Acta Pa?diatr81: 788-91. 1992
Chlamydia trachomatis in neonatal respiratory distress of very preterm babies: biphasic clinical picture D Sollecito', M Midulla',2, M Bavastrelli2, A Panero2, G Marzetti3, D Rossi2, M Salzano2, M Roggini2 and G Bucci2 CNR Institute of Experimental Medicine'. Institute of Pediatrics "La Sapienza" University2, Department of Pediatrics Fatebenefralelli Hospital', Rome, Italy
Sollecito D, Midulla M, Bavastrelli M, Panero A, Marzetti G, Rossi D, Salzano M, Roggini M, Bucci G. Chlamydia trachomatis in neonatal respiratory distress of very preterm babies: biphasic clinical picture. Acta Pzediatr 1992;8 1:788-91. Stockholm. ISSN 0803-5253 We observed 12 very preterm infants (10 males) with a peculiar respiratory syndrome characterized by early onset soon after birth and by a biphasic course. The severe first phase was characterized by a clinical pattern mimicking the idiopathic respiratory distress syndrome of prematurity. Gradually, respiratory symptoms decreased and assisted ventilation with oxygen therapy was reduced. In the second phase, a significant worsening of respiratory signs and the appearance of apneic spells were observed. Chest X-ray showed hypoexpansion of the lungs and the prevalence of a fine reticular pattern. Chlamydia trachomatis was identified in this second phase in conjunctival and pharyngeal swabs and/or on tracheal aspirates. Our data suggest that in the very preterm infants, chlamydia] infection shows different clinical and laboratory features if compared with Chlamydia trachomatis pneumonia of infants born at term. 0 Biphasic clinical course, Chlamydia trachomatis, respiratory distress, very preterm infants M Midulla, Institute of Pediatrics "La Sapienza" University. V i d e Regina Elena 324,00161 Rome, Italy
Chlamydia trachomatis is a very diffuse pathogen in sexually active subjects and it may be transmitted from cervically infected women to their newborns at delivery. The prevalence of this infection in pregnant women (I) has been shown to vary from 2% to 47%. This wide range is due to dissimilar degrees of diffusion of C . trachomatis infection in different geographic areas and populations. C. trachomatis infects vaginally born infants from infected women, while in infants born after cesarean section, C. trachomatis infection is probably caused by an ascending chorion amnionitis (2-4). In term newborns, conjunctivitis is the most frequent picture (30-40%) of C. trachomatis infection. However, the more serious outcome of chlamydial infection in infants is interstitial pneumonia (5, 6). Chlamydia1 pneumonia, which occurs in 10-20% of exposed infants, is usually mild and sometimes afebrile (7,8). The clinical respiratory signs of chlamydia] pneumonia are tachypnea and cough (staccato paroxysms). The roentgenogram shows interstitial infiltrate and hyperexpansion. Eosinophilia and high levels of serum immunoglobulins are often present. Preliminary reports have suggested that chlamydia] pneumonia may have different features in low-birthweight neonates compared with mature babies (9). It is a more severe illness, sometimes fatal, that may require prolonged assisted ventilation and produce chronic
pulmonary symptoms (10- 1 3). We report our experience on infection with C. trachomatis in very preterm infants.
Patients and methods From August 1985 to October 1990 we investigated C . trachomatis infection in 37 newborn infants with respiratory distress showing atypical clinical and/or radiographic features. Particularly, we selected very preterm infants supplemented with oxygen at four weeks of age. All patients were cared for at the Neonatal Intensive Care Unit (NICU), Institute of Pediatrics "La Sapienza" University, Rome. In this unit preterm infants < 37 weeks gestation admitted during the study period numbered 352 and preterm infants < 3 2 weeks gestation 169. Conjunctival, pharyngeal swabs and/or tracheal aspirates were collected from the neonates: cervical, urethral, conjunctival and pharyngeal swabs were collected from the parents. The specimens were processed by two methods: (1) culture on McCoy monolayers treated with cycloheximide according to the method of Ripa & MArdh (14); after incubation for 48-72 h at 37"C, inoculated monolayers were stained with a modified Giemsa method and screened for typical inclusions by an optical microscope;
C. trachomatis in respiratory distress
ACTA PEDIATR 81 (1992)
789
Table 1. Clinical and laboratory findings in 12 very preterm babies with respiratory disease, infected by ChLamydia trachomatis.
