Pathogen-Specific Early Mortality in Very Low Birth Weight Infants with Late-Onset Sepsis: A National Survey

Makhoul, Imad R.; Sujov, Polo; Smolkin, Tatiana; Lusky, Ayala; Reichman, Brian

doi:10.1086/426444

Cited by 127 publications

(86 citation statements)

References 22 publications

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“…As in other studies on neonatal CoNS infections that have demonstrated significant morbidity but a low rate of mortality, there were no deaths associated with SHN sepsis at our institution (15,23). The incidence and types of infection associated with SHN in hospitalized patients are not known as, like others, our laboratory does not routinely identify CoNS to the species level.…”

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confidence: 65%

Nosocomial Spread of a Staphylococcus hominis subsp. novobiosepticus Strain Causing Sepsis in a Neonatal Intensive Care Unit

Cháves¹,

García–Álvarez²,

Sanz³

et al. 2005

J Clin Microbiol

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From 2002 to 2003, 32 isolates of Staphylococcus hominis subsp. novobiosepticus (SHN) were recovered from 21 patients, 18 of whom were neonates, with 13 considered to have late-onset SHN sepsis. All isolates from neonates had an indistinguishable pulsed-field gel electrophoresis pattern. Our data support SHN as an important nosocomial pathogen in neonates.Coagulase-negative staphylococci (CoNS) are now recognized as a major cause of nosocomial infections in neonatal intensive care units (NICUs) (8) and are responsible for 48% of late-onset sepsis among very-low-birth-weight neonates (20). Although Staphylococcus epidermidis causes 60 to 93% of CoNS bloodstream infections, several other CoNS species are reported to cause disease in infants (10,11,18). Recently, a novel subspecies of Staphylococcus hominis, S. hominis subsp. novobiosepticus (SHN), was isolated from blood cultures and other clinical specimens (6, 12). The name derives from the combination of novobio, pertaining to the property of novobiocin resistance, and septicus, pertaining to the ability to cause sepsis. After isolating SHN from several blood cultures at the NICU during 2002 and 2003, we undertook a retrospective study in our 1,300-bed tertiary care institution to determine the prevalence of this subspecies, the clinical significance of the isolates, and whether the infections were clonal in origin.Clinical records of patients from whom SHN had been isolated were reviewed. Diagnosis of sepsis was based on the assessment of the attending physician. For NICU patients, true infection was defined either by isolation of SHN from two separate blood cultures or by a single SHN-positive blood culture and an elevated serum level of C-reactive protein (Ն2 mg/dl). Blood samples were inoculated and processed in an automated system (BacT/Alert [BioMérieux, Durham, NC] or BACTEC 9240 [BD Diagnostics, Sparks, MD]). The type strain of SHN (ATCC 700236) was used as a reference standard throughout the investigations. Identification and susceptibility testing were performed using conventional methods and the Wider system (Soria Melguizo, Madrid, Spain) (3, 16). A zone of inhibition measuring Յ15 mm in Mueller-Hinton agar or Յ11 mm on Trypticase soy agar plates was considered indicative of novobiocin resistance (12). All isolates of SHN underwent confirmatory PCR analysis for the mecA gene (7). To confirm the identification of SHN, broad-spectrum primers were used for sequencing the 5Ј ends of both strands of the 16S rRNA gene (2, 6) using an ABI Prism 3100 genetic analyzer (Applied Biosystems, Foster City, CA). Further molecular characterization of SHN isolates was performed by pulsed-field gel electrophoresis (PFGE) following digestion of DNA extracts with SmaI (5).During 2002 and 2003, 32 isolates of SHN were recovered from 21 patients. Twenty-three isolates were from blood cultures, six were from catheters, one was from cerebrospinal fluid (CSF), one was from a wound, and one was from external ear fluid. All 21 patients yielded an SHN-positive blood culture. A...

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confidence: 65%

Nosocomial Spread of a Staphylococcus hominis subsp. novobiosepticus Strain Causing Sepsis in a Neonatal Intensive Care Unit

Cháves¹,

García–Álvarez²,

Sanz³

et al. 2005

J Clin Microbiol

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“…There are conflicting reports as to whether this has resulted in an increase in the absolute numbers of episodes of early-onset sepsis caused by gram-negative bacteria (25,33,37), but there is evidence to suggest that antimicrobial resistance is increasing in those gram-negative isolates associated with both early-and lateonset neonatal sepsis (17,35,37). In a report from Washington, DC, 17% of infants admitted to a NICU became colonized with antibiotic-resistant Enterobacteriaceae strains, and 14% of colonized infants developed infection (36).…”

Section: Discussionmentioning

confidence: 99%

“…A recent report from the Israeli Neonatal Network (25) estimates that sepsis due to Enterobacter spp., Escherichia spp., and Klebsiella spp. is associated with a 4.1-fold, 4.3-fold, and 6.3-fold risk of mortality, respectively, in the verylow-birth-weight population compared to that of sepsis associated with coagulase-negative staphylococci.…”

