Antimicrobial resistance in colonizing group B Streptococci before the implementation of a Swedish intrapartum antibiotic prophylaxis program.

The prevalence of antibiotic resistance and their genetic determinants in colonizing group B streptococci (GBS) sampled in a Swedish nationwide survey was examined. In five GBS isolates (1.3%), kanamycin/amikacin resistance and the presence of the aphA-3 gene was identified. Three of these isolates carried the aad-6 gene and were streptomycin-resistant. Screening with kanamycin and streptomycin 1,000-µg disks enabled a rapid and easy detection of these isolates. In all, 312/396 (79%) GBS were tetracycline-resistant and 95% of the examined isolates harbored the tetM gene. Among the 22 (5.5%) GBS resistant to erythromycin and/or clindamycin, the ermB gene was detected in nine isolates (41%) and erm(A/TR) in ten isolates (45%). A high level of erythromycin and clindamycin resistance with minimum inhibitory concentrations (MICs) >256 mg/L was found in four serotype V isolates that harbored ermB. The erythromycin/clindamycin resistance was distributed among all of the common serotypes Ia, Ib, II, III, IV, and V, but was not present in any of the 44 serotype III isolates associated to clonal complex 17. Screening for penicillin resistance with 1-µg oxacillin disks showed a homogenous population with a mean inhibition zone of 20 mm. A change in the present oxacillin breakpoints for GBS is suggested.

Septicaemia and meningitis in neonates and during early infancy in the Göteborg area of Sweden.

UNLABELLED: In a retrospective study of neonatal septicaemia and meningitis carried out in 1987-1996 in the Göteborg area of Sweden, 305 cases during the first 28 d of life were found. The incidence was 3.7/1000 live births, which was higher than that found in a study from 1975 to 1986 in the same area, 2.8/1000 live births. The most common pathogens were group B streptococci, aerobic gram-negative rods, Staphylococcus aureus and enterococci. The cases were approximately equally divided between very early, early and late onset infections. The case-fatality rate was lower in the present study (9%) than that in the previous study (15%). The case-fatality rate varied between 23% in neonates with a gestational age of < or = 29 wk and 3% in full-term neonates. Eighty-three very late onset infections occurred between days 28 and 120 after birth, corresponding to an incidence of 1.0/1000 live births. Of those, 47 occurred in preterm neonates. The most common organisms were aerobic gram-negative rods. Coagulase-negative staphylococci (CoNS) were studied separately. This organism was isolated in 60 and 32 cases during the first 28 d of life and between days 28 and 120, respectively, in neonates fulfilling the criteria of the Yale-New Haven Hospital for infections caused by commensal species. The incidence rates of CoNS infections were 0.7 and 0.4/1000 live births, respectively. CONCLUSION: The incidence of neonatal infections increased and the case-fatality rate decreased in the Göteborg area compared to the findings of a previous study. Very late onset infections should be added to the total burden of neonatal infections. CoNS are important pathogens but their role is difficult to determine since they are both pathogens and contaminants of cultures from blood and cerebrospinal fluid.

Preterm infants with low immunoglobulin G levels have increased risk of neonatal sepsis but do not benefit from prophylactic immunoglobulin G.

OBJECTIVE: In a prospective, randomized, placebo-controlled, multicenter study, we evaluated the prevention of neonatal infections with intravenous immunoglobulin G (IVIgG) prophylaxis for preterm infants (gestational age <33 weeks) with umbilical cord blood IgG levels < or =4 g/L. STUDY DESIGN: Intravenous IgG or placebo (albumin), 1 g/kg body weight, was given on days 0, 3, 7, 14, and 21 to 81 infants with umbilical cord blood IgG levels < or =4 g/L: (1) IVIgG group, n = 40, mean (SD) gestational age 27.5 (2.2) weeks and birth weight 1.06 (0.39) kg; (2) placebo group, n = 41, mean (SD) gestational age 27.7 (2.5) weeks and birth weight 1.13 (0.38) kg. Infants with umbilical cord blood IgG levels >4 g/L (n = 238) served as a separate comparison group. Neonatal infections according to European Society of Pediatric Infectious Disease criteria were monitored until 28 days of life. RESULTS: Infants with IgG levels < or =4 g/L at birth who received IVIgG had no significant reduction in infectious episodes or mortality rate when compared with those given placebo. However, infants with a serum concentration of IgG >4 g/L at birth had significantly fewer infectious episodes (culture-proven sepsis) than infants with low serum concentrations of IgG (< or =4 g/L) when compared at the same gestational ages (26 to 29 weeks, P <.003). CONCLUSIONS: Prophylactic immunotherapy with IVIgG did not improve the immune competence in preterm infants with low serum IgG concentrations at birth. We speculate that a spontaneously high serum IgG concentration at birth reflects placenta function and is an indicator of a more mature immune system capable of protecting the preterm infant against severe neonatal infections.