Case
Sex
Gest. age (weeks)
Birth weight (9)
First chest X-ray
I
M
30
900
HMD
MV
24
2
M
30
1700
MV
23
3
M
30
1500
HMD PNX Normal
CPAP
27
4
M
27
1025
Normal
CPAP
38
5
F
29
1190
HE
CPAP
20
6
M
31
1910
MV
28
7
M
27
1170
Strands of radiodensity HE
8
M
25
780
MV
25 70
9
M
27
810
Strands of radiodensity HMD
MV
81
10
F
28
660
HMD
MV
25
I1
M
25
950
HMD
MV
46 80
12
M
24
950
HMD
MV
Respiratory treatment
C. trach. isolated (days)
18
50 104
Clinical picture Inspir. stridor, dyspnea, feed. prob. RDS I Tachypnea, feed. prob. Hypoxemia, tachypnea, feed. prob. Apneic spells, dyspnea, hypoxemia, EOS 17% Apneic spells, dyspnea Apneic spells tachypnea, abdom. dist., EOS 13% Apneic spells Apneic spells, CLD Apneic spells, high PaC02, abdom. dist., EOS 19Yu Apneic spells, EOS 28% Apneic spells
Last chest X-ray
0 2
Treat. efficacy
therapy (days)
Resp. outcome
HE
Yes
32
CE PNX HE
?
44
Yes
10
FRP
Yes
GGA DH
Yes
73
HE DH
Yes
13
HE DH
Yes
47
CLD
FRP
Yes
16
CLD
BDO
?
139
CLD
HE
Yes
45
HE RP
No
102
CLD
FRP
No
13
CLD PW
CLD
CLD
DE I
134
HMD = Hyaline membrane disease; PNX = pneumothorax; HE = hypoexpansion; MV = mechanical ventilation; CPAP=continuous positive airway pressure; EOS = eosinophils; Abdom. dist. =abdominal distension; CLD =chronic lung disease; CE =cystic emphysema; FRP = fine reticular pattern; GGA =ground glass appearance; DH =diffuse haziness; BDO =bilateral diffuse opacities; RP = reticular pattern; DE = diaphragmatic eventration; RDS = respiratory distress syndrome; I =impairment; PW =persistent wheezing.
(2) direct immunofluorescence (1 5) on freshly collected
specimens was performed adding 30 pl of a mixture of fluorescein-labeled monoclonal antibodies raised against the 15 serotypes of C. trachomatis (Microtrak, Syva); the test was considered positive if at least 10 typical fluorescing elementary bodies were seen under fluorescence microscope.
Results C. frachomatis was detected in 12 patients (10 males) with a gestational age between 24 and 31 weeks and birth weight of 660-1910 g (Table 1). Two infants (cases
1 and 12) were delivered by cesarean section because of maternal gestosis and one showed intact fetal membranes. In the other infants, the anamnesis of pregnancy regarding apparent causes of preterm delivery was negative. Cases 2 and 3 were twins. All patients presented respiratory distress at admission. The initial chest X-ray showed a picture mimicking hyaline membrane disease (HMD) in 6 of 12 infants, hypoexpansion in 4 of 12 infants, while in 2 of 12 infants chest X-ray was normal. Mechanical ventilation was established in 8 of 12 infants and lasted for 3-33 days (mean 1 1 & 9.7 days). Three babies required continuous positive airway
790
D Sollecito et al.
