search text   Advanced Search

This Article Abstract Full Text (PDF) P3Rs: Submit a response Alert me when this article is cited Alert me when P3Rs are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Byington, C. L. Articles by Pavia, A. T. Search for Related Content PubMed PubMed Citation Articles by Byington, C. L. Articles by Pavia, A. T. Related Collections Infectious Disease & Immunity Related AAP Red Book topics: Escherichia coli and Other Gram...

Serious Bacterial Infections in Febrile Infants Younger Than 90 Days of Age: The Importance of Ampicillin-Resistant Pathogens

Carrie L. Byington, MD^*,, Kristine K. Rittichier, MD, Kathlene E. Bassett, MD, Heidi Castillo, MD^*, Tiffany S. Glasgow, MD^*, Judy Daly, PhD^¶ and Andrew T. Pavia, MD

^* University of Utah Divisions of General Pediatrics
Pediatric Infectious Diseases
Pediatric Emergency Medicine
^¶ PCMC Microbiology Laboratory, Salt Lake City, Utah

-->

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
Background. Intrapartum antibiotic prophylaxis against group B Streptococcus (GBS) has reduced the occurrence of serious bacterial infections (SBI) in young infants caused by GBS. Recommendations for initial antibiotic therapy for the febrile infant 1 to 90 days old were developed when infections with GBS were common and antibiotic resistance was rare.

Objective. To document the pathogens responsible for SBI in recent years in febrile infants 1 to 90 days old and the antibiotic susceptibility of these organisms.

Methods. The results of bacterial cultures from infants 1 to 90 days old evaluated for fever at Primary Children’s Medical Center in Salt Lake City, Utah, between July 1999 and April 2002 were analyzed. Antibiotic susceptibility profiles were collected and patient records were reviewed to determine if initial antibiotic therapy was changed following the identification of the organism.

Results. Of 1298 febrile infants enrolled from the Primary Children’s Medical Center emergency department, 105 (8%) had SBI. The mean age of the infants with SBI was 39 days (range 2–82 days) and 2 (2%) were <7 days. SBI included urinary tract infection (UTI; 67%), bacteremia (16%), bacteremia and UTI (6%), bacteremia and meningitis (5%), meningitis (2%), abscess (2%), meningitis and UTI (1%), and meningitis and gastroenteritis (1%). Eighty-three (79%) of 105 episodes of SBI were caused by Gram-negative bacteria, including 92% of UTI, 54% of bacteremia, and 44% of meningitis cases. The most common pathogen was Escherichia coli (61%). Other Gram-negative pathogens were responsible for 19% of SBI. Staphylococcus aureus was the most common Gram-positive pathogen, causing 8% of SBI. GBS accounted for 6% of SBI.

Of the 105 pathogens, 56 (53%) were resistant to ampicillin. Of the pathogens causing meningitis, UTI, and bacteremia, 78%, 53%, and 50%, respectively, were resistant to ampicillin. Antibiotic therapy was changed in 54% of cases of SBI following identification of the organism.

Conclusions. In Utah, ampicillin-resistant Gram-negative bacteria are the most common cause of SBI in febrile infants <90 days old. This finding impacts antibiotic selection, especially in cases of meningitis. Local surveillance of pathogens and antibiotic susceptibility patterns is critical to determine appropriate antibiotic therapy.

Key Words: fever • infant • serious bacterial infection • ampicillin • antibiotic resistance

Abbreviations: GBS, group B Streptococcus • SBI, serious bacterial infection • UTI, urinary tract infection • ESBL, extended spectrum ß-lactamases • ampC, ampC ß-lactamases • PCMC, Primary Children’s Medical Center • ED, emergency department • CSF, cerebrospinal fluid

	INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
Febrile infants younger than 90 days are at risk for serious bacterial infection (SBI) including meningitis, bacteremia, and urinary tract infections (UTI).¹ Although practice varies regionally, most infants <28 days old are admitted to the hospital and receive antibiotics.² Infants between 29 and 90 days are frequently given antibiotics as well, although many are managed as outpatients.³

