Neonatal serologic response at term to the genital mycoplasmas

Genital mycoplasmas are frequently found in the amniotic fluid (AF) of women with ruptured membranes but are infrequent pathogens in the neonates born to these women. The serologic response to the genital mycoplasmas, Mycoplasma hominis and Ureaplasma urealyticum, was studied in 35 mother-baby pairs following term deliveries. Amniotic fluid and neonatal surface cultures were obtained in all cases, as were maternal and neonatal acute and convalescent sera. Despite significant maternal serologic response, there was essentially no neonatal response. Mothers with M. hominis in the AF were significantly more likely than those with negative cultures for M. hominis to exhibit IgG seroconversion and had significantly greater changes in IgG concentrations. Their infants, however, did not exhibit a significant seroresponse regardless of the AF and neonatal culture results. There was also a significant maternal seroresponse to U. urealyticum. However, this did not correlate with the presence of U. urealyticum in the AF. Significantly fewer neonates exhibited a seroresponse to U. urealyticum, again with no relation to culture results.     

Vertical transmission of Ureaplasma urealyticum from mothers to preterm infants

Ureaplasma urealyticum is a common component of the vaginal flora during pregnancy. Although colonization of low birth weight infants with U. urealyticum occurs frequently, the actual rate of vertical transmission of U. urealyticum in preterm infants has not been determined. Sixty-five preterm infants (less than 37 weeks of gestation) born to mothers colonized with U. urealyticum had eye, throat, vagina and rectum cultured for U. urealyticum at 1, 3 and 7 days of age and weekly thereafter for the first month of life while the infants remained in the hospital. Thirty-eight infants (58%) had at least one culture site positive for U. urealyticum (eye, 8%; throat, 37%, vagina, 54%; and rectum, 18%). Vertical transmission was not affected by method of delivery or duration of rupture of amniotic membranes. The rate of vertical transmission of U. urealyticum was higher among infants with birth weight less than 1,000 g (89%) than among those with birth weight of 1,000 g or greater (54%) (P = 0.07). Chronic lung disease developed in 9 of the 65 (14%) infants; 8 were colonized with U. urealyticum. The high rate of ureaplasmal colonization and chronic lung disease in infants less than 1,000 g makes these infants a suitable target population for a clinical treatment trial to determine whether eradication of U. urealyticum would decrease the incidence of chronic lung disease.     

Mycoplasmal infections of cerebrospinal fluid in newborn infants from a community hospital population

Mycoplasma hominis or Ureaplasma urealyticum have previously been isolated from cerebrospinal fluid (CSF) in 13 of 100 newborn infants tested from a high risk university hospital population where the mothers were of predominantly lower income and socioeconomic status and had often received little or no prenatal care. We sought to determine whether such infections occur in neonates born to women cared for mainly through private obstetric practices and who delivered in 4 suburban community hospitals. CSF cultures were done in 318 infants during an 8-month period. M. hominis was isolated from 9 and U. urealyticum from 5 CSF cultures. Four infants infected with U. urealyticum and 3 infected with M. hominis were born at term. One infant infected with U. urealyticum had a birth weight of less than 1000 g. In 5 infants clearance of the infecting organism was documented without specific treatment. Twelve infants had good perinatal outcomes regardless of treatment and 2 died. One death in a 2240-g infant infected with M. hominis was associated with Haemophilus influenzae sepsis and pneumonia. The other death occurred 3 days after birth in a 630-g infant infected with U. urealyticum who had evidence of meningitis and intraventricular hemorrhage. Results of this study suggest that mycoplasmas are common causes of neonatal CSF infections, not only in high risk populations, but also in the general population.     