Risk factors for neonatal sepsis in offspring of women with prelabor rupture of the membranes at 34-42 weeks.

One thousand three hundred eighty-five women with PROM (prelabor rupture of the membranes) participated in a prospective randomized study. Women with PROM were randomized to induction the following morning after PROM (early induction group) or induction two days later (late induction group). If contractions started within 2 hours after admission these women were included in the short latency group. All neonatal infections were classified as verified sepsis (positive culture) or clinical sepsis. The aim of the study was to compare the perinatal infectious outcome between the groups with different expectant managements in women with PROM and to study the association between demographic, intrapartum and postpartum variables and neonatal sepsis. In the short latency group one neonate had a proven sepsis while four neonates with proven sepsis were found in the early induction group. No proven sepsis was detected in the late induction group. Univariate analyses showed a significant association between clinical sepsis and: induction of labor (OR = 2.94, 95% CI 1.30-6.68), established labor 24.1-32 hours after ROM (OR = 5.89, 95% CI 1.68-20.63), established labor > 32 hours after ROM (OR = 4.59, 95% CI 1.52-13.87), time from ROM to delivery > 32 hours (OR = 5.07, 95% CI 1.40-18.39), cesarean section (OR = 11.03, 95% CI 4.10-29.68), chorioamnionitis before or during delivery (OR = 27.14, 95% CI 2.38-309.16), endometritis (OR = 18.08, 95% CI 1.82-179.87), CRP over 20 mg/l in the umbilical cord (OR = 17.12, 95% CI 5.68-52.12) and Apgar score < 7 after 1, 5 or 10 minutes. In a stepwise logistic regression analysis a significant association was found between clinical sepsis and cesarean section (OR = 10.08, 95% CI = 3.26-31.20), time from ROM to delivery > 32 h (OR = 3.74, 95% CI 1.62-8.62), gestational age 34-36 weeks (OR = 3.16, 95% CI 1.11-8.96) and parous women (OR = 2.41, 95% CI 1.04-5.57). In conclusion, this study indicates that that there was no difference in the incidence of neonatal infections between those with early and late induction. Clinical neonatal sepsis was associated with time from PROM to delivery over 32 hours, cesarean section, parous women and gestational age between 34 and 36 weeks.

Antibodies to group B streptococci in neonates and infants.

UNLABELLED: Invasive group B streptococcal (GBS) infections are common in neonates but are rare after the 1st month of life. It is not known why GBS infections have this age distribution which differs from that of invasive infections caused by other encapsulated bacteria. The aim of this study was to test the possibility that serum antibodies against the GBS capsular polysaccharides (CPS) are acquired during the first months of life thereby preventing infections after the neonatal period. Cord sera were collected from 321 healthy term newborns. A second blood sample was collected at 2, 4, 8, 13 or 26 weeks of age. IgG CPS antibodies (measured by ELISA) against serotypes Ia, II and III were present in 98%-100% of all cord sera and decreased continuously during the first 6 months of life. No IgM antibodies against serotype III CPS were present in cord sera. Only 16%-17% of the children acquired IgM antibodies against serotype III CPS at 3 and 6 months of age. CONCLUSION: Early acquisition of IgG or IgM antibodies against CPS of the most common GBS serotypes was not demonstrated and cannot explain the rare occurrence of invasive GBS infections in children after the 1st month of life.

Duchenne muscular dystrophy and spinal muscular atrophy type I segregating in the same family.