pressure (CPAP) by nasal prongs. One infant, transferred at 26 days of age from another unit, received only oxygen supplementation. All infants of 18-30 days of age showed a significant worsening of respiratory symptoms (8/12), with apneic spells resistant to specific treatment (8/12) and inspiratory stridor (1/12). Feeding problems (vomiting and abdominal distension) were also present in 5 of 12 infants. Significant eosinophilia (16-28%) was observed in 4 infants. Chest X-ray revealed lung hypoexpansion, hypotransparency and fine reticular pattern (10/12), bilateral opacifications (l/l2) and cystic interstitial emphysema with pneumothorax (l/l2). C. trachomatis was first identified at 18-81 days of age with both methods, in swabs and/or in tracheal aspirates, while cervical cultures were positive. for C. trachomatis in 6 of 9 mothers, and urethral cultures in 4 of 7 fathers examined. We obtained a second sample from the 12 infants one week after the end of therapy. Third samples were obtained a month after clinical improvement to assess eradication of C. trachomatis infection. Anti-infective chemotherapy (erythromycin ethylsuccinate, miokamycin) was given for 10-12 days. A second course of therapy with rifampicin was necessary in three patients (cases I , 11 and 12) because C. trachomatis was reisolated and erythromycin was not well tolerated. All patients survived. Chronic lung disease was evident in 7 patients but all were discharged. One patient was referred to a surgical department because of diaphragmatic eventration. One infant, still positive for C. trachomatis developed a persistent wheezing at 120 days of age. Table 1 summarizes the clinical and laboratory findings. We found a paradigmatic case of biphasic RDS in a very preterm baby with C. trachomatis infection. The boy (case 1) was born after 30 weeks gestation by cesarean section because of maternal gestosis. Fetal membranes were intact. The infant (900 g) was referred to the NICU soon after delivery because of RDS. Chest X-ray showed right-sided pneumothorax and subsequently bilateral hypoexpansion and diffuse granularity. The infant required mechanical ventilation for nine days. At 22 days of age he developed progressive respiratory difficulties with tachypnea, mild sternal and intercostal retractions, inspiratory stridor and diminuished air penetration in the lungs. Chest X-ray showed severe hypoexpansion: white blood count was 4600/mm3 with 3% eosinophils. C. trachomatis detected in the baby’s pharynx and conjunctiva, in the mother’s cervix and in the father’s urethra. The baby improved with oral erythromycin.
Discussion The infants in this study developed a peculiar respiratory syndrome characterized by an early onset after birth and a biphasic course. The isolation of C. trachomatis and the prompt response to specific antimicrobial
ACTA PKDIATR 81 (1992)
therapy, in most of the patients, are confirmation of a chlamydial etiology of late (second) phase of respiratory distress. A C. trachomatis infection may also contribute to the etiology of the first phase of respiratory disease, according to MArdh et al. (10) and Ushijima et al. (12). In very-low-birth-weight neonates, the respiratory syndrome, outlined by us, shows different features compared with chlamydial pneumonia in infants born at term. Our data indicate that preterm babies, apart from the respiratory symptoms and peculiar chest roentgenographic findings, showed some aspecific features, such as feeding problems and abdominal distension. Apnea could be a well recognized presentation of viral respiratory infection, particularly when it is caused by the respiratory syncytial virus, but generally it is not considered a respiratory sign presumptive of C. trachomatis infection. We stress, indeed, that apneic spells in preterm infants have to be considered a respiratory feature of C. trachomatis infection, as a high frequency was seen in these cases (8/12). Our data are in agreement with previous reports describing apneic spells in children and in preterm neonates with C. trachomatis (16-18) The peculiar radiographic findings were lung hypoexpansion and fine reticular pattern; we observed pulmonary hyperinflation only in case 2. Little information is available ( 1 9,20) concerning the incidence of C. trachomatis infection in mothers and newborns in Italy, while sufficient data are available for the USA (I). Therefore, it is very difficult to evaluate the incidence of this new respiratory syndrome that we observed. To prevent C. trachomatis infection