Antibiotic-Resistant Organisms in the Neonatal Intensive Care Unit

doi:10.1053/j.semperi.2007.01.004

Seminars in Perinatology

Volume 31, Issue 1, February 2007, Pages 26-32

https://doi.org/10.1053/j.semperi.2007.01.004 Get rights and content

Neonates, particularly those born prematurely, are at an increased risk of bacterial infection. Empiric treatment with antimicrobials occurs frequently in the neonatal intensive care unit (NICU). Repeated and/or prolonged courses of antibiotic exposure have resulted in an increase in the prevalence of hospital-acquired, antibiotic-resistant organisms such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and multidrug-resistant Gram-negative rods. As bacterial strains become increasingly resistant to standard antimicrobial therapy, measures to control and prevent this problem are essential. Current efforts have focused on monitoring and restricting the use of antimicrobials, proper hand hygiene, evaluation of potential reservoirs of bacterial acquisition and transmission, cohorting and isolation of colonized infants, decolonization strategies, and fostering of effective inter- and intrahospital communication.

Section snippets

Methicillin-Resistant Staphylococcus aureus (MRSA)

Neonates are exposed to and subsequently colonized with S. aureus at or shortly after birth or during contact with adult skin or the environment after delivery.⁴ The major reservoir of S. aureus in the neonate is the umbilical cord, with other common sites of colonization including, but not limited to, the skin, nasopharynx, and gastrointestinal tract.⁴ By 10 days of life, approximately 80% of neonates are colonized with S. aureus.4, 5 Despite this high rate of colonization, attack rates of

Vancomycin-Resistant Enterococci (VRE)

Vancomycin-resistant enterococci have emerged as important health care-associated pathogens, particularly in urinary tract and wound infections.³⁵ Once rare, vancomycin-resistant strains of enterococci are now common and are endemic in many hospitals.³⁶ In the 2004 CDC’s National Nosocomial Infections Surveillance System (NNISS) report, 28.5% of enterococcal isolates were vancomycin-resistant.³⁷

Enterococci have developed high level antibiotic resistance to multiple antibiotics primarily due to

Multidrug Resistant Gram-Negative Rods

Gram-negative rods (GNR) are a frequent cause of early-onset sepsis (EOS; typically ≤3 days of life) and late-onset sepsis (LOS; >3 days of life), particularly in very low birth weight (VLBW; BW <1500 g) neonates, with Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia marcescens, and Enterobacter cloacae among the most common species cultured.1, 2, 65 GNR sepsis in this population is also associated with considerable morbidity and mortality.3, 66, 67 Increasing

Summary

The increase in the frequency of preterm births⁹⁶ coupled with increased intrapartum and postnatal antibiotic exposure in this population is becoming a significant dilemma. As many bacterial isolates are no longer susceptible to the common antimicrobial agents utilized in the NICU, therapeutic options are becoming limited, frequently leading to treatment with bacteriostatic agents, unproven combinations of antibiotics, or experimental drugs.35, 36, 59, 72, 74 Efforts to halt the global spread

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Although antibiotics used prophylactically and therapeutically have likely saved millions of newborns over the past century, their widespread use, both antenatally and postnatally, may not be completely benign. Antibiotic-resistant organisms seem to be an exponentially growing problem. Strong associations with biologic plausability based on animal studies of the evolving immune system have been identified between neonatal antibiotic exposure and later health outcomes. Over the past several years, large, multicenter antibiotic stewardship efforts have been underway to more efficiently and effectively use antibiotics in newborn nurseries and neonatal intensive care units (NICUs). In this review, we will (1) describe the importance and current rationale of antibiotic use in newborns; (2) review the extent and variation in antibiotic practice in NICUs; (3) discuss the emergence of resistant organisms in neonatal infections; (4) present evidence identifying the links between antimicrobial exposure and short- and long-term clinical outcomes; and (5) discuss the importance and impact of antibiotic stewardship in this population.
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Early onset sepsis (EOS) remains a major cause of morbidity and mortality in newborns; however, current diagnostic tools are inadequate. We evaluated the accuracy of a novel cytokine, interleukin (IL)-35, for the diagnosis of EOS in comparison with other infection markers.
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Antibiotics remain the cornerstone for the treatment of neonatal sepsis. However, the indiscriminate use of antibiotics has resulted in the development of drug resistant strains and a surge for the development of newer antibiotics, which are expensive (Camacho-Gonzalez et al., 2013; Bizzarro and Gallagher, 2007; Kristof et al., 2007). Therefore, it is imperative to look for alternatives in a developing state like Odisha with a large population of poor people.
Vitamin D has potent antimicrobial and anti-inflammatory properties. Vitamin D deficiency has been shown to be associated with the risk of vulnerability to different infectious diseases, such as neonatal sepsis. Polymorphisms in vitamin D receptor (VDR) gene can influence the expression of vitamin D in individuals. Hence, it is essential to study the vitamin D status and VDR gene polymorphisms for assessing neonatal sepsis risk. In this study, we assessed the serum 25(OH)D, the main circulating form of vitamin D and VDR polymorphism on 120 subjects in a case-control approach, recruiting 60 subjects in each category. We genotyped Fok1, Bsm1, Apa1 and Taq1 gene polymorphisms in VDR by developing a unique mismatch amplification mutation assay (MAMA) and studied their association in both populations. VDR-MAMA primers were designed by addition of dual mismatches (DM) near the 3′ end and were selected based on high ΔCt values in comparison to single mismatch (SM) primers using SYBR-Green RT-PCR, which were eventually used for VDR genotyping. Genotyping was also performed using PCR-RFLP for further confirmation. Serum 25(OH)D ELISA revealed that cases were vitamin D insufficient (Median = 12.16 ng/ml, 95% CI: 3.84–22.22) and controls were vitamin D sufficient (Median = 30.22 ng/ml, 95% CI: 20.08–46.78; p < 0.0001) respectively, which indicated that vitamin D insufficiency was mostly prevalent in cases. We found no evidence of association between genotypes of the Apa1 polymorphism and neonatal sepsis or 25(OH)D serum levels. The distributions of the Fok1, Bsm1, and Taq1 genotypes were not consistent with Hardy-Weinberg equilibrium in the control group. Future studies in larger populations are required to establish whether the VDR polymorphisms can be potentially used as genetic markers for early screening towards predisposition to neonatal sepsis risk. In this study, we describe a simple, inexpensive and rapid screening of VDR gene polymorphisms using VDR MAMA-PCR, which can be used in both clinical and research laboratories.
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Antibiotic-Resistant Organisms in the Neonatal Intensive Care Unit