We report on a family with two severe neuromuscular diseases: Duchenne muscular dystrophy (DMD) and acute infantile spinal muscular atrophy (SMA I). One boy has DMD, and his brother died of SMA I at 11 months of age. Both boys had received the same DMD allele from their mother. Analysis of dystrophin by immunohistochemistry and Western blot showed complete lack of dystrophin in both brothers. The mother had a partial deficiency of dystrophin. The boy with SMA I had increased levels of creatine kinase in serum, compatible with DMD, but the muscle biopsy and post-mortem examination of the spinal cord showed the typical changes of SMA I. There were no cytogenetic abnormalities explaining the occurrence of both DMD and SMA I in this family. Molecular genetic prenatal diagnosis of DMD and SMA I, using analysis of RFLPs and dinucleotide repeats, has been performed in one foetus in the family. The results showed that the foetus had a high risk of developing SMA I. An abortion was planned but the pregnancy was terminated by miscarriage.

A comparison of ceftazidime and aminoglycoside based regimens as empirical treatment in 1316 cases of suspected sepsis in the newborn. European Society for Paediatric Infectious Diseases--Neonatal Sepsis Study Group.

We report a prospective, non-blind, randomised, multicentre, parallel group, multinational investigation to compare ceftazidime to aminoglycoside based regimens as empirical treatment in 1316 cases of suspected sepsis in the newborn. In each of the 15 study centres either ceftazidime alone (CAZ) or ceftazidime + ampicillin (CAZ + AMP) was compared to an amino-glycoside/ampicillin combination (AG + AMP). In all cases treatment was based on "an intention to treat". Bacteria considered to be pathogenic were isolated from 176/1316 (13.4%) patients. The incidence of proven infection varied from 39% in a Yugoslav centre to 6% in a British centre; a further 489/1316 (37.1%) patients fulfilled the criteria for clinically suspected sepsis. A total of 210 bacterial isolates from 197 infection sites in 176 patients were considered to be clinically significant. The cure rate for evaluable patients with proven infection who were treated with CAZ + AMP (97%, 30/31) was significantly higher than that for the corresponding patients treated with AG + AMP (66%, 26/39), (P < 0.002). The difference in cure rate between CAZ monotherapy (79%, 34/43) and AG + AMP (86%, 32/37) was not significant. Treatment failed in 28/150 (18.7%) evaluable patients. There were significantly fewer failures (P < 0.001) with CAZ + AMP than with AG + AMP therapy. There were 55 staphylococcal infections. Treatment was successful in 16/19 evaluable patients treated with CAZ or CAZ + AMP and in 16/29 evaluable patients treated with AG + AMP. None of the study centres encountered problems with ceftazidime resistant bacteria. The cure rate for patients with only clinical and radiological evidence of sepsis was greater than 94% in all treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampicillin-aminoglycoside combinations as initial treatment for neonatal septicaemia or meningitis. A retrospective evaluation of 12 years' experience.

In a retrospective study covering the years 1975-1986, 341 episodes of invasive infections in 338 newborn infants were evaluated. Of the 365 pathogens isolated from blood and/or cerebrospinal fluid, 91% were sensitive to either ampicillin or aminoglycosides or both. Ampicillin resistance was mainly found in very low and low birthweight infants with late-onset infections, in which aerobic Gram-negative rods were common pathogens. In contrast, aminoglycoside resistance was common in early-onset infections, due to the dominance of group B streptococcal infections. The ampicillin-aminoglycoside combination had been given as initial treatment in 189 cases of septicaemia or meningitis. Treatment failed in 36 infections (20%), although all organisms were sensitive to one or both antibiotics. Treatment failed in 6 of 34 patients with meningitis but the failure was not related to ampicillin or aminoglycoside resistance. In conclusion, both in vitro and clinical results show that the ampicillin-aminoglycoside combination can be used as initial treatment of invasive infections in neonates.

Incidence and etiology of neonatal septicaemia and meningitis in western Sweden 1975-1986.