in newborns, pregnant women should be examined for C. trachomatis and treated together with their partners with appropriate antibiotics. However, at the present time, screening for C. trachomatis is not performed routinely in Italian pregnant women. A search for C. trachomatis in the premature infant should be performed, as soon as possible, in all preterm infants attending a NICU, remembering that C. trachomatis can cause preterm deliveries. The duration of therapy is also important: previously recommended treatment was a 14-21-day course of macrolides with clinical improvement generally at 4 days after the start oftreatment (21). Three of our patients (cases I , 11, 12), treated with a short course of antibiotics (1-2 weeks), showed persistent positive cultures for C. trachomatis. In two, the clinical pattern did not improve. For this reason, antibiotic therapy should be prolonged for at least 3 weeks. Further search for C. trachomatis is necessary to check for eradication of the pathogen. Acknowledgements.-Supported by grant No. 9103613 from Progetto Finalizzato Prevenzione e Controllo dei Fattori di Malattia (FATMA) by the National Research Council (CNR)
References 1. Schachter J, Grossman M, Sweet RL, et al. Prospective study of
ACTA PADIATR R I (1992)
perinatal transmission of Chlamydia /rachomatis. JAMA 1986; 25513374-7 2. Givner LB, Rennels MB, Woodward CL, et al. Chlamydia frachomatis infection in infant delivered by caesarean section. Pediatrics 198 1 ;68:420- 1 3. La Scolea LJ, Parosky JS, Burzynsky L, et al. Chlamydia rrachomutis infection in infants delivered by caesarean section. Clin Pediatr 1984;23:118-20 4. Bell TA. Chlamydia fruchomatis infection in dizygotic twins delivered by caesarean section. Genitourin Med 1988;64:347-8 5. Schachter J, Lum L, Gooding G, et al. Pneumonitis following inclusion blenorrhea. J Pediatr 1975;87:779-80 6. Beem MO, Saxon EM. Respiratory-tract colonization and a distinctive pneumonia syndrome in infants delivered with Chlamydia trachomafir. N Engl J Med 1977;296:306-10 7. Rettig PJ. Perinatal infections with Chlamydia /rachoma/is. In: Freij BJ, Sever JL eds Infectious Complications of Pregnancy. Clinics in Perinatology. Philadelphia: WB Saunders, 1988: 15: 32 1-50 8. Tipple MA, Beem MO, Saxon EM. Clinical characteristic of the afebrile pneumonia associated with Chlamydia trachomatis infection in infants less than 6 months of age. Pediatrics 1979;63:192-7 9. Sollecito D, Panero A, Midulla M, et al. Prenatal Chlamydia trachomatis infection with postnatal respiratory disease in a preterm infant. Acta Paediatr Scand 1987;76:532 10. MBrdh P-A, Johansson PJH, Svenningsen N. Intrauterine lung infection with Chlamydia rrachornafis in a premature infant. Acta Paediatr Scand I984;73:569-72 11. Attenburrow AA, Barker CM. Chlamydia1 pneumonia in the low birthweight neonate. Arch Dis Child 1985;60:1169-72 12. Ushijima H, Hashira S, Shinozaki T, et al. Chlamydia trachomatis infection in a premature infant. Acta Paediatr Scand 1985;74:604
C. trachomatis in respiratory distress
791
13. Numazaki K, Chiba S, Kogawa K, et al. Chronic respiratory disease in premature infants caused by Chlamydia trachomaris. J Clin Pathol 1986;39:84-8 14. Ripa KT, MBrdh P-A. Cultivation of Chlamydia /rachoma/is in cycloheximide treated McCoy cells. J Clin Microbiol 1977;6: 328-3 I 15. Bell TA, Kuo CC, Stamm WE, et al. Direct fluorescent stain for rapid diagnosis of infants with Chlamjjdia /rachoma/is infection. Pediatrics I984;74224-7 16. Cohen SD. Azimi PH, Schachter J. Chlamydia trachomatis associated with severe rhinitis and apneic episodes in a month old infant. Clin Pediatr 1982;21:498-501 17. Zouari A, Dehan M, Magny JF, et al. Apnles revelatrices d’une infection a Chlamydia trachomaris chez un premature. Arch Fr Pediatr 1986;43:187-9 18. Brayden RM, Paisley JW, Lauer BA. Apnea in infants with Chlamydia frachomatis pneumonia. Pediatr Infect Dis J 1987; 4423-5 19. Sollecito D, Casadei AM, Piscione M, et al. Screening for Chlamydia rrachomutis infection in pregnant women and their newborns. XI European Congress of Perinatal Medicine, Rome, April 10-13 1988, 2nd volume. Rome: CIC Edizioni Internazionali, 1988:1059-63 20. Donati M, Cevenini R. Chlamydia trachomaris infections in Italy. 1 Proceedings of the European Society for Chlamydia Research, Bologna, May 30th-June 1st 1988. Bologna: Societa Editrice Esculapio, 1988:26 21. Beem MO, Saxon E, Tipple MA. Treatment of chlamydia1 pneumonia of infancy. Pediatrics 1979;63:198-203 Received July 27, 1991. Accepted Feb. 7, 1992