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confidence: 99%

Colonization and Persistence of Antibiotic-Resistant Enterobacteriaceae Strains in Infants Nursed in Two Neonatal Intensive Care Units in East London, United Kingdom

et al. 2008

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Stool samples were collected from infants nursed in two neonatal intensive care units (NICUs) in East London, United Kingdom. The aim of the study was to determine the incidence of and risk factors for the carriage of multiresistant Enterobacteriaceae strains (MRE; resistant to three or more classes of antibiotic) and the extent of the persistence of resistant strains following discharge. Sixty-two (50%) of 124 infants had acquired MRE by 2 weeks of postnatal age, and 69 (56%) infants had acquired MRE by discharge. The proportions of infants at 2 weeks carrying strains that were resistant to antibiotics were the following: tetracycline, 79%; amoxicillin, 78%; cephalosporins, 31%; trimethoprim, 20%; piperacillin-tazobactam, 11%; chloramphenicol, 9%; and aminoglycoside, 4%. A gestational age of less than 26 weeks was a risk factor for colonization with MRE at discharge, but not at 2 weeks. Analysis within a NICU showed that exposure of an infant to a specific antibiotic in the NICU was not a risk factor for the carriage of a strain resistant to that antibiotic. Estimates of persistence from discharge to 6 months were the following: for tetracycline, 57% ( Gram-negative infection is a major cause of mortality in infants (38). A recent report from the Israeli Neonatal Network (25) estimates that sepsis due to Enterobacter spp., Escherichia spp., and Klebsiella spp. is associated with a 4

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“…eonatal bacterial sepsis, exacerbated by neonatal immunodeficiency (1), remains a major cause of mortality and morbidity in newborns (2). Vancomycin is widely used for the treatment of late-onset sepsis caused by methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci in neonatal intensive care units (NICUs) (3); however, the clinical use of vancomycin is still hampered by its narrow therapeutic index and high pharmacokinetic variability (4).…”

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confidence: 99%

Clinical Utility and Safety of a Model-Based Patient-Tailored Dose of Vancomycin in Neonates

Leroux

Jacqz-Aigrain

Biran

et al. 2016

Antimicrob Agents Chemother

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N eonatal bacterial sepsis, exacerbated by neonatal immunodeficiency (1), remains a major cause of mortality and morbidity in newborns (2). Vancomycin is widely used for the treatment of late-onset sepsis caused by methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci in neonatal intensive care units (NICUs) (3); however, the clinical use of vancomycin is still hampered by its narrow therapeutic index and high pharmacokinetic variability (4). Indeed, de Hoog et al. reported that vancomycin clearance and half-life varied between 0.63 and 1.4 ml/ kg/min and between 3.5 and 10 h in neonates, respectively (4). The common adverse effects of vancomycin are nephrotoxicity and ototoxicity; however, it has been shown that neonates tolerated vancomycin better than adults. Safety data for a high dosing regimen and long-term follow-up are still lacking.The pharmacokinetic modeling approach is often applied to evaluate and optimize antimicrobial therapy in neonates (5). To date, vancomycin is one of the best-studied antimicrobials, and numerous studies have been conducted to characterize its pharmacokinetic parameters and to identify individual factors influencing variability (6). However, the clinical application of modelbased personalized vancomycin therapy is still limited. The objective of the present study was to evaluate the clinical utility and safety of a patient-tailored dose of vancomycin in neonates. Model-based patient-tailored dose of vancomycin. Special training was conducted in each NICU. We first informed the staff of the clinical pharmacology of vancomycin, its pharmacokinetic variability, and a large variation of dosage schedules currently used. We then explained the principles of individual dosage adaptation and how we developed the Excel dosing calculator using the results from our published population pharmacokinetic model (6). MATERIALS AND METHODS Neonates receiving vancomycin as a continuous infusion in one of threeIn order to calculate the patient-tailored dosing of vancomycin for each neonate, neonatologists had to enter four patient covariates in the calculator, including birth weight (in grams), current weight (in grams), postnatal age (PNA; in days), and serum creatinine concentration (in micromoles per liter) measured within 48 h of starting vancomycin treatment. The developed calculator was locked, and no other information was required. The patient-tailored dose is calculated automatically by using the following pharmacokinetic equations.Maintenance dose ϭ Target concentration ϫ CL ϫ 24 hwhere the loading dose is in milligrams, the maintenance dose is in milligrams per 24 h, the target concentration is in milligrams per liter, V (vol-

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Pathogen-Specific Early Mortality in Very Low Birth Weight Infants with Late-Onset Sepsis: A National Survey

Cited by 127 publications

References 22 publications

Nosocomial Spread of a Staphylococcus hominis subsp. novobiosepticus Strain Causing Sepsis in a Neonatal Intensive Care Unit

Nosocomial Spread of a Staphylococcus hominis subsp. novobiosepticus Strain Causing Sepsis in a Neonatal Intensive Care Unit

Colonization and Persistence of Antibiotic-Resistant Enterobacteriaceae Strains in Infants Nursed in Two Neonatal Intensive Care Units in East London, United Kingdom

Clinical Utility and Safety of a Model-Based Patient-Tailored Dose of Vancomycin in Neonates

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