Ureaplasma urealyticum colonization of full term infants: perinatal acquisition and persistence during early infancy

In a prospective study 225 (35%) of 640 pregnant women who delivered at term had vaginal colonization with Ureaplasma urealyticum at the time of delivery. One hundred ninety-three full term infants born to U. urealyticum-colonized mother were cultured from the throat, eyes and vagina within the first 3 days of life. One hundred seven infants (55%) had at least one culture site positive for U. urealyticum (throat 41%, eyes 20%, vagina 40%). Rupture of membranes for greater than or equal to 12 hours and the mode of delivery did not affect vertical transmission of U. urealyticum. We were able to follow 108 infants during the first 3 months of life. Sixty-eight, 33 and 37% of the infants who were initially colonized with U. urealyticum in the throat, eyes and vagina, respectively, were still colonized when the follow-up cultures were obtained 3 months later. Fourteen of the 108 infants whom we followed developed a lower respiratory tract illness. In the pharyngeally colonized infants there was no increased risk for lower respiratory tract illness during early infancy compared with the pharyngeally noncolonized infants.     

Value and limits of research on Mycoplasma hominis and Ureaplasma urealyticum in the gastric fluid of newborn infants]

Mycoplasma hominis and Ureaplasma urealyticum were cultured and counted in the gastric fluid of 153 neonates divided into three groups: 28 preterm neonates managed in an intensive care unit (Group I); 83 full term neonates with suspected infection (Group II); and 42 full term neonates with no evidence of infection (Group III). The colonization rate (17.85%) in the intensive care unit group was not significantly different from the rates seen in the two other groups. These results do not militate against the pathogenic role of the two organisms studied but rather suggest a contributory role of other factors.     

Role of genital mycoplasmas in young infants with suspected sepsis

To establish the prevalence of Mycoplasma hominis and Ureaplasma urealyticum in infants up to 3 months of age with suspected sepsis, blood, cerebrospinal fluid, and urine specimens from 203 patients with clinical signs and symptoms of sepsis were cultured for Mycoplasma in addition to routine bacterial cultures. Proved bacterial infections were identified in 24 patients, four of whom had bacteremia. M. hominis and U. urealyticum were not isolated from any of the 191 blood and 199 CSF specimens tested. Of 170 specimens of urine cultured for Mycoplasma, M. hominis was isolated in six patients, U. urealyticum in nine patients, and both organisms in one patient. Twelve of the positive cultures were voided urine specimens, and four were suprapubic bladder aspiration specimens. Genital mycoplasmas appear to be uncommon causes of sepsis or meningitis in young infants. Further studies are required to assess their role in abnormal conditions of the urinary tract in childhood.     

Vertical transmission of Ureaplasma urealyticum in full term infants

Ureaplasma urealyticum is a common inhabitant of the urogenital tract of pregnant women. Although colonization of newborn infants with U. urealyticum has been documented previously, the actual rate of vertical transmission has not been determined. Cervical cultures for U. urealyticum were performed on 1315 pregnant women on admission to the labor suite. A positive culture was found in 810 (62%). Eye, nasopharyngeal and/or throat, vaginal and rectal cultures were obtained in the first 5 days of life from 132 full term infants born to mothers colonized with U. urealyticum. Fifty-nine infants (45%) had at least one culture site positive for U. urealyticum (eye, 4%; nasopharynx 24%; throat, 16%; vagina, 53%; and rectum, 9%). None of the infants had evidence of disease caused by U. urealyticum during the nursery stay. Vertical transmission was not affected by the method of delivery. However, among the vaginally delivered infants, rupture of membranes greater than 1 hour correlated with an increased rate of vertical transmission of U. urealyticum (52%) compared with rupture of membranes less than or equal to 1 hour (22%) (P less than 0.05). Because vertical transmission of U. urealyticum occurs frequently, caution must be exercised when attributing disease to U. urealyticum based solely on positive cultures of mucosal surfaces.     

Ureaplasma urealyticum and its association with chronic lung disease in Asian neonates