Traditionally, initial antibiotic coverage has included ampicillin with either gentamicin or a "third-generation" cephalosporin in infants 28 days and younger.⁴ A third-generation cephalosporin alone has been used in infants older than 28 days.^2,3 Recommendations for initial antibiotic coverage were developed when infections with group B Streptococcus (GBS) predominated and antibiotic resistance was rare. In recent years, the use of intrapartum antibiotic prophylaxis has reduced the incidence of early-onset infections caused by GBS.^5,6

Ampicillin has been used in young infants to treat suspected infections that were most often caused by GBS, ampicillin-sensitive Escherichia coli, Listeria monocytogenes, or Enterococcus species.⁴ Recent reports have suggested that ampicillin may be inadequate coverage because of the emergence of resistant organisms and because of changes in epidemiology of bacterial infections, especially increases in Gram-negative pathogens.^7,8

Third-generation cephalosporins have been used extensively in the past to provide coverage for Gram-negative pathogens. However, Gram-negative pathogens, especially members of the Enterobacteriaceae family such as Klebsiella and E coli, have developed plasmid-mediated extended spectrum ß-lactamases (ESBL) and Enterobacter, Citrobacter, and Serratia species have the ability to produce inducible ampC ß-lactamases (ampC) that render these bacteria cephem-resistant.^9,10 If appropriate testing for ESBL or ampC activity is not performed in the clinical microbiology laboratory, the bacterial isolate may be reported to be susceptible to third-generation cephalosporins when in fact it is resistant, placing the patient at risk for treatment failure.^9,11,12

Because of concerns regarding changing bacterial epidemiology and resistance to ampicillin and cephalosporins, we prospectively studied the results of bacterial cultures from febrile infants 1 to 90 days old to better define bacterial pathogens and antibiotic susceptibility patterns in our geographic area. We hypothesized that many infants with community-acquired late-onset (age 7 days) SBI would be infected with ampicillin-resistant Gram-negative pathogens.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
Approval to conduct this research was obtained by the Institutional Review Boards of the University of Utah and Primary Children’s Medical Center (PCMC) in Salt Lake City, Utah.

Patient Ascertainment
All the study subjects were infants who were participating in a prospective study regarding viral diagnostics in the management of the febrile infant. All febrile infants evaluated in the PCMC emergency department (ED) in Salt Lake City, Utah, were eligible for the study if they were 1 to 90 days old with temperatures of 38°C and were evaluated for sepsis between July 1, 1999 and April 8, 2002. Infants who had received any form of antibiotic therapy in the preceding 48 hours were not eligible. In the first 24 months of the study, infants whose parents were not approached for enrollment or whose parents did not give informed consent were not eligible. In the final 9 months of the study, Institutional Review Board approval was granted to review the records of all febrile infants evaluated in the PCMC ED.

PCMC is a 232-bed urban children’s hospital that serves as a community hospital for Salt Lake County, Utah, and as a tertiary referral center for the intermountain west. The ED evaluates 33 000 children per year with 650 of these febrile infants.

Review of Microbiologic and Medical Records
The computerized microbiologic records at PCMC were reviewed to capture any SBI in study infants. SBI was defined as any culture of blood, urine, cerebrospinal fluid (CSF), other normally sterile site, or stool positive for pathogenic bacteria. Urine cultures were considered positive if 100 000 colony forming units/ml of a single organism were isolated or if 50 000 to 99 000 colony forming units were isolated and the urinalysis was abnormal. For bacteria that could be considered contaminants, such as viridans Streptococci, SBI was diagnosed only if the infant had at least 2 positive cultures.

