Article Figures & Data
Figures
- FIG. 1.
Timing of bacterial and fungal sepsis in VLBW infants. Percentages indicate the approximate number of VLBW infants with septicemia. EONS usually occurs via ascent of organisms from the birth canal to the amniotic fluid, with or without rupture of amniotic membranes. LONS occurs with vertical and horizontal spread of organisms. While the vast majority of cases of sepsis in VLBW infants occur in the first 30 days of life, VLBW infants requiring prolonged intensive care are at risk for VLONS beyond 2 months of age.
- FIG. 2.
Pathogenesis of fungal colonization and infection.
Tables
- TABLE 1.
Susceptibility of preterm infants to sepsis
Antimicrobial defense Preterm infant compromised defenses Epidermal and epithelial barriers Immature skin (3-6-cell stratum corneum and thin keratin layer) Insensible water loss from skin and humidification systems, creating moist skin that favors the growth of microorganisms Skin trauma from intensive care interventions Adherence of Candida to exposed intermediate epithelial cells, favoring colonization Enhanced adherence of Candida and GBS to buccal epithelial cells of preterm versus term infants, facilitating oral colonization Invasive catheters and tubes Surface for colonization provided by intravascular catheters breaching intact epidermis Proliferation due to parenteral nutrition and biofilms on plastic catheters Colonization of endotracheal and nasogastric tubes Trauma from endotracheal, suctioning, and nasogastric tubes Intact endothelial tissues Trauma to endothelium and endocardium from central vascular catheters Injury from hyperosmolar nutrition solutions and medications Gastrointestinal mucosa Decreased acid production Immature peristalsis and reduced absorption, favoring microorganism overgrowth Thin mucin layer, leading to decreased barrier function and secretory IgA binding Diminished number of intraepithelial lymphocytes FIP NEC Microflora Competitive bacterial microflora diminished by broad-spectrum antibiotics, favoring growth of resistant bacterial and fungal organisms More commensal gram-positive organisms selected for by human milk Complement Lower levels with decreasing gestational age Cytokines Decreased production of IL-1, IL-8, gamma interferon, TNF-α, G-CSF, and GM-CSF Defensins Diminished with decreasing gestational age Neutrophils Decreased bone marrow storage pools and G-CSF levels Immature neutrophil oxidative burst Decreased numbers of azurophilic granules Diminished granular contents (lactoferrin, defensins, lysozyme, myeloperoxidase, proteases, and cathepsin G) Possible impairment of function by medications (steroids, H2 antagonists, lipid emulsions) Monocytes Diminished number and function Decreased adherence at sites of infection Decreased opsonization and phagocytosis Diminished gamma interferon, IL-3, and G-CSF release T-cells, B-cells, and antibodies Decreased numbers of lymphocytes in gastrointestinal tract Majority of transfer of maternal IgGs after 32 weeks' gestation Decreased production of antibodies by preterm lymphocytes - TABLE 2.
Organisms and death rates associated with bloodstream infections in VLBW (<1,500 g) neonatesa
Organism EONS LONS No. of infections (% of total) Mortality (%)b No. of infections (% of total) Mortality (%)b Gram-positive bacteria (total) 31 (36.9) 26 922 (70.2) 11.2 GBS 9 (10.7) 30 (2.3) 21.9 Viridans streptococcus 3 (3.6) Other streptococci 4 (4.8) Listeria monocytogenes 2 (2.4) Coagulase-negative Staphylococcus 9 (10.7) 629 (47.9) 9.1 Staphylococcus aureus 1 (1.2) 103 (7.8) 17.2 Enterococcus species 43 (3.3) Other 3 (3.6) 117 (8.9) Gram-negative bacteria (total) 51 (60.7) 41 231 (17.6) 36.2 Escherichia coli 37 (44.0) 64 (4.9) 34.0 Haemophilus influenzae 7 (8.3) Citrobacter 2 (2.4) Bacteroides 2 (2.4) Klebsiella 1 (1.2) 52 (4.0) 22.6 Pseudomonas 35 (2.7) 74.4 Enterobacter 33 (2.5) 26.8 Serratia 29 (2.2) 35.9 Other 2 (2.4) 18 (1.4) Fungi (total) 2 (2.4) 160 (12.2) 31.8 Candida albicans 2 (2.4) 76 (5.8) 43.9 Candida parapsilosis 54 (4.1) 15.9 Other 30 (2.3) ↵ a NICHD Neonatal Network Survey, 1998 to 2000 (453, 454). A total of 5,447 patients with EONS and 6,215 patients with LONS were studied. There were a total of 84 bloodstream infections in the EONS patients (1.5% of the total) and 1,313 bloodstream infections in the LONS patients (21.1% of the total).
