Introduction: The incidence of healthcare-associated multidrug resistant bacterial infections, particularly due to carbapenem resistant organisms, has been on the rise globally. Among these are the carbapenem resistant Acinetobacter baumannii and Enterobacteriaceae, which have been responsible for numerous outbreaks in neonatal units. The polymyxins (colistin and polymyxin B) are considered to be the last resort antibiotics for treating such infections. However, pharmacokinetic and pharmacodynamic data on the use of polymyxins in neonates and children are very limited, and there are safety concerns. Areas covered: In this review, the authors summarize the global burden of multidrug resistance, particularly carbapenem resistance, in the neonatal and paediatric population, and the potential wider use of polymyxins in treating these infections. Expert opinion: Both colistin and polymyxin B have similar efficacy in treating multidrug resistant infections but have safety concerns. However, polymyxin B appears to be a better therapeutic option, with more rapid and higher steady state concentrations achieved compared to colistin and less reported nephrotoxicity. There is virtually no data in neonates and children currently; there is therefore an urgent need for pharmacokinetic and safety trials in these populations to determine the optimal drug and dosing regimens and provide recommendations for their use against carbapenem resistant infections.

Introduction: Multidrug-resistant, Gram-negative infections, particularly due to carbapenem resistant organisms (CRO), have increased globally. Few studies have reported on the burden of CRO in neonates from low-middle income countries (LMIC). This study aimed to determine the incidence and mortality rates of culture-confirmed Gram-negative infections, with a special focus on CRO in a neonatal unit from a LMIC.Materials and Methods: Positive bacterial cultures from sterile sites of infants admitted in the neonatal unit from the 1^st January 2018 to 31^st December 2019, were reviewed retrospectively. Type of organism, susceptibility and outcomes were recorded. Data on Gram-negative isolates, including the CRO, were extracted. Rates and outcomes were analysed.Results: There were 2219 neonates with organisms isolated from sterile sites (blood and cerebrospinal fluid), accounting for 30% of all admissions, giving a neonatal sepsis incidence of 17.9/1000 patient-days. There was a total of 1746 positive isolates (excluding coagulase negative Staphyloccocus). Of these, 1706 (98%) were isolated from blood, and 40 (2%) from cerebrospinal fluid. Overall, 1188 (68%) were Gram-negative, 371 (21%) Gram-positive and 187 (10.7%) fungal isolates. The common Gram-negatives were Acinetobacter baumannii (526/1188;44%) and Klebsiella pneumoniae (469/1188;40%). Carbapenem resistance was observed in 359 (68%) of the Acinetobacter baumannii (CRAB) and in 103 (18%) of the Enterobacterales (CRE) isolates, with 98% of CRE being Klebsiella pneumoniae (CR-Klebs). Twenty-four (41%) of Pseudomonas species were carbapenem resistant. Overall, carbapenem resistance was seen in 42% of all Gram-negative organisms. The rate of CRAB and CRE were 2.9 and 0.8/1000 patient-days respectively. The overall, all-cause in-hospital mortality rate in infants with Gram-negative isolates was 22%, with higher mortality rate in those infected with CRO compared to non-CRO (34% vs 13%; OR 3.44; 95% CI 2.58–4.60; p < 0.001). The mortality rate in infants with CRE was higher than those with CRAB (48% vs 33%; OR 1.85; 95% CI 1.18–2.89; p = 0.007).Conclusion: We observed a high incidence of positive cultures from sterile sites. The common organisms isolated were Gram-negatives, and among these carbapenem resistance was high and was associated with high mortality. Mortality was higher in infants with CRE compared to those with CRAB.