The antibiotic susceptibility for each pathogen was determined following recommendations of the National Committee of Clinical Laboratory Standards.^13–15 The microbiology laboratory began testing all invasive isolates of E coli and Klebsiella species for ESBL production in October of 1999 following National Committee of Clinical Laboratory Standards guidelines.^13–15 No standards exist for testing isolates for ampC production; therefore, none of the study isolates were screened.¹²

Medical records of all infants with SBI were reviewed. Specific information gathered included: age, gender, race/ethnicity, initial antibiotic therapy, and whether antibiotic therapy was changed following identification of positive bacterial culture. The microbiologic diagnosis of bacteremia, meningitis, UTI, or other infection was confirmed by review of the patient’s medical record. A subspecialist in pediatric infectious diseases (C.L.B.) made the final assignment of SBI. An infection was defined as community acquired if the infant had been at home for at least 3 days before the admission for SBI.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
Patient Ascertainment
Approximately 1800 infants were evaluated for fever and 1298 (72%) were eligible and included this study. A total of 105 infants (8%) were found to have SBI. Their mean age was 39 days (range: 2–82 days). A total of 103 of 105 (98%) of infants were 7 days of age or older. Further demographic information is shown in Table 1. The types of SBI seen in the study group are listed in Table 2. There were no cases of osteomyelitis or bacteremic pneumonia in the study infants. In all but 1 infant (age 2 days), episodes of SBI were classified as community acquired; however, 4 infants had prolonged or multiple hospitalizations before their hospitalizations for SBI.

For patients with bacteremia and/or meningitis with an ampicillin-resistant organism (N = 17), 11 had repeat cultures of blood or CSF before changing the antibiotic regimen and 7 cultures (64%) continued to be positive, demonstrating clinical failure of the initial regimen. The organisms isolated after at least 24 hours of antibiotic therapy included: S aureus-2, Klebsiella species-2, and 1 each of Citrobacter, Serratia, and Salmonella species. In 5 of 7 cases (71%), the infants had received gentamicin as part of their initial regimen and although the pathogens were susceptible in vitro, cultures remained positive.

Eighty-one of the Gram-negative isolates (98%) were members of the Enterobacteriaceae family known to be capable of producing ESBL and/or ampC.^9,10,16 There were no ESBL producers detected among study isolates of E coli or Klebsiella species. However, 2 infants younger than 28 days with meningitis (Serratia marcesens-1 and Citrobacter koseri-1) required treatment with a carbapenem antibiotic because therapy with a third-generation cephalosporin and gentamicin failed to clear their infections. The 2 isolates were susceptible to cefotaxime in vitro.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
In our study population of febrile infants 1 to 90 days old the rate of SBI was 8%. Other authors have noted similar rates of SBI.^17–19 Gram-negative pathogens were the cause of infection in almost 80% of the infants. E coli and Klebsiella species were the most common Gram-negative pathogens and accounted for 69% of SBI. The most common Gram-positive pathogens were S aureus (8%), GBS (6%), and Enterococcus (6%). No isolates of Listeria monocytogenes were identified. The pathogens isolated in this study differ significantly from the pathogens classically reported for this age group.⁴ GBS had been considered the most common pathogen in young infants in the United States for the last several decades.⁴

This study has several limitations. The data represent only infants admitted to a single children’s hospital in Utah. There may be unique factors in Utah that influence the bacterial pathogens isolated in this study. Infants included in this study represent only three fourths of all febrile infants evaluated at PCMC during the study period. However, we do not believe that there was any systematic bias in the enrollment of infants in the study. The study group is large and the occurrence of SBI is comparable to other large studies of febrile infants.¹ Finally, infants with SBI who did not have fever are not included in this data set. Despite the limitations, we believe the study documents important changes in bacterial epidemiology and antibiotic resistance that may be applicable to other geographic locations.

Gram-positive pathogens were responsible for only 20% of the infections in our study. Ampicillin resistance was significant in Gram-positive infections; 10 of 22 (45%) of Gram-positive isolates were resistant. Ampicillin resistance in Gram-positive pathogens was caused primarily by the appearance of S aureus as a pathogen of equal importance to GBS. Furthermore, S aureus was second only to E coli as a cause of bacteremia and meningitis. In the United States, S aureus was a major pathogen in this age group between the 1950s and 1970s and remains a significant pathogen today in the developing world.^20–22 Although no infants with S pneumoniae were identified in the study group, S pneumoniae is an important pathogen in this age group. Two cases of fatal pneumococcal sepsis in young infants occurred in our institution during the study period. One infant was afebrile at presentation and was thus not eligible for the study, and in the second instance, the infant died within hours of presentation and the parents were not approached for enrollment.

