Abstract
Objective
Over the last 20 years, a number of medical innovations with impact on the incidence of bacterial and fungal bloodstream infections (BSIs) in children have been developed and implemented. Although appropriate empirical antimicrobial therapy is a prerequisite to the successful treatment of BSIs, to date, epidemiological data on long-term microbiological trends in BSIs of hospitalized children have not been available.
Methods
Two cohorts of pediatric patients who were hospitalized in a single-center tertiary care hospital in Germany over a 20-year time span (period A from 1985 to 1995 vs. period B from 1997 to 2006) were retrospectively analyzed and compared with respect to the epidemiology and microbiology of BSIs.
Results
A total of 1,646 cases of monomicrobial BSIs were detected. The rate of positive blood culture results dropped from 4.5% in period A to 2.0% in period B. The proportion of gram-positive vs. gram-negative pathogens recovered from blood cultures remained stable. Among gram-positive pathogens, an increase in enterococci (3.3% vs. 8.2%) and in coagulase-negative staphylococci (CoNS) (22.9 vs. 28.2%) was observed. In contrast, BSIs caused by Staphylococcus aureus (16.4% vs. 11.7%), Streptococcus agalactiae (4.9% vs. 2.1%), Haemophilus influenzae (7.3% vs. 0.7%), and Neisseria meningitidis (1.9% vs. 0.5%) diminished. In analyzing subgroups, an increase of enterococcal and CoNS infections was noted among patients with immunosuppression and neonatal early-onset sepsis (EOS), while a decrease was found among late-onset sepsis (LOS) cases with S. viridans. Notably, aminopenicillin-resistant enterococci and aminopenicillin- and fluoroquinolone-resistant Enterobacteriaceae all increased over time, while the overall resistance pattern was still favorable. The overall mortality rate of BSIs decreased (5.2% vs. 2.6%).
Conclusions
Over the 20-year study period, the spectrum of specific microorganisms among BSIs shifted, with opportunistic pathogens becoming predominant. Despite an increase in the proportion of antibiotic-resistant organisms, however, the mortality rate decreased.
Similar content being viewed by others
Abbreviations
- ALL:
-
Acute lymphoblastic leukemia
- AML:
-
Acute myeloid leukemia
- BSI:
-
Blood stream infection
- CoNS:
-
Coagulase-negative staphylococci
- CVC:
-
Central intravascular catheter
- EOS:
-
Early-onset sepsis
- ESBL:
-
Extended spectrum beta-lactamase
- GBS:
-
Group B streptococci
- Hib:
-
Haemophilus influenzae type B
- JMML:
-
Juvenile monomyelocytic leukemia
- LOS:
-
Late-onset sepsis
- MCV:
-
Meningococcus C conjugate vaccine
- MDS:
-
Myelodysplastic syndrome
- NBSIs:
-
Nosocomial bloodstream infections
- NICU:
-
Neonatal intensive care unit
- n.a.:
-
Not available
- n.d.:
-
Not determined
- n.s.:
-
Non-significant
- PICU:
-
Pediatric intensive care unit
- PCV:
-
Pneumococcal conjugate vaccine
- RR:
-
Relative risk
- spp.:
-
Species
- vs.:
-
Versus
- 95%-CI:
-
95% confidence interval
References
Aquino VM, Pappo A, Buchanan GR, Tkaczewski I, Mustafa MM (1995) The changing epidemiology of bacteremia in neutropenic children with cancer. Pediatr Infect Dis J 14:140–143
Armenian SH, Singh J, Arrieta AC (2005) Risk factors for mortality resulting from bloodstream infections in a pediatric intensive care unit. Pediatr Infect Dis J 24:309–314
Banerjee SN, Emori TG, Culver DH, Gaynes RP, Jarvis WR, Horan T, Edwards JR, Tolson J, Henderson T, Martone WJ (1991) Secular trends in nosocomial primary bloodstream infections in the United States, 1980–1989: National Nosocomial Infections Surveillance System. Am J Med 91:86S–89S
Berner R, Schumacher RF, Bartelt S, Forster J, Brandis M (1998) Predisposing conditions and pathogens in bacteremia in hospitalized children. Eur J Clin Microbiol Infect Dis 17:337–340
Bilikova E, Babela R, Krcmery V (2003) Nosocomial enterococcal bacteremia in children. Pediatrics 111:445–446
Brodie SB, Sands KE, Gray JE, Parker RA, Goldmann DA, Davis RB, Richardson DK (2000) Occurrence of nosocomial bloodstream infections in six neonatal intensive care units. Pediatr Infect Dis J 19:56–65
Bruckner LB, Korones DN, Karnauchow T, Hardy DJ, Gigliotti F (2002) High incidence of penicillin resistance among alpha-hemolytic streptococci isolated from the blood of children with cancer. J Pediatr 140:20–26
Campos J, Hernando M, Román F, Pérez-Vázquez M, Aracil B, Oteo J, Lázaro E, de Abajo F; The Group of Invasive Haemophilus Infections of the Autonomous Community of Madrid, Spain (2004) Analysis of invasive Haemophilus influenzae infections after extensive vaccination against H. influenzae type b. J Clin Microbiol 42:524–529
Cohen ML (1992) Epidemiology of drug resistance: implications for a post-antimicrobial era. Science 257:1050–1055
Das I, Gray J (1998) Enterococcal bacteremia in children: a review of seventy-five episodes in a pediatric hospital. Pediatr Infect Dis J 17:1154–1158
Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL, Briggs JP, Lamm W, Clark C, MacFarquhar J, Walton AL, Reller LB, Sexton DJ (2002) Health care-associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 137:791–797