↵ b All-cause mortality.
- TABLE 3.
Diagnostic utility of CRP and cytokine measurements in predicting sepsis in VLBW infantsa
Study Infant population No. of patients No. of culture- proven sepsis events Time of testing Test Sensitivity (%) Specificity (%) PPV (%) NPV (%) Franz et al., 2001 (145) Preterm and term 709 (387 preterm) 14 Birth IL-8 NR NR 22-26 wk 93 (a) 55 (a) 27-29 wk 89 (a) 56 (a) 30-32 wk 83 (a) 77 (a) Kuster et al., 1998 (272) VLBW 125 21 >2 days IL-1ra 100 (a) 92 (a) NR NR IL-6 89 (b) 83 (b) CRP 50 (b) 93 (b) Ng et al., 1997 (340) VLBW 68 45 >3 days CRP + IL-6 98 (c) 91 (c) 90 (c) 98 (c) Chan and Ho, 1997 (77) VLBW 70 30 >3 days CRP 48 (d) 79 (d) 74 (d) 55 (d) Wagle et al., 1994 (487) <29 wk gestation 123 36 1-87 days CRP 90 (a) 81 (a) 48 (a) 98 (a) Seibert et al., 1990 (426) 23-31 wk gestation 125 8 Birth CRP 63 (a) 70 (a) 13 (a) 96 (a) 67 (b) 82 (b) 60 (b) 86 (b) 85 23 >3 days CRP 57 (a) 61 (a) 30 (a) 82 (a) 58 (b) 90 (b) 93 (b) 49 (b) ↵ a Selected studies are summarized with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) calculated for CRP and cytokine levels in VLBW infants. Tests were compared to different definitions of infection, which included culture-proven plus clinical sepsis (a), culture-proven sepsis (b), septicemia plus NEC plus microbiologically confirmed focal infection (c) or sepsis-like syndrome with positive blood, CSF, or joint fluid culture (d). Serial testing was performed in all studies except one (Chan et al.), but the number and timing of tests varied for the other studies. Positive values were defined as CRP ≥ 1.0 to 1.5 mg/dl, IL-6 ≥ 25 to 31 pg/ml, IL-8 ≥ 70 pg/ml, and IL-1 receptor antagonist (IL-1ra) ≥ 12,000 pg/ml. NR, not reported.
- TABLE 4.
Fungal colonization in VLBW and ELBW infantsa
Characteristic Results for study (study period) Baley et al. (30) (1983) Hageman et al. (183) (1985) Pappu-Katikaneni et al. (362) (1991) Rowen et al. (395) (1992) Saiman et al. (402) (1993-1995) Huang et al. (215) (1996) Kicklighter et al. (255) (1998-1999)b Kaufman et al. (246) (1998-2000)b Birth wt (gr) <1,500 <1,500 <1,500 <1,500 <1,500 <1,500 <1,500 <1,000 No. of patients 146 38 40 116 780 116 52b 50b % of patients with colonization 27 47 63 34 31 22 46 60 % of patients colonized with: C. albicans 16 24 40 26 18 13 44 44 C. papapsilosis 5 24 10 4 13 6 37 45 C. glabrata 0 0 0 3 <1 4 3 C. guilliermondii 0 0 0 0 <1 0 3 C. lusitaniae 0 0 0 0 0 11.1 5.1 C. tropicalis 2.1 0 2.5 1.7 0 3.7 0 Other 3.4 0 0 0 2.7c 0.8 0 1.1 % of total no. of patients colonized by site: Skin Groin or axilla 13.7 12.9 0 48 Umbilicus 8 Gastrointestinal tract Rectal 19.2 33.6 31 12.9 45 54 Stool 62.5 Respiratory tract Oropharyngeal 11 11.2d 6 Endotracheal 4.8 11.2d 2.6 42 Urine 8.3 7.7 % of total no. of patients with fungal sepsis 2.1 7.9 12.5 6.0 3.1 2.6 3.9 16 - TABLE 5.