OBJECTIVE: The aim of the present prospective cohort study was to evaluate the relationship between lower respiratory tract colonization with Ureaplasma urealyticum and development of chronic lung disease (CLD) in a high-risk neonatal population. METHODS: Prospective cohort study of preterm infants with a birthweight < 1,500 g needing mechanical ventilation within 24 h of birth in a tertiary care neonatal unit. Endotracheal aspirates from these infants were cultured within 24 h for U. urealyticum and the rate of colonization was determined. The primary outcome measure was the incidence of CLD at 28 days of life. RESULTS: Of the 41 infants studied, 10 (24%) infants were colonized with U. urealyticum. The colonization rate was higher in babies < 1,000 g compared with babies weighing 1,000-1,500 g (P = 0.04). There was no significant difference between the colonized and non-colonized groups with regard to the antenatal use of steroids, maternal prolonged rupture of membranes, gestational age, birthweight, sex, respiratory distress syndrome, use of surfactant, patent ductus arteriosus and gastrooesophageal reflux. Of the 37 survivors, 20 (54%) developed CLD; eight infants (88.5%) in the colonized group developed CLD compared with 12 infants (42.8%) in the non-colonized group (P = 0.01). CONCLUSIONS: Neonates colonized with U. urealyticum were twice as likely to have CLD than non-colonized babies (relative risk 2.01; 95% confidence interval 1.27-3.37). These data suggest a significant association between colonization with U. urealyticum and CLD in infants weighing < 1,500 g.     

Determination of fetal infectious risk by bacteriological examination of the amniotic fluid after premature rupture of the membranes]

Amniotic fluid was obtained per vagina from 228 mothers with premature rupture of the membranes and examined bacteriologically. The aim was to assess the importance of amniotic fluid contamination and the risk of foetal infection in the absence of systematic antibiotic therapy in the mothers. The incidence of amniotic fluid contamination was apparently greater in those mothers who had received antibiotics although the proportion of neonates with a true infection (3%) was almost identical. The absence of selection of resistant organisms is indicated by the marked preponderance of streptococci and the scarcity of Gram negative enterobacteriacae. Thus it is reasonable not to give systemic antibiotics but to culture the amniotic fluid. Infection can then be anticipated and in affected neonates the appropriate therapy started immediately.     

Genital mycoplasmas in preterm infants: Prevalence and clinical significance

The genital mycoplasmas:Ureaplasma urealyticum andMycoplasma hominis have recently assumed an increasing importance as neonatal pathogens. The aim of the present survey was to determine the prevalence of infections with these organisms in preterm infants in two neonatal intensive care units in Israel. Among 99 preterm infants, 24 (24%) harboured mycoplasmas in their throats shortly after birth.U. urealyticum was the most common organism.M. hominis was isolated only from 3 infants. Six out of 27 (22%) mechanically ventilated infants secretedU. urealyticum in their lower airways. The rate of colonization was inversely correlated with gestational age; 80% of infants younger than 28 weeks gestation were found to be colonized as opposed to 17.9% at 28–36 weeks of gestation. No mycoplasmas were isolated in blood cultures drawn from 146 infants and CSF cultures obtained from 47 preterm infants. Neonatal mortality, respiratory complications and intraventricular haemorrhage grade 3–4 were significantly increased in colonized infants. However, above gestational age of 27 weeks, colonization with mycoplasmas was not associated with a worse prognosis. We conclude that colonization withU. urealyticum is common in Israeli preterm infants, correlates inversely with gestational age and has no detrimental effect on neonatal morbidity and mortality of infants older than 27 wks of gestation.     

Endotracheal colonization at birth is associated with a pathogen-dependent pro- and antiinflammatory cytokine response in ventilated preterm infants: a prospective cohort study

The possible association between mediators of inflammation such as cytokines and perinatal colonization of the respiratory tract remains unclear. This prospective cohort study evaluated endotracheal colonization in 141 ventilated preterm infants at birth. The relation with cytokine response in the airways and C-reactive protein (CRP) in umbilical blood was investigated. Of the 141 preterm infants enrolled in this study, 37 (26%) were colonized. In addition to traditional pathogens (61%), commensal species (26%) and Mycoplasmataceae (13%) were isolated. Both the pro-inflammatory cytokines IL-1 beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha as well as the antiinflammatory IL-10 are increased in colonized patients in a dose-dependent manner, with the strongest response in neonates colonized with Gram-negative organisms. There was no antimicrobial IL-12p70 response in colonized infants. Commensal flora is associated with the same inflammatory response as traditional pathogens. Although the umbilical cord blood CRP level was significantly higher in neonates with endotracheal colonization, it was highest in those colonized with Gram-negative organisms but still close to normal limits. Microorganisms in the endotracheal fluid of ventilated preterm infants are associated with a pathogen-specific and dose-dependent cytokine response in the airways and systemic CRP response.     