In this study, Gram-negative pathogens, especially E coli, were the most common cause of infection. Other studies have documented a similar increase in Gram-negative pathogens in neonates and infants over the last several years.^8,23,24 Of the 83 Gram-negative pathogens isolated in our study, 46 (55%) were resistant to ampicillin. Another recent US study found that >60% of Gram-negative pathogens isolated from outpatient infants 60 days or younger were resistant to ampicillin.⁸ Other authors have noted high rates of ampicillin resistance in neonates with early-onset E coli sepsis.^23–27

Seventy-four percent of the SBI isolates in this study were members of the Enterobacteraceae family known to produce ESBL and/or ampC. Although no ESBL activity was identified, 2 patients with Serratia and Citrobacter meningitis susceptible in vitro to cefotaxime failed treatment with a combination of cefotaxime and gentamicin. Others have reported clinical failures of cephalosporin therapy in Gram-negative pathogens susceptible to cephalosporins in vitro.⁹ The potential for the Gram-negative pathogens seen in this study to acquire ESBL or increase ampC production is substantial.^10,12,28 Infections with these pathogens will be more difficult to diagnose and treat and could result in higher morbidity and mortality than infections with GBS or ampicillin-susceptible E coli.²³

The factors contributing to the emergence of ampicillin-resistant pathogens in this age group are not well-described. Maternal antibiotic use during pregnancy and delivery as well as postnatal antibiotic exposure in the infant may all potentially influence the bacterial epidemiology of late-onset SBI. Increasing ampicillin resistance of pathogens isolated from neonates with early-onset sepsis has been associated with intrapartum ampicillin administration.^24,27 Data are lacking regarding the influence of maternal antibiotics given during labor and antibiotic resistance in late onset sepsis or SBI in infants. In this study, 22% of the isolates were pathogens uniformly resistant to ampicillin (Klebsiella sp.-8, S aureus-8, E cloacae-3, Citrobacter sp.-2, S marcesens-1, and Pseudomonas aeruginosa-1). We speculate that the appearance of these pathogens may be related to the intrapartum administration of ampicillin in our patient population. Approximately 30% of mothers in Salt Lake County receive intrapartum antibiotics, the majority of whom receive ampicillin rather than penicillin.²⁹ We are currently performing a prospective study to assess the impact of maternal antibiotics given during pregnancy, labor, and following delivery on the epidemiology of infection in infants 7 to 90 days old.

Because of the complexity associated with changing bacterial epidemiology and increasing antibiotic resistance, initial antibiotic selection for the febrile infant is becoming more challenging. In our patients, initial antibiotic therapy was changed in over half of the cases of SBI following identification of the pathogenic organism. Fortunately, most pathogenic bacteria will be identified in the first 24 hours of incubation.^30–32 Choosing an antibiotic regimen for a febrile infant before a specific organism is identified should be based on local bacterial epidemiology and resistance patterns. In addition, we believe that in cases of meningitis CSF Gram-stain results can help guide initial antibiotic selection.³³

The high rate of ampicillin-resistant infections in young infants in Utah raises concerns regarding the reliability of ampicillin in the antibiotic treatment regimens for febrile infants, especially those with meningitis. Nearly 80% of infants with meningitis were infected with ampicillin-resistant pathogens. Furthermore, 64% of patients with bacteremia or meningitis caused by ampicillin-resistant organisms had documented treatment failure of their initial antibiotic regimen. The majority of these failures occurred in infants receiving ampicillin and gentamicin. Based on the results of our data, we would recommend that the initial treatment of meningitis in infants 1 to 90 days old include a third-generation cephalosporin. We continue to support the use of ampicillin, especially in infants 60 days and younger because of the risk of GBS and enterococcal infections in this group. At our institution, infants younger than 60 days old with evidence of bacterial meningitis and a CSF Gram-stain that reveals no organisms may receive treatment during the first 24 hours after admission with ampicillin, gentamicin, and a third-generation cephalosporin in an effort to provide coverage for ampicillin-resistant pathogens and for GBS and Enterococci.