Objective: To determine trends in incidence, etiology and antimicrobial susceptibility of blood and cerebrospinal fluid (CSF) culture confirmed infections in hospitalized infants in a large tertiary neonatal unit in South Africa. Methods: Single-center, retrospective review of laboratory records of bacteria and fungi, and their susceptibility profiles, isolated from blood and CSF of infants hospitalized in the neonatal unit at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, from 1^st January 2010 to 31^st December 2019. Laboratory data on isolates and their antimicrobial susceptibilities were collected. Coagulase-negative Staphylococcus, Corynebacteria and Bacillus spp. were excluded. Patient-level clinical and laboratory data were not available. Results: There were 8,319 significant isolates, giving an infection rate of 14.3/1000 patient-days. Infection rates increased from 12.0 to 15.7/1000 patient-days (estimated average yearly change 0.6[95%CI, 0.5–0.7];p = <0.001). Gram-negative infection rates increased from 4.3 to 10.8/1000 patient-days (estimated average yearly change 0.7[95%CI,0.6–0.8];p = <0.001). The 2 most commonly isolated Gram-negative organisms were Acinetobacter baumannii (44%) and Klebsiella pneumoniae (39%). Carbapenem resistance was seen in 31% of all Gram-negatives and increased over time (estimated average yearly change 4.8%[95%CI,4.2%-5.3%];p<0.001). Gram-positive infection rates decreased (estimated average yearly change -0.1[95%CI,-0.2– -0.05];p = <0.001). Staphylococcus aureus was the most common Gram-positive isolated. Rates of methicillin-resistant Staphylococcus aureus decreased from 91% to 55%(estimated average yearly change -2.8%[95%CI,-3.5%–2%],p< 0.001). Rates of fungal isolates decreased (estimated average yearly change -0.06[95%CI,-0.1 –-0.02]);p = 0.007). Candida parapsilosis (52%) and Candida albicans (35%) were the most common fungi isolated. Conclusions: There has been a marked overall increase in rates of blood and/or CSF infections, with an absolute increase in Gram-negative infections observed, replacing Gram-positive and fungal pathogens. Extended spectrum beta-lactamase Gram-negative isolates are being replaced by carbapenem resistance, with around one third of all significant Gram-negative isolates now carbapenem resistant. Research into hospital based novel treatment and prevention interventions for neonatal sepsis should be urgently prioritized.

Introduction: The burden of sepsis in neonates due to Acinetobacter baumannii (A. baumannii) in developing countries is not well reported. The objective of this study was to determine prevalence of culture confirmed sepsis due to A. baumannii, antimicrobial susceptibility and case-fatality rates (CFR) due to this organism. Methodology: A retrospective review of medical and laboratory records of neonates admitted to a tertiary government hospital from a developing country was conducted. Records of neonates with positive microbiological cultures from blood or cerebrospinal fluid due to A. baumannii were reviewed for demographic characteristics, clinical presentation, laboratory findings, antibiotic susceptibility and outcome at hospital discharge. Results: There were 399 isolates of A. baumannii cultured from sterile sites, with a prevalence of 4.3/1000 live births or 22.8/1000 admissions, accounting for 13% of all culture confirmed sepsis. Majority of neonates were preterm (91%) with a mean gestational age and birth weight of 30 weeks and 1400 grams respectively. Antimicrobial susceptibility of isolates was 64% to cephalosporins, 21% to aminoglycosides and 17% were extremely-drug resistant (XDR), only susceptible to colistin. The CFR was 32%. Factors associated with mortality were presence of a central venous catheter prior to onset of sepsis (49% vs 31%, p = 0.03); need for mechanical ventilation (62% vs 36%, p = 0.005) and inotropic support (57% vs 17%, p < 0.001). Conclusions: A. baumannii is a significant pathogen causing sepsis in neonates, with 17% of them being XDR. It is associated with high CFR. These findings highlight the need for strict enforcement of infection control and antibiotic stewardship practices.

Available tests to diagnose infection in neonates often provide results after 12-24 hours. A bedside test that is reliable will facilitate earlier exclusion or diagnosis of infection. To validate a bedside C-reactive protein (CRP) test against the currently available laboratory CRP test in neonates with suspected sepsis. This was a prospective observational study where a bedside CRP was done concurrently with and validated against a laboratory CRP in neonates with suspected sepsis. The sensitivities, specificities and predictive values for the bedside CRP tests were calculated using the laboratory CRPs as the reference test. There were 209 measured CRP-sample pairs. Seventy per cent of these had suspected early-onset neonatal sepsis and 30% had suspected late-onset neonatal sepsis. Twelve per cent had culture-proven sepsis. At the recommended cut-off of 8.0 mg/L for the bedside CRP test, the sensitivity, specificity, positive and negative predictive values were 84%, 80%, 30% and 97%, respectively. Adjusting the cut-off value from 8.0 to 15.0 mg/L improved the specificity to 88%. The sensitivity, specificity and positive and negative predictive values were not different between early-onset and late-onset sepsis. The receiver operating characteristic curve had an area below the curve of 0.84 for the cut-off at 16.2 mg/L on the beside CRP test. The bedside CRP test may be used as a screening test to aid decisions to either commence or discontinue antibiotics in circumstances where the clinical diagnosis of sepsis is in doubt. By using a cut-off of 16.0 mg/L for the bedside CRP test, the possibility of a false negative result is minimised.