 48 horas de drenagem biliar, foram analisadas a procalcitonina e a PCR. Resultados Entre agosto de 2020 e dezembro de 2020, foram recrutados 72 pacientes consecutivos de CA. A idade mediana dos pacientes foi de 55 anos (faixa de 43 a 62 anos) e 42 (58,33%) do sexo feminino. Embora a variação delta no soro procalcitonina (valor P<0,001) e PCR (valor P<0,001) tenha sido significativa, não houve influência sobre o resultado. Sensório alterado e INR foram independentemente associados à mortalidade em 1 mês. A previsão de mortalidade de 30 dias no dia 0 da procalcitonina foi medida pela análise característica operacional receptora que resultou em uma área sob a curva de 0,697 com intervalo de confiança de 95% (IC95%) de 0,545-0,849. O corte ideal de procalcitonina seria de 0,57ng/mL com sensibilidade e especificidade de 80% e 60% respectivamente para prever a mortalidade. Conclusão: A mudança nos níveis de procalcitonina sérica e PCR em 48 horas após a drenagem, embora significativa, não teve impacto no resultado da colangite aguda.

Biofilm inhibitory effect of alginate lyases on mucoid P. aeruginosa from a cystic fibrosis patient.

Chronic mucoid Pseudomonas aeruginosa infections are a major scourge in cystic fibrosis patients. Mucoid P. aeruginosa displays structured alginate-rich biofilms that are resistant to antibiotics. Here, we have assessed the efficacy of a panel of alginate lyases in combating mucoid P. aeruginosa biofilms in cystic fibrosis. Albeit we could not demonstrate alginate degradation by alginate lyases in sputum, we demonstrate that the endotypic alginate lyases, CaAly (from Cellulophaga algicola) and VspAlyVI (from Vibrio sp. QY101) and the exotypic alginate lyases, FspAlyFRB (from Falsirhodobacterium sp. alg1), and SA1-IV (from Sphingomonas sp. A1), indeed inhibit biofilm formation by a mucoid P. aeruginosa strain isolated from the sputum of a cystic fibrosis patient with comparative effect to that of the glycoside hydrolase PslG, a promising candidate for biofilm treatment. We believe that these enzymes should be explored for in vivo efficacy in future studies.

Outcome of percutaneous drainage in patients with pancreatic necrosis having organ failure.

BACKGROUND: Percutaneous catheter drainage (PCD) is an effective way of drainage in acute pancreatitis (AP) and its role in persistent organ failure (OF) has not been studied. This study assessed the outcome of severe AP managed with PCD. METHODS: We retrospectively analysed outcome of AP patients undergoing PCD for persistent OF with respect to success of PCD, etiology, severity scores, OF, imaging features and PCD parameters. Success of PCD was defined as resolution of with PCD and survived without surgical necrosectomy. RESULTS: Between January 2016 and May 2018, 83 patients underwent PCD for persistent OF at a mean duration of 25.59 ± 21.2 days from pain onset with successful outcome in 47 (56.6%) patients. Among PCD failures, eleven (13.25%) patients underwent surgery. Overall mortality was 31 (37.3%). On multivariate analysis, pancreatic necrosis <50% and absence of extrapancreatic infection (EPI) predicted the success of PCD. Presence of infected necrosis did not affect the outcome of PCD in organ failure. CONCLUSION: PCD improves the outcome in patients with OF even when done early irrespective of the status of infection of necrosis. Therefore, PCD may be considered early in the course of patients with OF.

Review of a 7-year record of the bacteriological profile of airway secretions of children with cystic fibrosis in North India.

Background: Cystic fibrosis (CF) is now a recognised entity in India, with prevalence rates between 1/10,000 and 1/50,000. However, no data were available with regard to the profile of respiratory pathogens in the Indian setting. Materials and Methods: The records of respiratory secretion bacterial cultures of children with CF in a tertiary care hospital in North India from January 2010 to December 2016 were reviewed. Culture data were evaluated; the organisms were noted and their antimicrobial susceptibilities were analysed. The microbiological profile and antimicrobial susceptibility pattern of CF patients were evaluated. Results: A total of 445 samples from 146 children were processed, of which 246 (55%) samples showed bacterial growth. Mixed infections 48 (19.5%) were common in older children. Children aged 3-6 months (62.5%) showed the highest culture positivity. The most commonly isolated organisms were Pseudomonas aeruginosa (52.6%) and Staphylococcus aureus. Children with initial cultures positive for P. aeruginosa had 55% of their subsequent cultures showing polymicrobial infections. P. aeruginosa was most susceptible to ciprofloxacin (89%) and piperacillin-tazobactum (88%). Among the staphylococcal isolates, 38% were methicillin-resistant S. aureus (MRSA). The percentage of MRSA increased from 66% in 2010 to 75% in 2012, followed by a decline to 24% in 2016. Conclusions: The pattern of airway colonisation in the Indian setting is different from the Caucasian population, and P. aeruginosa and Burkholderia cepacia complex appear early. Colonisation with P. aeruginosa benefits from therapy. In case of infection, care must be taken while initiating empiric therapy. It should be based on local antibiograms to prevent the emergence of resistant microbes.