Colonization by Ureaplasma urealyticum and chronic lung disease in premature newborn infants under 32 weeks of gestation]

Colonization of the respiratory tract of premature newborn infants by genital mycoplasma is suspected to be associated with chronic lung disease. METHODS AND PATIENTS: We prospectively determined the prevalence of genital mycoplasma colonization with nasopharyngeal or endotracheal culture in preterm neonates younger than 32 weeks gestation and its possible association with the development of chronic lung disease in a prospective study. RESULTS: Fifty-nine infants were enrolled and 11 (19%) were colonized with Ureaplasma urealyticum. In the subgroup of 45 ventilated infants, seven of seven U. urealyticum-positive infants developed chronic pulmonary disease versus ten of 38 (26%) of U. urealyticum-negative infants (relative risk [RR] = 3.8; 95% confidence interval [CI] 2.2 to 6.5, P < 0.001). U. urealyticum-colonized infants had a lower median birth weight (760 vs 1,083 g, P = 0.04), a lower gestational age (26 vs 28 weeks, P = 0.03), and a higher incidence of symptomatic patent ductus arteriosus (P = 0.03). These potential confounding factors may partially explain the association between U. urealyticum and chronic pulmonary disease. However, this association remained statistically significant when the analysis was restricted to infants with birth weight of 1,000 g or less (RR = 2.3; 95% CI 1.3 to 4, P = 0.02) or to infants with a patent ductus arteriosus (RR = 2; 95% CI 1.3 to 3.1, P = 0.02). CONCLUSION: Colonization with U. urealyticum in ventilated preterm neonates younger than 32 weeks gestation is a significant risk factor of developing chronic pulmonary disease.     

Infection with Ureaplasma urealyticum and Mycoplasma hominis and the development of chronic lung disease in preterm infants

In a prospective cohort study in a tertiary referral neonatal intensive care unit, the endotracheal secretions of 40 consecutively intubated newborn infants, less than 31 weeks' gestation. were examined weekly for the genital mycoplasmas and all other common bacterial pathogens. Fifteen (37%) infants were positive for Ureaplasma urealyticum and/or Mycoplasma hominis. There were no differences in gestation, birthweight, use of surfactant, or time on ventilator between the culture-positive and negative babies. Thirteen (87%) of the culture-positive group developed chronic lung disease (CLD) compared with 11 (41%) of the negative group ( p = 0.0196). Of those culture-positive, 37% were not identified on the first specimen taken at the time of admission. These data suggest a significant association between infection with the urogenital mycoplasmas and CLD and also stress the need for repeated cultures to identify these organisms.     

Sexually transmissible infectious agents in sexually active and virginal asymptomatic adolescent girls

Sixty-eight sexually active and 52 virginal adolescent girls were evaluated for six sexually transmissible infectious agents: Gardnerella vaginalis, Ureaplasma urealyticum, Mycoplasma hominis, Chlamydia trachomatis, Trichomonas vaginalis, and Neisseria gonorrhoeae. There were significant differences between sexually active and virginal girls with respect to the prevalence of isolation of U urealyticum (75% v 33%, P less than .005), M hominis (27% v 10%, P less than .05), and C trachomatis (19% v 2%, P less than .025) but not for G vaginalis (34% v 17%, P = .09). N gonorrhoeae and T vaginalis were isolated exclusively from sexually active girls, but their low prevalence (6% and 9%, respectively) made the difference statistically insignificant (P = .2 and .06, respectively). Race, current v previous sexual activity, multiple sexual partners, oral contraceptive use, and concurrent isolation of another organism did not identify those at increased risk for chlamydial isolation. Such girls were significantly more likely to have inflammatory Papanicolaou smears (36% v 10%, P less than .05) and excessive WBC in their vaginal secretions (50% v 19%, P = .05). The data support the contention that C trachomatis, N gonorrhoeae, and T vaginalis are organisms that are predominantly acquired via sexual routes. Significant nonsexual modes of transmission are supported by the data for the genital mycoplasmas and G vaginalis. Finally, a history of sexual activity in an adolescent female warrants specific diagnostic testing for Chlamydia.     