In a retrospective study of neonatal septicaemia and meningitis in a defined region of western Sweden 1975-1986, 231 cases were identified. The incidence was 2.8/1000 live births. The case-fatality rate was 15%. thirty-three patients had meningitis. Only 55 patients (24%) had no known risk factors. Preterm delivery was a most important risk factor for both morbidity and mortality. The most common causative organisms were group B streptococci, Staphylococcus aureus and aerobic Gram-negative rods, together isolated from 82% of the patients. The cases were approximately equally divided between very early, early and late onset infections. Group B streptococci were over-represented in very early onset infections in all birthweight groups and aerobic Gram-negative rods were the most common isolates from low birthweight infants with late onset infections. However, group B streptococci, Staphylococcus aureus and Gram-negative rods were found in all birthweight and gestational age groups. Thus, initial antimicrobial therapy must be equally broad in all neonates with suspected septicaemia.

Incidence of early onset group B streptococcal septicemia in Sweden 1973 to 1985.

A retrospective investigation was made to determine the incidence of early onset group B streptococcal (GBS) septicemia in Sweden in relation to perinatal data. During the period 1973-1985 the yearly incidence of GBS septicemia increased from 0.1 to around 0.5 cases per 1,000 live births. In 416 cases verified by blood culture, the overall mortality was 15% 62/416). In babies with a birth weight of greater than 2,500 g this figure was 9.6% (29/303). In babies with a birth weight of less than 2,500 g the mortality was 29.2% (33/113). Males had a worse prognosis than females and were also more often affected. Thirty-six percent of the verified cases were premature, the gestational age being 36 weeks or less. An increased incidence among twins was also noted.

Concentrations of ceftazidime, tobramycin and ampicillin in the cerebrospinal fluid of newborn infants.

Thirty-five neonates with suspected septicaemia were randomized to treatment with tobramycin or ceftazidime, both in combination with ampicillin. Concentrations of antibiotics in the CSF were measured 1 h after the third, fourth or fifth injection. In 13 of 17 neonates tobramycin CSF concentrations were below 0.5 mg/l. Ceftazidime CSF concentrations ranged from 2.5 to 17 mg/l, which should be sufficient for treatment of infections with group B streptococci and most aerobic gram-negative bacilli but not all strains of Staphylococcus aureus. Ampicillin CSF concentrations ranged from 1 to 80 mg/l, which should be sufficient for treatment of meningitis caused by enterococci and Listeria monocytogenes, the most important neonatal pathogens not covered by ceftazidime.

Comparison of serum concentrations of ceftazidime and tobramycin in newborn infants.

Peak and trough serum concentrations of ceftazidime and tobramycin were determined in neonates with suspected septicaemia in an open randomized study. Mean peak serum levels were 85 (+/- 4.4 SE) mg/l for ceftazidime and 5.8 (+/- 0.3 SE) mg/l for tobramycin. The peak serum levels of ceftazidime were well above the reported minimal inhibitory concentration (MIC)90 values of pathogenic bacteria encountered in neonates, while peak serum levels of tobramycin were lower than reported MIC90 values for Klebsiella, Pseudomonas, Enterobacter and Serratia species. Nine of 33 tobramycin-treated patients had potentially toxic trough serum levels (greater than 2 mg/l) and nine had subtherapeutic peak serum levels (less than 4 mg/l). The dosage of this antibiotic had to be changed frequently. In comparison only 2 of 29 ceftazidime-treated patients had subtherapeutic peak levels (less than 40 mg/l) and none had potentially toxic trough levels (greater than 40 mg/l). Ceftazidime, in comparison with tobramycin, has a more favourable antibacterial spectrum and routine determinations of peak and trough serum levels should not be necessary.

Renal function of neonates during gentamicin treatment.

Thirteen newborn infants, 8 term and 5 preterm (gestational age 31 to 36 weeks), were treated for between 3 and 7 days with gentamicin and ampicillin or cloxacillin because of suspected bacterial infection. The dosage of gentamicin was carefully monitored by serum concentration assays. Urinary alanine aminopeptidase, urinary beta 2-microglobulin, serum urea, and serum beta 2-microglobulin were measured during and after the end of treatment to detect signs of renal toxicity. Levels of urinary aminopeptidase increased in 12 of them, indicating damage to the cells of the proximal tubuli. Changes in urinary beta 2-microglobulin followed the normal physiological course seen in neonates after birth. Serum levels of urea and beta 2-microglobulin did not indicate any drug-associated depression of glomerular filtration rate.