Section snippets

Methicillin-Resistant Staphylococcus aureus (MRSA)

Vancomycin-Resistant Enterococci (VRE)

Multidrug Resistant Gram-Negative Rods

Summary

Lancet

Curr Opin Pharmacol

J Hosp Infect

Drug Resist Updat

J Hosp Infect

J Hosp Infect

Lancet

Pathol Biol

J Hosp Infect

Mayo Clin Proc

J Hosp Infect

Int J Hyg Environ Health

Clin Lab Med

Am J Infect Control

Am J Obstet Gynecol

Am J Obstet Gynecol

Obstet Gynecol

Am J Infect Control

Seventy-five years of neonatal sepsis at Yale: 1928-2003

Pediatrics

Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network

Pediatrics

Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants

N Engl J Med

Staphylococcus aureus outbreaks among newborns: new frontiers in an old dilemma

Am J Perinatol

Staphylococcus aureus colonization and infection in newborn nursery patients

Am J Dis Child

Epidemiological analysis defining concurrent outbreaks of Serratia marcescens and methicillin-resistant Staphylococcus aureus in a neonatal intensive-care unit

Infect Control Hosp Epidemiol

Eradication of endemic methicillin-resistant Staphylococcus aureus infections from a neonatal intensive care unit

J Infect Dis

Outbreak of invasive disease caused by methicillin-resistant Staphylococcus aureus in neonates and prevalence in the neonatal intensive care unit

Pediatr Crit Care Med

Multiple methicillin-resistant Staphylococcus aureus strains as a cause for a single outbreak of severe disease in hospitalized neonates

Pediatr Infect Dis J

Methicillin-resistant Staphylococcus aureus in neonatal intensive care unit

Emerg Infect Dis

An outbreak of new, nonmultidrug-resistant, methicillin-resistant Staphylococcus aureus strain (sccmec type iiia variant-1) in the neonatal intensive care unit transmitted by a staff member

Pediatr Infect Dis J

Emergence of methicillin resistant Staphylococcus aureus (MRSA) bacteraemia among children in England and Wales, 1990-2001

Arch Dis Child

Unexpectedly prolonged colonization of exfoliative toxin A-producing methicillin resistant Staphylococcus aureus in infants

Eur J Pediatr

Methicillin-resistant Staphylococcus aureus colonization and its association with infection among infants hospitalized in neonatal intensive care units

Pediatrics

Effectiveness of contact isolation during a hospital outbreak of methicillin-resistant Staphylococcus aureus

Am J Epidemiol

An outbreak of neonatal toxic shock syndrome-like exanthematous disease (NTED) caused by methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal intensive care unit

Microbiol Immunol

Roles of 34 virulence genes in the evolution of hospital- and community-associated strains of methicillin-resistant Staphylococcus aureus

J Infect Dis

Management of outbreaks of methicillin-resistant Staphylococcus aureus infection in the neonatal intensive care unit: a consensus statement

Infect Control Hosp Epidemiol

Outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infections–Los Angeles County, California, 2002-2003

MMWR Morb Mortal Wkly Rep

Community-associated methicillin-resistant Staphylococcus aureus infection among healthy newborns–Chicago and Los Angeles County, 2004

MMWR Morb Mortal Wkly Rep

CA-MRSA infections an increasing concern in early infancy

AAP News

Community-associated methicillin-resistant Staphylococcus aureus in hospital nursery and maternity units

Emerg Infect Dis

Emergence of community-associated methicillin-resistant Staphylococcus aureus at a Memphis, Tennessee Children’s Hospital

Pediatr Infect Dis J

Staphylococcal resistance revisited: community-acquired methicillin resistant Staphylococcus aureus: an emerging problem for the management of skin and soft tissue infections

Curr Opin Infect Dis

Transmission of methicillin-resistant Staphylococcus aureus to preterm infants through breast milk

Infect Control Hosp Epidemiol

Transmission of community-associated methicillin-resistant Staphylococcus aureus from breast milk in the neonatal intensive care unit

Pediatr Infect Dis J

Vancomycin-resistant enterococci

Clin Microbiol Rev

National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004

Am J Infect Control