Gené A, Palacín E, García-García JJ, Muñoz-Almagro C (2005) Value of anaerobic blood cultures in pediatrics. Eur J Clin Microbiol Infect Dis 24:47–50
Goossens H, Ferech M, Vander Stichele R, Elseviers M; ESAC Project Group (2005) Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet 365:579–587
Gray J, Gossain S, Morris K (2001) Three-year survey of bacteremia and fungemia in a pediatric intensive care unit. Pediatr Infect Dis J 20:416–421
Gray JW (2004) A 7-year study of bloodstream infections in an English children’s hospital. Eur J Pediatr 163:530–535
Greenberg D, Moser A, Yagupsky P, Peled N, Hofman Y, Kapelushnik J, Leibovitz E (2005) Microbiological spectrum and susceptibility patterns of pathogens causing bacteraemia in paediatric febrile neutropenic oncology patients: comparison between two consecutive time periods with use of different antibiotic treatment protocols. Int J Antimicrob Agents 25:469–473
Grisaru-Soen G, Lerner-Geva L, Keller N, Berger H, Passwell JH, Barzilai A (2000) Pseudomonas aeruginosa bacteremia in children: analysis of trends in prevalence, antibiotic resistance and prognostic factors. Pediatr Infect Dis J 19:959–963
Grohskopf LA, Sinkowitz-Cochran RL, Garrett DO, Sohn AH, Levine GL, Siegel JD, Stover BH, Jarvis WR; Pediatric Prevention Network (2002) A national point-prevalence survey of pediatric intensive care unit-acquired infections in the United States. J Pediatr 140:432–438
Hall-Stoodley L, Costerton JW, Stoodley P (2004) Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol 2:95–108
Herz AM, Greenhow TL, Alcantara J, Hansen J, Baxter RP, Black SB, Shinefield HR (2006) Changing epidemiology of outpatient bacteremia in 3- to 36-month-old children after the introduction of the heptavalent-conjugated pneumococcal vaccine. Pediatr Infect Dis J 25:293–300
Hill PC, Wong CG, Voss LM, Taylor SL, Pottumarthy S, Drinkovic D, Morris AJ (2001) Prospective study of 125 cases of Staphylococcus aureus bacteremia in children in New Zealand. Pediatr Infect Dis J 20:868–873
Jones ME, Karlowsky JA, Draghi DC, Thornsberry C, Sahm DF, Bradley JS (2004) Rates of antimicrobial resistance among common bacterial pathogens causing respiratory, blood, urine, and skin and soft tissue infections in pediatric patients. Eur J Clin Microbiol Infect Dis 23:445–455
Klein JO, Marcy MS (2001) Bacterial sepsis and meningitis. In: Remington JS, Klein JO (eds) Infectious diseases of the fetus and newborn infant. Saunders, Philadelphia, pp 943–998
Pérez López A, Giménez M, Rodrigo C, Alonso A, Prat C, Ausina V (2003) Seven-year review of paediatric bacteraemias diagnosed in a Spanish university hospital. Acta Paediatr 92:854–856
Pittet D, Wenzel RP (1995) Nosocomial bloodstream infections. Secular trends in rates, mortality, and contribution to total hospital deaths. Arch Intern Med 155:1177–1184
Roberts GD, Washington JA 2nd (1975) Detection of fungi in blood cultures. J Clin Microbiol 1:309–310
Sard B, Bailey MC, Vinci R (2006) An analysis of pediatric blood cultures in the postpneumococcal conjugate vaccine era in a community hospital emergency department. Pediatr Emerg Care 22:295–300
Siegman-Igra Y, Fourer B, Orni-Wasserlauf R, Golan Y, Noy A, Schwartz D, Giladi M (2002) Reappraisal of community-acquired bacteremia: a proposal of a new classification for the spectrum of acquisition of bacteremia. Clin Infect Dis 34:1431–1439
Sohn AH, Garrett DO, Sinkowitz-Cochran RL, Grohskopf LA, Levine GL, Stover BH, Siegel JD, Jarvis WR; Pediatric Prevention Network (2001) Prevalence of nosocomial infections in neonatal intensive care unit patients: results from the first national point-prevalence survey. J Pediatr 139:821–827
Urrea M, Pons M, Serra M, Latorre C, Palomeque A (2003) Prospective incidence study of nosocomial infections in a pediatric intensive care unit. Pediatr Infect Dis J 22:490–493
Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC (2003) The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med 167:695–701
Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39:309–317
Wisplinghoff H, Seifert H, Tallent SM, Bischoff T, Wenzel RP, Edmond MB (2003) Nosocomial bloodstream infections in pediatric patients in United States hospitals: epidemiology, clinical features and susceptibilities. Pediatr Infect Dis J 22:686–691
Acknowledgments
The authors are grateful to Ursula Schmid, Käthe Brell, and Susanne Fukala for their excellent technical assistance.
Competing interests
The authors declare no conflict of interests.
Funding
P. Henneke was supported in part by grants from the Deutsche Forschungsgemeinschaft and the National Institutes of Health. M. Hufnagel was supported in part by an educational grant from the German Pediatric Infectious Disease Society.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hufnagel, M., Burger, A., Bartelt, S. et al. Secular trends in pediatric bloodstream infections over a 20-year period at a tertiary care hospital in Germany. Eur J Pediatr 167, 1149–1159 (2008). https://doi.org/10.1007/s00431-007-0651-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00431-007-0651-4