A neonate born at 25 + 1/7 weeks developed ventilator-associated pneumonia at 29 + 3/7 weeks post-menstrual age with Escherichia coli that was originally sensitive to gentamicin. After 3 days of treatment with gentamicin, the minimum inhibitory concentration (MIC) changed from less than 1 mg/L to more than 16 mg/L. It appears that suboptimal gentamicin dosing led to the development of gentamicin resistance. As the patient was not improving clinically, the antibiotics were changed once the gentamicin resistance was identified. To minimize resistance and treatment failure, clinicians should consider the patient-specific pharmacokinetic parameters, achieved peak level, and the amount of time the gentamicin level will remain below the MIC of the organism being treated.
LeePLLeeWTChenHL. Ventilator-associated pneumonia in low birth weight neonates at a neonatal intensive care unit: a retrospective observational study. Pediatr Neonatol. 2017;58(1):16–21.
2.
CernadaMBrugadaMGolombekS, et al.Ventilator-associated pneumonia in neonatal patients: an update. Neonatology. 2014;105(2):98–107.
3.
GarlandJS. Ventilator-associated pneumonia in neonates: an update. NeoReviews. 2014;15(6):e225–235.
4.
Al-AlaiyanSBinmaneeA. Neonatal ventilator-associated pneumonia: an underdiagnosed problem in the neonatal intensive care unit. J Pediatr Neonatal Care. 2017;7(3):00288.
5.
FallahiMDashtASNaeempourN, et al.Ventilator-associated pneumonia in hospitalized newborns in a neonatal intensive care unit. Arch Pediatr Infect Dis. 2014;2(3):e16514.
6.
KrauseKMSerioAWKaneTR, et al.Aminoglycosides: an overview. Cold Spring Harb Perspect Med. 2016;6(6):a027029.
7.
YayanJGhebremedhinBRascheK. No development of imipenem resistance in pneumonia caused by Escherichia coli. Medicine (Baltimore). 2015;94(25):e1020.
8.
BartoloniAPallecchiLBenedettiM, et al.Multidrug-resistant commensal Escherichia coli in children, Peru and Bolivia. Emerg Infect Dis.2006;12(6):907–913.
9.
ColeBKLlikjMMcCloskeyCB, et al.Antibiotic resistance and molecular characterization of bacteremia Escherichia coli isolates from newborns in the United States. PLoS One. 2019;14(7):e0219352.
10.
MilatovicDBravenyI. Development of resistance during antibiotic therapy. Eur J Clin Microbiol. 1987;6(3):234–244.
11.
OteoJLázaroEde AbajoFJ, et al.Spanish members of EARSS. Antimicrobial-resistant invasive Escherichia coli, Spain. Emerg Infect Dis. 2005;11(4):546–553.
EcheverriaPLewMASmithAL. Apparent emergence of aminoglycoside-resistant Escherichia coli during neonatal meningitis. N Engl J Med. 1975;293(18):913–914.
14.
YudinMHvan SchalkwykJVan EykN. No. 233-antibiotic therapy in preterm premature rupture of the membranes. J Obstet Gynaecol Can. 2017;39(9):e207–e212.
15.
Prelabor rupture of membranes. ACOG practice bulletin No. 188. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2018;131(1):e1–e14.
16.
FuchsABielickiJMathurS, et al.Reviewing the WHO guidelines for antibiotic use for sepsis in neonates and children. Paediatr Int Child Health. 2018;38(S1): s3–15.
17.
MunitaJMAriasCA. Mechanisms of antibiotic resistance. Microbiol Spectr. 2016;4(2). doi:10.1128/microbiolspec.VMBF-0016-2015
18.
FolgoriLEllisSJBielickiJA, et al.Tackling antimicrobial resistance in neonatal sepsis. Lancet Glob Health. 2017;5(11):e1066-e1068.
19.
PatelSJGreenNClockSA, et al.Gram-negative bacilli in infants hospitalized in the neonatal intensive care unit. J Pediatric Infect Dis Soc. 2017;6(3):227-230.
20.
WalkerOBabbCKarampatsasK, et al.Screening for colonisation with gentamicin-resistant Gram-negative organisms on the neonatal unit: does positive screening predict sepsis?Arch Dis Child Fetal Neonatal Ed. 2019;104(1):F113-F114.
21.
CarrDBarnesEHGordonA, et al.Effect of antibiotic use on antimicrobial antibiotic resistance and late-onset neonatal infections over 25 years in an Australian tertiary neonatal unit. Arch Dis Child Fetal Neonatal Ed. 2017;102(3):F244-F250.
22.
WangJZhangHYanJ, et al.Literature review on the distribution characteristics and antimicrobial resistance of bacterial pathogens in neonatal sepsis [published online ahead of print, February 26, 2020]. J Matern Fetal Neonatal Med. 2020;1-10.
23.
HasvoldJBradfordLNelsonC, et al.Gentamicin resistance among Escherichia coli strains isolated in neonatal sepsis. J Neonatal Perinatal Med. 2013;6(2):173-177.
24.
KentAKortsalioudakiCMonahanIM, et al.Neonatal gram-negative infections, antibiotic susceptibility and clinical outcome: an observational study. Arch Dis Child Fetal Neonatal Ed. 2016;101(6):F507-F512.
25.
FalagasMETansarliGSRafailidisPI, et al.Impact of antibiotic MIC on infection outcome in patients with susceptible gram-negative bacteria: a systematic review and meta-analysis. Antimicrob Agents Chemother. 2012;56(8):4214–4222.
26.
ClockSAFerngYHTabibiS, et al.Colonization with antimicrobial-resistant gram-negative bacilli at neonatal intensive care unit discharge. J Pediatric Infect Dis Soc. 2017;6(3):219-226.
27.
GullbergECaoSBergOG, et al.Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog. 2011;7(7):e1002158.
28.
Durante-MangoniEGrammatikosAUtiliR, et al.Do we still need aminoglycosides?Int J Antimicrob Agents. 2009;33(3):201–205.
CraigWA. Optimizing aminoglycoside use. Crit Care Clin. 2011;27(1):107–121.
31.
SalehifarERafatiMR. Extended-interval dosing of aminoglycosides in pediatrics: a narrative review. J Pediatr Rev. 2015;3(2):31–34.
32.
SafiKHDamianiJMSturzaJ, et al.Extended-interval aminoglycoside use in cystic fibrosis exacerbation in children and young adults: a prospective quality improvement project. Glob Pediatr Health. 2016;3:1–7.
33.
StablerSNEnsomMH. Extended-interval aminoglycoside therapy for adult patients with febrile neutropenia: a systematic review. Can J Hosp Pharm. 2011;64(3):182–191.
34.
MohamedAFNielsenEICarsO, et al.A pharmacokinetic-pharmacodynamic model for gentamicin and its adaptive resistance with predictions of dosing schedules in newborn infants. Antimicrob Agents Chemother. 2012;56(1):179–188.
35.
van DongeTPfisterMBielickiJ, et al.Quantitative analysis of gentamicin exposure in neonates and infants calls into question its current dosing recommendations. Antimicrob Agents Chemother. 2018;62(4):e02004–e02017.
36.
Gentamicin. IBM Micromedex NeoFax. Truven Health Analytics. 2018. Accessed May, 2020. www.micromedexsolutions.com
37.
RaoSCSrinivasjoisRMoonK. One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates. Cochrane Database Syst Rev. 2016;12:CD005091.