Serodiagnostic evaluation of recombinant CdtB of S. Typhi as a potential candidate for acute typhoid.

Typhoid fever caused by human restricted Salmonella typhi presents a considerable health burden on developing South-Asian nations like India. The suboptimal sensitivity and specificity associated with culture-based isolation of etiological agent and the extensively used surface antigen-based serological assays often lead to misdiagnosis and inappropriate antimicrobial treatment. The increasing reports of the emergence of resistant strains and undefined disease burden signify the critical need for an inexpensive, reliable, easy-to-use, and highly sensitive diagnostic test for typhoid fever. Utilizing S. typhi-specific and immunogenic antigens in sero-diagnostic assays could lead to precise diagnosis of acute typhoid and prompt treatment. In this study, we report cloning, expression, and purification of recombinant Cytolethal distending toxin subunit B (CdtB) of S. typhi, which is reported to be highly specific, immunogenic, and expressed only upon S. typhi infection. We further evaluated the purified recombinant CdtB for its diagnostic potential in an IgM-based indirect ELISA format using 33 human samples. Twenty-one serum samples from blood culture confirmed cases (n = 21) of typhoid and 12 samples from healthy controls (n = 12) were tested. The assay showed sensitivity of 100% and specificity of 83.3% respectively with positive and negative predictive values of 91.3 and 100% respectively. Efficient detection of specific IgM antibodies indicates that CdtB could be highly valuable in sero-diagnosis of acute typhoid and rapid screening of clinical samples.

An outbreak of Burkholderia cepacia complex in the paediatric unit of a tertiary care hospital.

INTRODUCTION: Burkholderia cepacia complex (Bcc) has emerged as a serious nosocomial pathogen worldwide especially in patients with indwelling catheters and cystic fibrosis. Bcc is a common contaminant of pharmaceutical products. We describe an outbreak of Bcc bacteraemia amongst children admitted in Paediatric Intensive Care Unit (PICU) and paediatric ward at a tertiary care hospital, Mumbai, in Western India. MATERIALS AND METHODS: Blood culture samples from paediatric patients yielded growth of non-fermenting, oxidase positive, motile, Gram negative bacilli (NFGNB) (76/909) over a period of 8 months. Based on conventional biochemical tests and antimicrobial susceptibility testing, these isolates were provisionally identified as Bcc. The increased, repeated and continued isolation of Bcc alerted the possibility of an outbreak confined to PICU and paediatric ward. Active surveillance was undertaken to trace the source and contain the outbreak. Isolates were subjected to recA polymerase chain reaction (PCR) and Expanded multilocus sequence typing (EMLST). RESULTS: Surveillance revealed the presence of Bcc on the upper surface of rubber stopper of sealed multidose amikacin vials. Isolates from blood culture and rubber stoppers were confirmed as Bcc by recA PCR. EMLST revealed that these isolates shared an identical novel sequence type 824 proving clonality. Timely interventions instituted led to control of the outbreak. CONCLUSION: This study highlights the importance of identification and molecular characterization of Bcc to establish its role in infection and outbreak.

Infection Profile in Chronic Granulomatous Disease: a 23-Year Experience from a Tertiary Care Center in North India.

PURPOSE: Chronic granulomatous disease (CGD) is an inherited phagocytic disorder characterized by recurrent infections with usually catalase-positive organisms. Infections in CGD from developing countries are expected to be different from those in the Western countries. We report the profile of infections in children diagnosed with CGD from a tertiary care center in North India. METHODOLOGY: Case records of children diagnosed with CGD at Pediatric Immunodeficiency Clinic, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India, from August 1993 to April 2016 (23 years) were analyzed. RESULTS: Thirty-eight children were diagnosed to have CGD. Median follow-up of patients was 2 years (interquartile range 0.75, 6.0). Staphylococcus aureus and Pseudomonas spp. were the two most common causative bacteria isolated. Aspergillus was the most common fungus isolated. The most common organ involved was the lung (94.7%). Liver abscesses were identified in 5 patients (13.2%), and 20 (52.6%) patients had lymphadenitis. Infections with Pseudomonas spp. were high in our cohort (15.7%) compared to the other studies. Infections with some unusual organisms (e.g., Fusarium dimerium and Chryseobacterium gleum) were also seen in our cohort. Children with X-linked CGD presented earlier and also had a greater number of infections as compared to autosomal recessive CGD. CONCLUSIONS: Various socioeconomic factors coupled with the lack of awareness and paucity of readily available diagnostic facilities for primary immunodeficiencies accounted for a late clinical presentation with severe infections and increased mortality (28.9%) in our cohort. However, mortality was similar in X-linked and autosomal recessive CGD as was the number of fungal infections. The incidence of infections and mortality was significantly lower after initiation of antibacterial and antifungal prophylaxis.

