Low vasopressin and progression of neonatal sepsis to septic shock: a prospective cohort study.

The study objective was to analyze the association between low plasma vasopressin and progression of sepsis to septic shock in neonates < 34 weeks gestation. Septic neonates of < 34 weeks gestation were consecutively enrolled; moribund neonates and those with major malformations were excluded. Subjects were monitored for progression of sepsis to septic shock over the first 7 days from enrolment. Plasma vasopressin levels and inducible nitric oxide synthase levels were measured at the onset of sepsis (T0), severe sepsis (T1), and septic shock (T2). Primary outcome was plasma vasopressin levels at the point of sepsis in those who progressed to septic shock in comparison with matched nested controls in the non-progression group. Forty-nine (47%) enrolled subjects developed severe sepsis or septic shock. Plasma vasopressin levels (pg/ml) at the onset of sepsis were significantly low in those who progressed to septic shock (median (IQR), 31 (2.5-80) versus 100 (12-156); p = 0.02). After adjusting for confounders, vasopressin levels were independently associated with progression to septic shock (adjusted OR (95% CI), 0.97 (0.96, 0.99); p = 0.01).Conclusion: Preterm septic neonates who progressed to septic shock had suppressed vasopressin levels before the onset of shock. Low vasopressin levels were independently associated with progression to septic shock.What is known:• In animal sepsis models and adult septic patients, exuberant production of nitric oxide metabolites and low vasopressin levels have been reportedly associated with progression to septic shock.• Vasopressin levels have been variably reported as low as well as elevated in children with septic shock.What is New:• Preterm neonates who progressed from sepsis to septic shock had significantly lower levels of vasopressin before the onset of shock in comparison with those who did not progress.• Low vasopressin levels independently predicted the progression from sepsis to septic shock in this population.

Randomized controlled trial of cefazolin monotherapy versus cefazolin plus azithromycin single dose prophylaxis for cesarean deliveries: A developing country's perspective.

AIM: To compare the efficacy of pre-incision intravenous single doses of cefazolin versus cefazolin plus azithromycin as an antibiotic prophylaxis in cesarean delivery (CD). METHODS: This was a single-center, double blind, randomized controlled trial conducted in the PGIMER, Chandigarh. 200 women undergoing elective/emergency cesarean section were randomized. Group A received single dose of cefazolin plus placebo while Group B received single dose of cefazolin plus azithromycin. Primary outcome evaluated was occurrence of surgical site infections (SSI); secondary outcomes included incidence of febrile morbidity, UTI, endometritis, neonatal outcome, total cost of antibiotics, and duration of hospital stay in both the study arms. Descriptive statistics and χ2 tests were used for analysis of the data. RESULT: There was an overall significant reduction in the incidence of SSI (15% vs 3%; P = 0.03), endometritis (8% vs 2%; P = 0.048), and post-operative febrile morbidity (17% vs 3%; P = 0.001) with the addition of azithromycin to cefazolin. Duration of hospital stay was almost two days lesser for the cefazolin plus azithromycin group. Subgroup analysis of patients with SSI showed the age, duration of ruptured membranes, and type of anesthesia as important predictors of infection rate. Study observed statistically significant reduction in requirement of additional post operative antibiotics, phototherapy for neonates, hospital stay and cost of therapy in cefazolin plus azithromycin group (P < 0.05). CONCLUSION: Tertiary care hospitals in developing countries such as India can opt for the cefazolin plus azithromycin as antimicrobial prophylaxis during CD to maximize the efficacy as well as for decreasing the cost burden of postoperative infections.

Deficiency of Interleukin-1 Receptor Antagonist (DIRA): Report of the First Indian Patient and a Novel Deletion Affecting IL1RN.

PURPOSE: Deficiency of interleukin-1 receptor antagonist (DIRA) is a rare life-threatening autoinflammatory disease caused by autosomal recessive mutations in IL1RN. DIRA presents clinically with early onset generalized pustulosis, multifocal osteomyelitis, and elevation of acute phase reactants. We evaluated and treated an antibiotic-unresponsive patient with presumed DIRA with recombinant IL-1Ra (anakinra). The patient developed anaphylaxis to anakinra and was subsequently desensitized. METHODS: Genetic analysis of IL1RN was undertaken and treatment with anakinra was initiated. RESULTS: A 5-month-old Indian girl born to healthy non-consanguineous parents presented at the third week of life with irritability, sterile multifocal osteomyelitis including ribs and clavicles, a mild pustular rash, and elevated acute phase reactants. SNP array of the patient's genomic DNA revealed a previously unrecognized homozygous deletion of approximately 22.5 Kb. PCR and Sanger sequencing of the borders of the deleted area allowed identification of the breakpoints of the deletion, thus confirming a homozygous 22,216 bp deletion that spans the first four exons of IL1RN. Due to a clinical suspicion of DIRA, anakinra was initiated which resulted in an anaphylactic reaction that triggered desensitization with subsequent marked and sustained clinical and laboratory improvement. CONCLUSION: We report a novel DIRA-causing homozygous deletion affecting IL1RN in an Indian patient. The mutation likely is a founder mutation; the design of breakpoint-specific primers will enable genetic screening in Indian patients suspected of DIRA. The patient developed anaphylaxis to anakinra, was desensitized, and is in clinical remission on continued treatment.