Incidence and All-Cause Mortality Rates in Neonates Infected With Carbapenem Resistant Organisms

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 1st January 2018 to 31st 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

Incidence, pathogens and antimicrobial resistance of blood and cerebrospinal fluid isolates from a tertiary neonatal unit in South Africa: A 10 year retrospective review.

ObjectiveTo 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.MethodsSingle-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 1st January 2010 to 31st 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.ResultsThere 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 = ConclusionsThere 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

Proportion of <i>Acinetobacter</i> and <i>Klebsiella</i> isolates cultured from blood and/or CSF that were carbapenem resistant, from 2010 to 2019.

Proportion of Acinetobacter and Klebsiella isolates cultured from blood and/or CSF that were carbapenem resistant, from 2010 to 2019.</p

Rates of blood and/or CSF infections for different pathogens over the 10-year period.

Rates of blood and/or CSF infections for different pathogens over the 10-year period.</p

Bacterial isolates from blood and/or CSF, per year, from 2010 to 2019.

Bacterial isolates from blood and/or CSF, per year, from 2010 to 2019.</p

Annual and total number and proportion of Gram-positive, Gram-negative and fungal isolates from 2010 to 2019.

Annual and total number and proportion of Gram-positive, Gram-negative and fungal isolates from 2010 to 2019.</p

Proportion of <i>Staphylococcus aureus</i> isolates with methicillin resistance cultured from blood and/or CSF, from 2010 to 2019.

Proportion of Staphylococcus aureus isolates with methicillin resistance cultured from blood and/or CSF, from 2010 to 2019.</p

Annual number of isolates, live births, admissions and patient-days, and annual infection rates from 2010 to 2019.

Annual number of isolates, live births, admissions and patient-days, and annual infection rates from 2010 to 2019.</p

Fig 1 -

Trends in A. live births, B. annual admissions, C. patient-days and D. blood and/or CSF isolates per 1000 patient days, from 2010 to 2019.</p

Dataset.

ObjectiveTo 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.MethodsSingle-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 1st January 2010 to 31st 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.ResultsThere 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 = 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%];pStaphylococcus 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%],pCandida parapsilosis (52%) and Candida albicans (35%) were the most common fungi isolated.ConclusionsThere 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.</div