	CONCLUSIONS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 
Ampicillin-resistant pathogens are common causes of SBI in Utah. Other geographic areas have reported increases in ampicillin-resistant pathogens as well. Local monitoring of bacterial epidemiology and antibiotic susceptibility is crucial to guide physicians in their choice of antibiotics for the treatment of febrile infants. Initial antibiotic selection must be constantly refined until final bacterial identification and antibiotic susceptibilities are known. In cases of SBI with Enterobacteraceae, the physician must be aware of the potential for treatment failures with third-generation cephalosporins.^{9,10,16,34,35} Local monitoring of ESBL or ampC-producing Gram-negative pathogens¹² and S aureus in this age group is critical, as current recommendations for initial antibiotic therapy do not address infections caused by these pathogens. Research is needed to identify risk factors for the acquisition of antibiotic-resistant bacteria and strategies to help contain the transmission of these pathogens.

	ACKNOWLEDGMENTS

 
Dr. Byington was supported by the Robert Wood Johnson Generalist Physician Faculty Scholar Program. The investigation was supported by Public Health Services research grant M01-RR00064 from the National Center for Research Resources. This work was presented in part at the Pediatric Academic Societies Meeting, May 5, 2002, Baltimore, Maryland.

	FOOTNOTES

 
Received for publication Aug 28, 2002; Accepted Nov 12, 2002.

Address correspondence to Carrie L. Byington, MD, Department of Pediatrics, University of Utah, 50 N Medical Dr, Salt Lake City, UT 84132. E-mail: carrie.byington{at}hsc.utah.edu

	REFERENCES

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS REFERENCES

 