Chlamydia trachomatis in neonatal respiratory distress of very preterm babies: biphasic clinical picture D Sollecito', M Midulla',2, M Bavastrelli2, A Panero2, G Marzetti3, D Rossi2, M Salzano2, M Roggini2 and G Bucci2 CNR Institute of Experimental Medicine'. Institute of Pediatrics "La Sapienza" University2, Department of Pediatrics Fatebenefralelli Hospital', Rome, Italy
Sollecito D, Midulla M, Bavastrelli M, Panero A, Marzetti G, Rossi D, Salzano M, Roggini M, Bucci G. Chlamydia trachomatis in neonatal respiratory distress of very preterm babies: biphasic clinical picture. Acta Pzediatr 1992;8 1:788-91. Stockholm. ISSN 0803-5253 We observed 12 very preterm infants (10 males) with a peculiar respiratory syndrome characterized by early onset soon after birth and by a biphasic course. The severe first phase was characterized by a clinical pattern mimicking the idiopathic respiratory distress syndrome of prematurity. Gradually, respiratory symptoms decreased and assisted ventilation with oxygen therapy was reduced. In the second phase, a significant worsening of respiratory signs and the appearance of apneic spells were observed. Chest X-ray showed hypoexpansion of the lungs and the prevalence of a fine reticular pattern. Chlamydia trachomatis was identified in this second phase in conjunctival and pharyngeal swabs and/or on tracheal aspirates. Our data suggest that in the very preterm infants, chlamydia] infection shows different clinical and laboratory features if compared with Chlamydia trachomatis pneumonia of infants born at term. 0 Biphasic clinical course, Chlamydia trachomatis, respiratory distress, very preterm infants M Midulla, Institute of Pediatrics "La Sapienza" University. V i d e Regina Elena 324,00161 Rome, Italy
Chlamydia trachomatis is a very diffuse pathogen in sexually active subjects and it may be transmitted from cervically infected women to their newborns at delivery. The prevalence of this infection in pregnant women (I) has been shown to vary from 2% to 47%. This wide range is due to dissimilar degrees of diffusion of C . trachomatis infection in different geographic areas and populations. C. trachomatis infects vaginally born infants from infected women, while in infants born after cesarean section, C. trachomatis infection is probably caused by an ascending chorion amnionitis (2-4). In term newborns, conjunctivitis is the most frequent picture (30-40%) of C. trachomatis infection. However, the more serious outcome of chlamydial infection in infants is interstitial pneumonia (5, 6). Chlamydia1 pneumonia, which occurs in 10-20% of exposed infants, is usually mild and sometimes afebrile (7,8). The clinical respiratory signs of chlamydia] pneumonia are tachypnea and cough (staccato paroxysms). The roentgenogram shows interstitial infiltrate and hyperexpansion. Eosinophilia and high levels of serum immunoglobulins are often present. Preliminary reports have suggested that chlamydia] pneumonia may have different features in low-birthweight neonates compared with mature babies (9). It is a more severe illness, sometimes fatal, that may require prolonged assisted ventilation and produce chronic
pulmonary symptoms (10- 1 3). We report our experience on infection with C. trachomatis in very preterm infants.
Patients and methods From August 1985 to October 1990 we investigated C . trachomatis infection in 37 newborn infants with respiratory distress showing atypical clinical and/or radiographic features. Particularly, we selected very preterm infants supplemented with oxygen at four weeks of age. All patients were cared for at the Neonatal Intensive Care Unit (NICU), Institute of Pediatrics "La Sapienza" University, Rome. In this unit preterm infants < 37 weeks gestation admitted during the study period numbered 352 and preterm infants < 3 2 weeks gestation 169. Conjunctival, pharyngeal swabs and/or tracheal aspirates were collected from the neonates: cervical, urethral, conjunctival and pharyngeal swabs were collected from the parents. The specimens were processed by two methods: (1) culture on McCoy monolayers treated with cycloheximide according to the method of Ripa & MArdh (14); after incubation for 48-72 h at 37"C, inoculated monolayers were stained with a modified Giemsa method and screened for typical inclusions by an optical microscope;
C. trachomatis in respiratory distress
ACTA PEDIATR 81 (1992)
789
Table 1. Clinical and laboratory findings in 12 very preterm babies with respiratory disease, infected by ChLamydia trachomatis.