Bacillus cereus causing intratumoral brain abscess.

We report a case of intratumoral brain abscess due to Bacillus cereus in an adult male patient, which was managed successfully with excision of lesion and piperacillin-tazobactam for the duration of 5 weeks. To the best of our knowledge, this is a first case report of B. cereus infection leading to intratumoral brain abscess in a patient with a history of steroid administration by the intravenous route.

Multilocus sequence analysis reveals high genetic diversity in clinical isolates of Burkholderia cepacia complex from India.

Burkholderia cepacia complex (Bcc) is a complex group of bacteria causing opportunistic infections in immunocompromised and cystic fibrosis (CF) patients. Herein, we report multilocus sequence typing and analysis of the 57 clinical isolates of Bcc collected over the period of seven years (2005-2012) from several hospitals across India. A total of 21 sequence types (ST) including two STs from cystic fibrosis patient's isolates and twelve novel STs were identified in the population reflecting the extent of genetic diversity. Multilocus sequence analysis revealed two lineages in population, a major lineage belonging to B. cenocepacia and a minor lineage belonging to B. cepacia. Split-decomposition analysis suggests absence of interspecies recombination and intraspecies recombination contributed in generating genotypic diversity amongst isolates. Further linkage disequilibrium analysis indicates that recombination takes place at a low frequency, which is not sufficient to break down the clonal relationship. This knowledge of the genetic structure of Bcc population from a rapidly developing country will be invaluable in the epidemiology, surveillance and understanding global diversity of this group of a pathogen.

Clinical and in vitro evidence for the antimicrobial therapy in Burkholderia cepacia complex infections.

Treatment of infections caused by Burkholderia cepacia complex (Bcc) in cystic fibrosis (CF) patients poses a complex problem. Bcc is multidrug-resistant due to innate and acquired mechanisms of resistance. As CF patients receive multiple courses of antibiotics, susceptibility patterns of strains from CF patients may differ from those noted in strains from non-CF patients. Thus, there was a need for assessing in vitro and clinical data to guide antimicrobial therapy in these patients. A systematic search of literature, followed by extraction and analysis of available information from human and in vitro studies was done. The results of the analysis are used to address various aspects like use of antimicrobials for pulmonary and non-pulmonary infections, use of combination versus monotherapy, early eradication, duration of therapy, route of administration, management of biofilms, development of resistance during therapy, pharmacokinetics-pharmacodynamics correlations, therapy in post-transplant patients and newer drugs in Bcc-infected CF patients.

Comparison of the efficacy of chlorhexidine gluconate versus povidone iodine as preoperative skin preparation for the prevention of surgical site infections in clean-contaminated upper abdominal surgeries.

PURPOSE: To compare the efficacy of chlorhexidine-gluconate versus povidone iodine in preoperative skin preparation in the prevention of surgical site infections (SSIs) in clean-contaminated upper abdominal surgeries. METHODS: This was a prospective randomized controlled trial conducted on patients undergoing clean-contaminated upper abdominal surgeries. A total of 351 patients 18-70 years old were randomized into two groups; chlorhexidine and povidone iodine skin preparation before surgery. RESULTS: The incidence of SSIs in the chlorhexidine group was 10.8 %, in comparison to 17.9 % in the povidone iodine group. The odds ratio was 0.6 in favor of chlorhexidine use, but the results were not statistically significant (P = 0.06). In the first postoperative week, SSIs developed in 7 % of patients in the chlorhexidine group and 14.1 % in the povidone iodine group (P = 0.03), and in the second postoperative week, SSIs were present in 4.1 % of the patients in the chlorhexidine group and 4.4 % in the povidone iodine group, which was not statistically significant (P = 0.88). CONCLUSIONS: The incidence of SSIs after clean-contaminated upper abdominal surgeries was lower with the use of chlorhexidine skin preparation than with povidone iodine preparation, although the results were not statistically significant. However, the odds ratio between the two groups favored the use of chlorhexidine over povidone iodine for preventing SSIs.

Antithymocyte globulin-induced acute lung injury during transplantation for aplastic anemia.

A 10-year-old boy with acquired, very severe aplastic anemia developed acute lung injury after the administration of equine antithymocyte globulin, during conditioning for allogenic bone marrow transplantation. Limited cases of antithymocyte globulin-induced acute lung injury have been described in adults. The respiratory worsening was sudden and required mechanical ventilation. The clinical course was complicated by sepsis with Escherichia coli, vancomycin-resistant enterococci, and Stenotrophomonas maltophilia. Implications for treatment are discussed and earlier literature is reviewed.