colistin and Neonatal-Sepsis

Sepsis is one of the major causes of neonatal deaths in India and worldwide. Pathogens encountered in neonatal sepsis vary worldwide; reports from developing countries more commonly show Gram negative organisms, most common being Acinetobacter spp., Klebsiella spp. and Escherichia coli. Recent studies show that the incidence of antimicrobial resistance, to third generation cephalosporins and carbapenems, has been on a rise. Because of widespread antimicrobial resistance, 'Higher' or 'Reserve' antibiotics are increasingly being used as first/second line antibiotics. In the past decade, there has been a resurgence in the use of colistin as a result of Extended-spectrum β-lactamase (ESBL)- producing Enterobacteriaceae and carbapenem resistant Enterobacteriaceae (CRE), which retain susceptibility only to colistin. The increasing burden of drug resistant Gram negative organisms, particularly Acinetobacter spp., Klebsiella spp., and E. coli might pose a formidable threat in coming years.

Topics: Anti-Bacterial Agents; beta-Lactamases; Blood Culture; Carbapenems; Colistin; Drug Resistance, Multiple; Enterobacteriaceae; Escherichia coli; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; India; Klebsiella; Neonatal Sepsis

Increased use of colistin in healthcare necessitates studies on the trend of colistin resistance and the underlying mechanisms.. To understand the susceptibility trend and molecular mechanisms of colistin resistance in neonatal isolates over a 12 year period.. Colistin susceptibility, mRNA expression, whole genome sequence and mutational analysis was performed. Phylogenomic comparison with a global collection of colistin-resistant Klebsiella pneumoniae strains (n = 70) was done.. Of 319 Enterobacterales (K. pneumoniae and Escherichia coli) studied, colistin resistance was found in 9 K. pneumoniae (2.8%). The transmissible colistin resistance gene, mcr, was absent. Colistin-resistant K. pneumoniae belonged to diverse sequence types (ST14/37/101/147/716) and exhibited multiple mechanisms of colistin resistance including overexpression of the two-component systems (TCS) (phoP/Q, pmrA/B), and AcrAB-TolC pump and its regulators. Mutations in TCS, mgrB, pumps, repressors, and lipopolysaccharide-modifying genes were detected. Phylogenomic comparison revealed that this global collection of colistin-resistant K. pneumoniae was diverse, with the presence of epidemic and international clones. Mutations in mgrB and TCS noted in global strains were comparable to the study strains. Co-occurrence of carbapenem resistance (n = 61, 87%) was observed in global strains. Co-existence of dual carbapenemases (blaNDM-5 with blaOXA-48/181) in multiple lineages within different replicons was found in neonatal colistin-resistant study isolates only.. Colistin resistance both in study and global strains is multifaceted and attributed to mutations in chromosomal genes leading to lipopolysaccharide modification or efflux of colistin through pumps. With no transmissible mcr, prevalence of colistin-resistant strains was low in this unit. Colistin-resistant strains with dual carbapenemases causing sepsis are alarming as they are practically untreatable.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Escherichia coli; Humans; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Lipopolysaccharides; Microbial Sensitivity Tests; Neonatal Sepsis; Phylogeny

Enterobacter kobei is an emerging cause of outbreak of nosocomial infections in neonatal intensive care units (NICUs). Between July and September 2016, a NICU in a tertiary care hospital of Nepal observed an abrupt increase in the number of neonatal sepsis cases caused by Enterobacter spp. infecting 11 out of 23 admitted neonates, five of whom died of an exacerbated sepsis.. To confirm the suspected outbreak, identify environmental source of infection, and characterize genetic determinants of antimicrobial resistance (AMR) and virulence of the pathogen.. Whole-genome sequencing of all Enterobacter spp. isolated from blood cultures of septic neonates admitted to NICU between May 2016 and December 2017 was performed. Also, an environmental sampling was intensified from fortnightly to weekly during the outbreak.. The genomic analysis revealed that 10 out of 11 non-duplicated E. kobei isolated from neonatal blood cultures between July and September 2016 were clonal, confirming the outbreak. The isolates carried AMR genes including bla. Our study underscored the need to implement stringent infection control measures to prevent infection outbreaks. For the first time, we report the emergence of carbapenem and colistin non-susceptible E. kobei carrying mcr-10 gene as a cause of nosocomial neonatal sepsis in a NICU.

Topics: Carbapenems; Colistin; Cross Infection; Disease Outbreaks; Enterobacter; Enterobacteriaceae Infections; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Microbial Sensitivity Tests; Neonatal Sepsis; Nepal; Tertiary Care Centers

Mobile colistin resistance (

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; China; Colistin; Enterobacter; Microbial Sensitivity Tests; Neonatal Sepsis; Plasmids