Case
Sex
Gest. age (weeks)
Birth weight (9)
First chest X-ray
I
M
30
900
HMD
MV
24
2
M
30
1700
MV
23
3
M
30
1500
HMD PNX Normal
CPAP
27
4
M
27
1025
Normal
CPAP
38
5
F
29
1190
HE
CPAP
20
6
M
31
1910
MV
28
7
M
27
1170
Strands of radiodensity HE
8
M
25
780
MV
25 70
9
M
27
810
Strands of radiodensity HMD
MV
81
10
F
28
660
HMD
MV
25
I1
M
25
950
HMD
MV
46 80
12
M
24
950
HMD
MV
Respiratory treatment
C. trach. isolated (days)
18
50 104
Clinical picture Inspir. stridor, dyspnea, feed. prob. RDS I Tachypnea, feed. prob. Hypoxemia, tachypnea, feed. prob. Apneic spells, dyspnea, hypoxemia, EOS 17% Apneic spells, dyspnea Apneic spells tachypnea, abdom. dist., EOS 13% Apneic spells Apneic spells, CLD Apneic spells, high PaC02, abdom. dist., EOS 19Yu Apneic spells, EOS 28% Apneic spells
Last chest X-ray
0 2
Treat. efficacy
therapy (days)
Resp. outcome
HE
Yes
32
CE PNX HE
?
44
Yes
10
FRP
Yes
GGA DH
Yes
73
HE DH
Yes
13
HE DH
Yes
47
CLD
FRP
Yes
16
CLD
BDO
?
139
CLD
HE
Yes
45
HE RP
No
102
CLD
FRP
No
13
CLD PW
CLD
CLD
DE I
134
HMD = Hyaline membrane disease; PNX = pneumothorax; HE = hypoexpansion; MV = mechanical ventilation; CPAP=continuous positive airway pressure; EOS = eosinophils; Abdom. dist. =abdominal distension; CLD =chronic lung disease; CE =cystic emphysema; FRP = fine reticular pattern; GGA =ground glass appearance; DH =diffuse haziness; BDO =bilateral diffuse opacities; RP = reticular pattern; DE = diaphragmatic eventration; RDS = respiratory distress syndrome; I =impairment; PW =persistent wheezing.
(2) direct immunofluorescence (1 5) on freshly collected
specimens was performed adding 30 pl of a mixture of fluorescein-labeled monoclonal antibodies raised against the 15 serotypes of C. trachomatis (Microtrak, Syva); the test was considered positive if at least 10 typical fluorescing elementary bodies were seen under fluorescence microscope.
Results C. frachomatis was detected in 12 patients (10 males) with a gestational age between 24 and 31 weeks and birth weight of 660-1910 g (Table 1). Two infants (cases
1 and 12) were delivered by cesarean section because of maternal gestosis and one showed intact fetal membranes. In the other infants, the anamnesis of pregnancy regarding apparent causes of preterm delivery was negative. Cases 2 and 3 were twins. All patients presented respiratory distress at admission. The initial chest X-ray showed a picture mimicking hyaline membrane disease (HMD) in 6 of 12 infants, hypoexpansion in 4 of 12 infants, while in 2 of 12 infants chest X-ray was normal. Mechanical ventilation was established in 8 of 12 infants and lasted for 3-33 days (mean 1 1 & 9.7 days). Three babies required continuous positive airway
790
D Sollecito et al.