Colonization of intestinal bacteria in ill neonates

Most previous studies have shown that the digestive tract of the neonate is rapidly and heavily colonized in the first few days of life, but all the studies so far used either feces or rectal swabs to isolate and identify bacterial colonization. The exact timing of intestinal colonization is not yet certain. From a retrospective analysis of 24 neonates with intestinal perforation and a prospective study of 30 ill neonates aged less than 10 days who recieved intestinal-tract operations, we found that the incidence of bacterial growth from small-and large-bowel specimens was significantly lower within 48 h after birth and the intestinal tract was almost completely sterile within 24 h after delivery. Most of the bacteria were aerobic gram-negative bacilli, and the most common species was Escherichia coli. Although our results may not represent conditions in the normal neonate, knowledge of bowel colonization in such patients will be helpful for further management. Accepted: 10 March 1998     

Neonatal escherichia coli infections: concerns regarding resistance to current therapy

Currently recommended antibiotic treatment of suspected neonatal sepsis is ampicillin and an aminoglycoside. Recently, we observed increasing ampicillin and gentamicin resistance in strains of Escherichia coli isolated from neonates at our institution. We therefore reviewed clinical and laboratory records of all neonates with systemic infection, hospitalized from 1994 through 1998, from whom E. coli was isolated from blood and/or cerebrospinal fluid. The influence of perinatal variables (e.g. rupture of foetal membranes > 24h, group B Streptococcus (GBS) colonization, urinary tract infection during pregnancy and the use of antepartum and/or intrapartum antibiotics), and neonatal variables (e.g. gestational age, age at onset of sepsis (early: < or = 72 h, late: >72 h), number of E. coli septic recurrences, and associated underlying medical and/or surgical conditions) on antimicrobial susceptibilities of invasive E. coli isolates was studied. Twenty-three neonates with invasive E. coli infection were identified; most [19 (83%)] presented as late-onset sepsis (LOS). Ampicillin-resistant E. coli were isolated in 75% and 53% of neonates in the early- and late-onset groups, respectively. Gentamicin resistance was found in 50% of early-onset sepsis (EOS) isolates compared with 16% in the late-onset group. Isolates from two neonates with EOS were resistant to both ampicillin and gentamicin. One neonate with EOS and three with LOS had recurrent E. coli sepsis; all isolates were ampicillin-resistant and one was gentamicin-resistant. All these neonates were initially treated with ampicillin and gentamicin. Both groups had associated underlying medical and/or surgical conditions (50% early-onset, 47% late-onset). Maternal GBS colonization occurred in 2 (50%) versus 3 (16%) of EOS and LOS cases, respectively. All GBS colonized women received intrapartum ampicillin prior to delivery. CONCLUSIONS: Ampicillin and gentamicin resistance is emerging in neonatal E. coli isolates from invasive infection. Current- empiric management of neonatal sepsis requires re-evaluation given changing antimicrobial susceptibilities.     

Routine use of fluconazole prophylaxis in a neonatal intensive care unit does not select natively fluconazole-resistant Candida subspecies

BACKGROUND: We have previously demonstrated efficacy against fungal colonization and infection of fluconazole prophylaxis that was routinely administered since 2001 in our ICU for preterm infants <1500 g at birth (VLBW). With prolonged use, concerns exist for the emergence of acquired fungal resistance and of Candida subspecies that are natively fluconazole-resistant (NFR), mostly Candida glabrata and Candida krusei. METHODS: We evaluated retrospectively all clinical and surveillance fungal isolates obtained from VLBW infants in our NICU during a 10-year period (1997-2006). Each fungal isolate was speciated, infants colonized or infected with NFR-Candida spp were identified and the incidence rates of colonization and infection by these fungal species were calculated. A comparison was made of the 6-year (2001-2006) prophylaxis period with the 4-year (1997-2000) preprophylaxis period. RESULTS: Overall, colonization by NFR-Candida spp ranged between 2.8% and 6.6% of VLBW infants yearly admitted, without any increasing trend during the study period. There were 18 of 434 (4.1%) neonates colonized by these species. Five episodes of systemic fungal infections caused by NFR-Candida spp occurred (incidence rate, 1.1%). No significant differences were detected when compared with the preprophylaxis period, when 11 of 295 infants (3.7%) were colonized by NFR-Candida spp and 4 episodes of infection occurred (1.4%) (P = 0.84 and 0.76, respectively). CONCLUSIONS: Fluconazole prophylaxis administered to VLBW neonates in 4- to 6-week courses after birth does not lead to the emergence of natively fluconazole-resistant Candida spp.     