Comparison of C. albicans, C. parapsilosis, and C. glabrata sepsisa
Characteristic Results for: P value C. albicans C. parapsilosis C. glabrata Baseline characteristics No. of patients 41 8 9 Gestational age (wk) 26.6 ± 0.5 27.3 ± 1.3 29.7 ± 1.2 0.01 Birth wt (g) 932 ± 75 965 ± 194 1,442 ± 292 0.02 No. (%) of VLBW (<1,500 g) infants 38 (93) 7 (88) 7 (78) NS No. (%) born via vaginal delivery 26 (63) 4 (50) 7 (78) NS Factors present at the diagnosis of fungemia Age at diagnosis (days) 17 (11-31) 25 (17-87) 14 (10-21) NS No. (%) on antibiotics 12 (38) 3 (38) 6 (67) NS No. (%) with apnea 28 (68) 4 (50) 2 (22) 0.01 Lowest platelet count (103/mm3) 74 ± 9 39 ± 2 124 ± 34 0.04 No. of positive blood cultures for fungus 2.1 ± 1.1 1.8 ± 0.71 2.0 ± 1.3 NS No. (%) with candiduria 15 (37) 2 (25) 2 (22) NS No. (%) with meningitis 5 (12) 1 (13) 1 (11) NS No. with renal abscessc/total no. tested (%) 5/38 (13) 1/7 (14) 0/7 (0) NS No. with cardiac vegetations/total no. tested (%) 2/30 (7) 0/6 (0) 0/8 (0) NS No. (%) with necrotizing enterocolitis 6 (15) 0 1 (11) NS No. (%) dying of Candida infection 0 0 0 NS No. (%) who died, all-cause mortality 3 (7) 0 0 NS ↵ a Data from reference 131. Plus-minus values are mean ± standard deviation. Median is given as 25th to 75th percentile.
b Significant difference between glabrata and non-glabrata groups (P < 0.05). NS, not significant.
↵ c Urinary tract ultrasound and echocardiogram were not performed on every patient.
- TABLE 6.
Summary of fluconazole prophylaxis study in ELBW infantsa
Characteristic Results for: P Fluconazole patients (n = 50) Placebo patients (n = 50) No. (%) of patients with fungal infectionb Blood, urine, or cerebrospinal fluid infection 0 (0) 10 (20) 0.008 Bloodstream infection 0 (0) 8 (16) 0.007 No. (%) of patients with fungal colonization One or more sites 11 (22) 30 (60) 0.002 Two or more sites 9 (18) 26 (52) 0.003 Skin 10 (20) 24 (48) 0.008 Gastrointestinal tract 9 (18) 27 (54) 0.003 Respiratory tract 1 (2) 21 (42) 0.002 Resistance (MIC50) (μg/ml) First 6 mo of study ≤2.0 ≤1.0 Last 6 mo of study ≤2.0 ≤1.0 Patient safety (liver function tests, mean ± SD) Aspartate aminotransferase (IU/liter) 27 ± 13 29 ± 16 0.67 Alanine aminotransferase (IU/liter) 21 ± 16 21 ± 19 0.85 Direct bilirubin (mg/dl) 0.6 ± 1.4 1.0 ± 1.8 0.34 Alkaline phosphatase (IU/liter) 305 ± 125 318 ± 182 0.70 No. (%) patients who died 4 (8) 10 (20) 0.22
- Top
- Article
- SUMMARY
- INTRODUCTION
- MICROORGANISMS AND VERY-LOW-BIRTH-WEIGHT INFANTS: SCOPE OF THE PROBLEM
- DEFINITIONS OF SEPSIS AND FOCAL INFECTIONS IN VERY-LOW-BIRTH-WEIGHT INFANTS
- DIAGNOSIS OF SEPSIS IN VERY-LOW-BIRTH-WEIGHT INFANTS
- BACTERIA
- FUNGAL ORGANISMS
- PREVENTION OF NOSOCOMIAL SEPSIS IN VERY-LOW-BIRTH-WEIGHT INFANTS
- CONCLUSION
- REFERENCES
- Figures & Data
- Info & Metrics