1. Baraff LJ, Oslund SA, Schriger DL, Stephen ML. Probability of bacterial infections in febrile infants less than three months of age: a meta-analysis. Pediatr Infect Dis J.1992; 11 :257 –264[ISI][Medline]
2. Baraff LJ, Bass JW, Fleisher GR, et al. Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Agency for Health Care Policy and Research. Ann Emerg Med.1993; 22 :1198 –1210[CrossRef][ISI][Medline]
3. Baskin MN, O’Rourke EJ, Fleisher GR. Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. J Pediatr.1992; 120 :22 –27[CrossRef][ISI][Medline]
4. Shapiro E. Fever without localizing signs. In: Long S, Pickering L, Prober C, eds. Principles and Practice of Pediatric Infectious Diseases. New York, NY: Churchill Livingstone, Inc; 1997:121–122
5. Schrag SJ, Zywicki S, Farley MM, et al. Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis. N Engl J Med.2000; 342 :15 –20[Abstract/Free Full Text]
6. Centers for Disease Control and Prevention. Prevention of Perinatal Group B Streptococcal Disease. MMWR Morb Mortal Wkly Rep. 2002;51 (No, RR-11)
7. Brown JC, Burns JL, Cummings P. Ampicillin use in infant fever: a systematic review. Arch Pediatr Adolesc Med.2002; 156 :27 –32[Abstract/Free Full Text]
8. Sadow KB, Derr R, Teach SJ. Bacterial infections in infants 60 days and younger: epidemiology, resistance, and implications for treatment. Arch Pediatr Adolesc Med.1999; 153 :611 –614[Abstract/Free Full Text]
9. Paterson DL, Ko WC, Von Gottberg A, et al. Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum ß-lactamases: implications for the clinical microbiology laboratory. J Clin Microbiol.2001; 39 :2206 –2212[Abstract/Free Full Text]
10. Pfaller MA, Jones RN. Antimicrobial susceptibility of inducible ampC ß-lactamase-producing Enterobacteriaceae from the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Programme, Europe 1997–2000. Int J Antimicrob Agents.2002; 19 :383 –388[CrossRef][ISI][Medline]
11. Tenover FC, Mohammed MJ, Gorton TS, Dembek ZF. Detection and reporting of organisms producing extended-spectrum ß-lactamases: survey of laboratories in Connecticut. J Clin Microbiol.1999; 37 :4065 –4070[Abstract/Free Full Text]
12. Thomson KS. Controversies about extended-spectrum and ampC ß-lactamases. Emerg Infect Dis.2001; 7 :333 –336[ISI][Medline]
13. National Committee of Clinical Laboratory Standards (NCCLS). M7A45-Methods for Dilution and Antimicrobial Susceptibility Testing for Bacteria that Grow Aerobically; 2000
14. National Committee of Clinical Laboratory Standards (NCCLS). M2–A7-Performance for Antimicrobial Disk-Susceptibility Testing: Approved Standard; 2000
15. National Committee of Clinical Laboratory Standards (NCCLS). M100–S12-Performance Standards for Antimicrobial Susceptibility Testing: Informational Supplement. 2002
16. Dunne EF, Fey PD, Kludt P, et al. Emergence of domestically acquired ceftriaxone-resistant Salmonella infections associated with ampC ß-lactamase. JAMA.2000; 284 :3151 –3156[Abstract/Free Full Text]
17. Baskin MN. The prevalence of serious bacterial infections by age in febrile infants during the first 3 months of life. Pediatr Ann.1993; 22 :462 –466[ISI][Medline]
18. Bonadio WA. Evaluation and management of serious bacterial infections in the febrile young infant. Pediatr Infect Dis J.1990; 9 :905 –912[ISI][Medline]
19. Kadish HA, Loveridge B, Tobey J, Bolte RG, Corneli HM. Applying outpatient protocols in febrile infants 1–28 days of age: can the threshold be lowered? Clin Pediatr.2000; 39 :81 –88[Abstract/Free Full Text]
20. Dixon RE, Kaslow RA, Mallison GF, Bennett JV. Staphylococcal disease outbreaks in hospital nurseries in the United States—December 1971 through March 1972. Pediatrics.1973; 51 :413 –417[Abstract/Free Full Text]
21. Karthikeyan G, Premkumar K. Neonatal sepsis: Staphylococcus aureus. as the predominant pathogen. Indian J Pediatr.2001; 68 :715 –717[Medline]
22. Schaffer T, Sylvester R, Jr, Baldwin J. Staphylococcal infections in newborn infants. II. Report of 19 epidemics caused by an identical strain of Staphylococcus pyogenes. Am J Public Health.1957; 47 :990
23. Levine EM, Ghai V, Barton JJ, Strom CM. Intrapartum antibiotic prophylaxis increases the incidence of Gram-negative neonatal sepsis. Infect Dis Obstet Gynecol.1999; 7 :210 –213[CrossRef][Medline]
24. Stoll BJ, Hansen N, Fanaroff AA, et al. Changes in pathogens causing early-onset sepsis in very-low-birth- weight infants. N Engl J Med.2002; 347 :240 –247[Abstract/Free Full Text]
25. Friedman S, Shah V, Ohlsson A, Matlow AG. Neonatal Escherichia coli. infections: concerns regarding resistance to current therapy. Acta Paediatr.2000; 89 ::686 –689[CrossRef][ISI][Medline]
26. Joseph TA, Pyati SP, Jacobs N. Neonatal early-onset Escherichia coli disease: the effect of intrapartum ampicillin. Arch Pediatr Adolesc Med.1998; 152 :35 –40[Abstract/Free Full Text]
27. Mercer BM, Carr TL, Beazley DD, Crouse DT, Sibai BM. Antibiotic use in pregnancy and drug-resistant infant sepsis. Am J Obstet Gynecol.1999; 181 :816 –821[CrossRef][ISI][Medline]
28. Venezia RA, Scarano FJ, Preston KE, et al. Molecular epidemiology of an SHV-5 extended-spectrum ß-lactamase in Enterobacteriaceae isolated from infants in a neonatal intensive care unit. Clin Infect Dis.1995; 21 :915 –923[ISI][Medline]
29. Gundlapalli A, Harbarth S, Stockdale W, Samore M. Shortage of penicillin G: impact on antibiotic prescribing at a tertiary care center. In: American Society for Microbiology, ed. 41st Interscience Conference on Antimicrobial Agents and Chemptherapy; 2001. Chicago, IL: American Society for Microbiology; 2001. Available at: www.asmusa.org/memonly/abstracts/AbstractsView.asp?AbstractID=58869
30. Kaplan RL, Harper MB, Baskin MN, Macone AB, Mandl KD. Time to detection of positive cultures in 28- to 90-day-old febrile infants. Pediatrics.2000; 106(6) . Available at: www.pediatrics.org/cgi/content/full/106/6/e74
31. Kumar Y, Qunibi M, Neal TJ, Yoxall CW. Time to positivity of neonatal blood cultures. Arch Dis Child Fetal Neonatal Ed.2001; 85 :F182 –F186[Abstract/Free Full Text]
32. McGowan KL, Foster JA, Coffin SE. Outpatient pediatric blood cultures: time to positivity. Pediatrics.2000; 106 :251 –255[Abstract/Free Full Text]
33. Dunbar SA, Eason RA, Musher DM, Clarridge JE, 3rd. Microscopic examination and broth culture of cerebrospinal fluid in diagnosis of meningitis. J Clin Microbiol.1998; 36 :1617 –1620[Abstract/Free Full Text]
34. Odeh R, Kelkar S, Hujer AM, et al. Broad resistance due to plasmid-mediated ampC ß-lactamases in clinical isolates of Escherichia coli. Clin Infect Dis.2002; 35 :140 –145[CrossRef][ISI][Medline]
35. Karas JA, Pillay DG, Muckart D, Sturm AW. Treatment failure due to extended spectrum ß-lactamase. J Antimicrob Chemother.1996; 37 :203 –204[Free Full Text]