pressure (CPAP) by nasal prongs. One infant, transferred at 26 days of age from another unit, received only oxygen supplementation. All infants of 18-30 days of age showed a significant worsening of respiratory symptoms (8/12), with apneic spells resistant to specific treatment (8/12) and inspiratory stridor (1/12). Feeding problems (vomiting and abdominal distension) were also present in 5 of 12 infants. Significant eosinophilia (16-28%) was observed in 4 infants. Chest X-ray revealed lung hypoexpansion, hypotransparency and fine reticular pattern (10/12), bilateral opacifications (l/l2) and cystic interstitial emphysema with pneumothorax (l/l2). C. trachomatis was first identified at 18-81 days of age with both methods, in swabs and/or in tracheal aspirates, while cervical cultures were positive. for C. trachomatis in 6 of 9 mothers, and urethral cultures in 4 of 7 fathers examined. We obtained a second sample from the 12 infants one week after the end of therapy. Third samples were obtained a month after clinical improvement to assess eradication of C. trachomatis infection. Anti-infective chemotherapy (erythromycin ethylsuccinate, miokamycin) was given for 10-12 days. A second course of therapy with rifampicin was necessary in three patients (cases I , 11 and 12) because C. trachomatis was reisolated and erythromycin was not well tolerated. All patients survived. Chronic lung disease was evident in 7 patients but all were discharged. One patient was referred to a surgical department because of diaphragmatic eventration. One infant, still positive for C. trachomatis developed a persistent wheezing at 120 days of age. Table 1 summarizes the clinical and laboratory findings. We found a paradigmatic case of biphasic RDS in a very preterm baby with C. trachomatis infection. The boy (case 1) was born after 30 weeks gestation by cesarean section because of maternal gestosis. Fetal membranes were intact. The infant (900 g) was referred to the NICU soon after delivery because of RDS. Chest X-ray showed right-sided pneumothorax and subsequently bilateral hypoexpansion and diffuse granularity. The infant required mechanical ventilation for nine days. At 22 days of age he developed progressive respiratory difficulties with tachypnea, mild sternal and intercostal retractions, inspiratory stridor and diminuished air penetration in the lungs. Chest X-ray showed severe hypoexpansion: white blood count was 4600/mm3 with 3% eosinophils. C. trachomatis detected in the baby’s pharynx and conjunctiva, in the mother’s cervix and in the father’s urethra. The baby improved with oral erythromycin.
Discussion The infants in this study developed a peculiar respiratory syndrome characterized by an early onset after birth and a biphasic course. The isolation of C. trachomatis and the prompt response to specific antimicrobial
ACTA PKDIATR 81 (1992)
therapy, in most of the patients, are confirmation of a chlamydial etiology of late (second) phase of respiratory distress. A C. trachomatis infection may also contribute to the etiology of the first phase of respiratory disease, according to MArdh et al. (10) and Ushijima et al. (12). In very-low-birth-weight neonates, the respiratory syndrome, outlined by us, shows different features compared with chlamydial pneumonia in infants born at term. Our data indicate that preterm babies, apart from the respiratory symptoms and peculiar chest roentgenographic findings, showed some aspecific features, such as feeding problems and abdominal distension. Apnea could be a well recognized presentation of viral respiratory infection, particularly when it is caused by the respiratory syncytial virus, but generally it is not considered a respiratory sign presumptive of C. trachomatis infection. We stress, indeed, that apneic spells in preterm infants have to be considered a respiratory feature of C. trachomatis infection, as a high frequency was seen in these cases (8/12). Our data are in agreement with previous reports describing apneic spells in children and in preterm neonates with C. trachomatis (16-18) The peculiar radiographic findings were lung hypoexpansion and fine reticular pattern; we observed pulmonary hyperinflation only in case 2. Little information is available ( 1 9,20) concerning the incidence of C. trachomatis infection in mothers and newborns in Italy, while sufficient data are available for the USA (I). Therefore, it is very difficult to evaluate the incidence of this new respiratory syndrome that we observed. To prevent C. trachomatis infection in newborns, pregnant women should be examined for C. trachomatis and treated together with their partners with appropriate antibiotics. However, at the present time, screening for C. trachomatis is not performed routinely in Italian pregnant women. A search for C. trachomatis in the premature infant should be performed, as soon as possible, in all preterm infants attending a NICU, remembering that C. trachomatis can cause preterm deliveries. The duration of therapy is also important: previously recommended treatment was a 14-21-day course of macrolides with clinical improvement generally at 4 days after the start oftreatment (21). Three of our patients (cases I , 11, 12), treated with a short course of antibiotics (1-2 weeks), showed persistent positive cultures for C. trachomatis. In two, the clinical pattern did not improve. For this reason, antibiotic therapy should be prolonged for at least 3 weeks. Further search for C. trachomatis is necessary to check for eradication of the pathogen. Acknowledgements.-Supported by grant No. 9103613 from Progetto Finalizzato Prevenzione e Controllo dei Fattori di Malattia (FATMA) by the National Research Council (CNR)
References 1. Schachter J, Grossman M, Sweet RL, et al. Prospective study of
ACTA PADIATR R I (1992)
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