Infections with multidrug-resistant organisms (MDROs) such as Gram-negative bacteria have high morbidity and mortality with limited treatment options. Colistin, an antibiotic active against MDRO, was rarely used due to frequent adverse effects, but its use has now been recommended among adults. In this study, we determined the efficacy of colistin for the treatment of sepsis in neonates.. We conducted a retrospective record review of all neonates admitted to the neonatal intensive care unit of Aga Khan University Hospital, Karachi, Pakistan, between June 2015 and June 2018, who had sepsis and received colistin by intravenous, inhalation and/or intrathecal routes. Predictors of colistin efficacy, for neonatal survival and microbial clearance, were assessed using multiple logistic regression.. 153 neonates received colistin; 120 had culture-proven sepsis; and 93 had MDR-GNB (84 colistin-sensitive). 111 (72.5%) neonates survived and were discharged from hospital; 82.6% had microbial clearance. Neonates with colistin-sensitive bacteria (adjusted OR (AOR)=3.2, 95% CI 2.8 to 4.0), and those in which colistin therapy started early (AOR=7.2, 95% CI 3.5 to 13.6) were more likely to survive. Neonates with increased gestational age (AOR=1.9, 95% CI 1.5 to 3.0), higher weight (AOR=5.4, 95% CI 3.3 to 11.8) and later onset of sepsis (AOR=4.3, 95% CI 2.0 to 9.0) had higher survival. Adverse events included nephrotoxicity in 5.2%; 13.7% developed seizures and 18.3% had electrolyte imbalance.. Colistin therapy was associated with survival among neonates suffering from MDR-GNB sepsis. The frequency of side effects was moderate.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant, Newborn; Male; Neonatal Sepsis; Pakistan; Retrospective Studies; Tertiary Care Centers

The authors report a case of a premature male newborn admitted to the neonatal intensive care unit after an emergent caesarean due to maternal pre-eclampsia and foetal bradycardia at 32 weeks of gestational age and birth weight of 1440 g. There were no infection risk factors reported. On day 3 his clinical condition deteriorated, with tachycardia and subfebrile temperature and C-reactive protein at 1.25 mg/dL. Empirical antibiotics (flucloxacillin and gentamicin) were started, with no clinical improvement and C-reactive protein increasing to a maximum of 19 mg/dL (upper normal level of 1 mg/dL) after 3 days. Blood cultures from the third to the eighth day of life were positive for

Topics: Acinetobacter; Amikacin; Anti-Bacterial Agents; Central Venous Catheters; Colistin; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Male; Neonatal Sepsis; Parenteral Nutrition; Placenta; Pregnancy; Risk Factors

To determine the impact of using colistin for multidrug-resistant organisms in neonates.. This retrospective study was conducted at the Shifa International Hospital, Islamabad, Pakistan, and comprised microbiological data of babies from January 2010 to October 2012.The data was reviewed to identify the babies infected with multidrug-resistant organisms and who had received colistin therapy. SPSS 16 was used for data analysis.. Of the 30 neonates, 24(80%) were males and 6(20%) were females. Besides, 16(53.3%) neonates were preterm babies (< 37 weeks gestation). Two or more risk factors for multidrug-resistant organisms were present in 13(44%) babies. Mechanical ventilation was found in 26(87%) neonates and prior prolonged use of antibiotics in 7(23%). The commonest pathogen isolated was Acinetobacter, in 22(73%) cases. All isolates were susceptible to colistin but pan-resistant to multiple antibiotics, including cephalosporins, amikacin, meropenem and piperacillin/tazobactam. Colistin therapy was used for bacteraemia in 2(7%) cases, clinical sepsis 18(60%), pneumonia 2(7%) and tracheitis 8(26.7%). Moreover, 15(50%) neonates received both intravenous and aerosolised colistin while 9(30%) received aerosolised therapy alone.. Colistin therapy was well tolerated in neonates for the treatment of multidrug-resistant organisms.

Topics: Acinetobacter Infections; Administration, Inhalation; Administration, Intravenous; Anti-Bacterial Agents; Asphyxia Neonatorum; Bacteremia; Colistin; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant, Newborn; Infant, Premature; Male; Neonatal Sepsis; Pneumonia, Bacterial; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Retrospective Studies; Tracheitis

Topics: Administration, Intravenous; Colistin; Humans; Infant, Newborn; Neonatal Sepsis; Sepsis

Sepsis due to multidrug-resistant Gram-negative pathogens is a challenge for clinicians and microbiologists and has led to use of parenteral colistin. There is a paucity of data regarding safety and efficacy of intravenous colistin use in neonates. The objective of this retrospective analysis was to study the efficacy and safety of intravenous colistin in the treatment of neonatal sepsis.. An audit of the data from neonates, admitted to a neonatal intensive care unit of a tertiary care hospital during January 2012 to December 2012, and who received intravenous colistin was carried out.. Sixty two neonates received intravenous colistin (52 preterm and 10 term) for the treatment of pneumonia, bloodstream infections and meningitis. The isolated pathogens in decreasing order of frequency were Acinetobacter baumannii, Klebsiella pneumonia and Pseudomonas aeruginosa. Of the total 62 neonates, 41 (66.12%) survived and 21 (33.87%) died. Significantly higher mortality was observed in neonates with lower body weights (P < 0.05). A significant association of mortality was found in those with sepsis due to Klebsiella species. Only one of seven with this infection survived as against 15 of the 23 who grew other organisms [P = 0.03; crude odds ratio = 11.25 (1.2, 110.5)]. None of the neonates developed neurotoxicity or nephrotoxicity.. This retrospective study in neonates with sepsis showed that intravenous colistin was safe and effective in the treatment of neonatal sepsis. Further, well-controlled, prospective clinical trials need to be done to corroborate these findings.

Topics: Acinetobacter baumannii; Administration, Intravenous; Colistin; Female; Humans; Infant, Newborn; Klebsiella pneumoniae; Male; Meningitis; Neonatal Sepsis; Pneumonia; Pseudomonas aeruginosa; Tertiary Care Centers