This article has been cited by other articles:

				A. R. Schroeder, T. B. Newman, R. C. Wasserman, S. A. Finch, and R. H. Pantell Choice of Urine Collection Methods for the Diagnosis of Urinary Tract Infection in Young, Febrile Infants Arch Pediatr Adolesc Med, October 1, 2005; 159(10): 915 - 922. [Abstract] [Full Text] [PDF]

				T. S. Glasgow, P. C. Young, J. Wallin, C. Kwok, G. Stoddard, S. Firth, M. Samore, and C. L. Byington Association of Intrapartum Antibiotic Exposure and Late-Onset Serious Bacterial Infections in Infants Pediatrics, September 1, 2005; 116(3): 696 - 702. [Abstract] [Full Text] [PDF]

				T. D. Starner, B. Agerberth, G. H. Gudmundsson, and P. B. McCray Jr. Expression and Activity of {beta}-Defensins and LL-37 in the Developing Human Lung J. Immunol., February 1, 2005; 174(3): 1608 - 1615. [Abstract] [Full Text] [PDF]

				A. C. Rentz, M. H. Samore, G. J. Stoddard, R. G. Faix, and C. L. Byington Risk Factors Associated With Ampicillin-Resistant Infection in Newborns in the Era of Group B Streptococcal Prophylaxis Arch Pediatr Adolesc Med, June 1, 2004; 158(6): 556 - 560. [Abstract] [Full Text] [PDF]

				C. L. Byington, F. R. Enriquez, C. Hoff, R. Tuohy, E. W. Taggart, D. R. Hillyard, K. C. Carroll, and J. C. Christenson Serious Bacterial Infections in Febrile Infants 1 to 90 Days Old With and Without Viral Infections Pediatrics, June 1, 2004; 113(6): 1662 - 1666. [Abstract] [Full Text] [PDF]

				E. Parravicini GBS Maternal Prophylaxis Does Not Increase Non-GBS Infections in Newborns AAP Grand Rounds, January 1, 2004; 11(1): 2 - 3. [Full Text] [PDF]

This Article Abstract Full Text (PDF) P3Rs: Submit a response Alert me when this article is cited Alert me when P3Rs are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Byington, C. L. Articles by Pavia, A. T. Search for Related Content PubMed PubMed Citation Articles by Byington, C. L. Articles by Pavia, A. T. Related Collections Infectious Disease & Immunity Related AAP Red Book topics: Escherichia coli and Other Gram...

	Home | My Pediatrics | Journal Information | Current Issue | Past Issues | Subscriptions & Services | Contact Us Click here for faster international access © 2003 American Academy of Pediatrics. All rights reserved.