Natural history of neonatal colonization with group B streptococci.

Thirteen percent of the newborns in our study group were colonized with group B streptococci on day 3. This colonization rate appeared constant during the first two weeks of life and then decreased to 5%. Of the babies colonized on day 3, 59% and 91% were culture-negative on days 14 and 42, respectively. Sixty-five percent of the babies carrying group B streptococci on day 14 acquired this microorganism following discharge (day 3). Babies colonized with staphylococci or Escherichia coli were found to have decreased probability of colonization with group B streptococci.     

Ureaplasma urealyticum, erythromycin and respiratory morbidity in high-risk preterm neonates

We investigated colonization with Ureaplasma urealyticum (Uu) in infants <30 weeks gestation and assessed the relationship to other risk factors influencing respiratory morbidity, plus the effect of treatment with erythromycin. Ventilated preterm infants [ n = 155; median GA 26 (23–29) weeks] were cultured for Uu in endotracheal aspirate and nasopharynx. Colonized infants were randomly assigned to treatment with erythromycin 40mg/kg/d, intravenously or orally. The rate of colonization was 29/155 (19%) and the Uu-colonized infants had lower mean gestational ages than the culture-negative infants (25 vs 26 weeks). For the colonized infants PROM (48% vs12%), chorioamnionitis in the mother (46% vs 17%) and vaginal delivery (71% vs 29%) were more common. More colonized infants needed supplemental oxygen at 36 weeks'postconceptual age ( p < 0:05). Erythromycin treatment was effective in reducing colonization with negative control cultures in 12/14 (86%) of treated infants. No significant differences were found between the colonized treated infants ( n = 14) and those not treated ( n = 14) in time with supplemental oxygen. Oxygen requirement at 36 weeks was related to lower gestational age, late appearance of PDA, late onset sepsis and signs of chorioamnionitis in the mother. We conclude that the Uu colonization is related to increasing immaturity, the presence of prolonged rupture of membranes, signs of chorioamnionitis and vaginal delivery. Treatment with erythromycin reduced colonization but did not significantly alter length of time with supplemental oxygen.     

Role of Ureaplasma urealyticum and other pathogens in the development of chronic lung disease of prematurity

A prospective cohort study enrolling 107 infants weighing less than 1250 g was conducted between September 1, 1986, and November 15, 1987 in order to determine the role of microorganisms on the development of chronic lung disease (CLD). Ureaplasma urealyticum was isolated significantly more frequently from gastric aspirates and nasopharyngeal or endotracheal aspirates from 43 infants developing CLD than from 56 who did not (51% vs. 16%; P less than 0.005). Infants developing CLD, defined by radiographic and blood gas abnormalities, were significantly younger (26 vs. 29 weeks; P less than 0.0001), weighed significantly less (830 vs. 1050 g; P less than 0.0001) and required more ventilatory support (37 vs. 10 were being ventilated and 42 vs. 26 received oxygen supplementation on Day 7) compared with those who did not develop CLD. Viruses were isolated in association with U. urealyticum in two infants developing CLD and in one infant who did not develop CLD. Mycoplasma hominis was isolated from three infants who were colonized with U. urealyticum and developed CLD. Chlamydia trachomatis was not recovered from any patients. From a discriminant analysis it was found that U. urealyticum contributed to the development of CLD along with the effect of ventilatory support, gestational age and severity of initial respiratory disease. The effect of interventions directed against U. urealyticum on the development of CLD deserves further study.