Acute Hypoxemic Respiratory Failure Caused by Chlamydia trachomatis and Diagnosed by Flexible Bronchoscopy1.2
WILLIAM B. WHEELER, STEPHEN C. KURACHEK, JEFFREY G. LOBAS, and MITCHELL J. EINZIG Introduction Chlamydia trachomatis pneumonia in infants is typically characterized by staccato cough, bilateral interstitial infiltrates on the chest radiograph, wheezing, crackles, and tachypnea (1). Most infants are afebrile, and many have concurrent conjunctivitis (2). The usual clinical course is benign, and the patients respond well to antibiotic therapy (3). We herein present a case of Chlamydia trachomatis pneumonia that is unusual because of its severity and its radiographic presentation. This case was diagnosed by bronchoalveolar lavage using techniques similar to those described by McKenzie and coworkers (4) and Leigh and colleagues (5). Case Report A 2-wk-old female mulatto was admitted to Minneapolis Children's Medical Center after a two-day history of paroxysmal cough and tachypnea. On the day of admission, she had decreased oral intake, but no fever. The initial chest radiograph showed diffuse parenchymal infiltrates with a reticulonodular appearance and alveolar filling on the right. Hyperinflation was present (figure 1). The CBC with differential revealed a hematocrit of 40.3, a hemoglobin of 13.5, and a white blood cell count of 35,300 with a left shift. Physical examination revealed a markedly tachypneic infant: pulse, 150; respiratory rate, 98; blood pressure, 74/61; weight, 3.l5 kg. Oxygen saturations were 600/0 in room air, but increased to 95% on 70% oxygen by oxyhood. Arterial blood gas determination in room air showed: pH, 7.35; Po., 28; Peo., 55; bicarbonate, 31; O. saturation, 48%. Because of severe oxygen desaturation with coughing or agitation, the patient was pretreated with fentanyl and atropine, and paralyzed with atracurium. Flexible bronchoscopy was performed via a modified Mapleson anesthesia circuit. An adaptor (Instrumentation Industries, Bethel Park, PA) was placed between the bag and the mask so that the flexible bronchoscope (BF 3CIO; Olympus Corp. of America, New Hyde Park, NY) could be advanced through the left nostril and the glottic opening intubated. The bronchoscope was advanced into the distal trachea, and the mainstem bronchi were examined. The patient's O. saturations were maintained above 85% with controlled ventilation around the bronchoscope. The scope was introduced into the right upper lobe bronchus, and 10 ml of saline was lavaged with a 5-ml return. The right middle lobe was also lavaged with a 3-ml return. These secretions were sent for appropriate smears and cultures. The bronchoscopy was terminated after finding only mild edema of the airways with some mucoid secretions but no anatomic obstructive lesions or signs of pulmonary alveolar hemorrhage. The patient was nasally intubated and ventilated. Dynamic compliance was 0.8 mllcm H.O/kg (normal range> 2.0). Arterial blood gas determinations during an FlO. of 1.0 and a PEEP of 10 cm HlO showed: pH, 7.40; Po., 67; Peol , 40; biAM REV RESPIR DIS 1990; 142:471-473
carbonate, 25; O. saturation, 92%. An echocardiogram was normal. Direct immunofluorescent studies on the bronchoalveolar lavage (BAL) washings were negative for pertussis, respiratory syncytial virus, and cytomegalovirus, but positive for Chlamydia trachomatis (MicroTrak; Syva, Palo Alto, CA). Histologic examination of the bronchial washings revealed a marked inflammatory response, with neutrophils, macrophages, and lymphocytes. Neutrophils were the predominant cell, and histiocytes and eosinophils were not present. Inclusion bodies and multinucleated giant cells were not present. Fungal and PAS stains were negative. Cultures for fungus, Nocardia, Ureaplasma, viruses, pertussis, and aerobic and anaerobic bacteria were negative. After 48 h, cultures for Chlamydia trachomatis were strongly positive. The patient was initially treated with ampicillin and cefotaxime because of concern about bacterial pneumonia. Erythromycin was added within 24 h to cover Chlamydia trachomatis and Ureaplasma based on the BAL results. The patient required prolonged ventilatory support for the next 10 days, and mUltiple ventilator maneuvers were performed to increase oxygenation status. After a marked diuresis and 3 days of erythromycin, the patient began to wean from full ventilation. The patient steadily improved over the next 7 days and was extubated after 10 days of mechanical ventilatory support. The serum IgM was 362 mg/dl (normal, zero to 25) on admission. Serum IgG was not obtained. Specific antichlamydia antibody titers were assessed by a microimmunofluorescent test, with IgG of 1:128 and IgM greater than 1:256. Convalescent serum samples were not obtained. The patient had an uneventful recovery postextubation and was weaned from oxygen 2 wk after admission. The patient was ultimately treated with erythromycin 50 mg/kg/day for 21 days. During the convalescent phase, the mother developed acute cervicitis, and Chlamydia was cultured from her genitourinary tract. She was also treated with erythromycin and responded rapidly. At 6 months of age, the infant is thriving, with a clear chest radiograph, a normal physical examination, and an oxygen saturation of 98%.
Discussion Infants with Chlamydia trachomatis pneumonitis usually present with afebrile tachypnea, diffuse interstitial infiltrates on chest radiograph, crackles, wheezes, and conjunctivitis. It is extremely rare for these patients to develop respiratory failure. Brasfield and coworkers (6) found only one of 61 patients with Chlamydia trachomatis pneumonitis to require mechanical ventilatory support. The type of respiratory failure was not characterized, however. Klingebiel and colleagues (7) recently described a case of severe Chlamydia trachomatis pneumonia in a 4-month-old in-
fant who presented with a pneumothorax and severe hypoxemia. This child was ultimately found to have an IgO subclass deficiency, and required intensive care and mechanical ventilatory support for 5 wk. The chest radiograph in this infant was clearly unusual compared with prior reported cases. Radkowski and coworkers (8) have reviewed the chest radiographs of 125 cases of Chlamydia trachomatis pneumonia in young infants. In their study, no patient had evidence of pleural effusion or lobar consolidation. All patients had signs of bilateral lung involvement, but only three of the patients had bilateral alveolar infiltrates as seen in this case. The clinical course of these patients was not described, so it is unclear whether the patients with more severe radiographic findings had a more severe clinical course. Our case certainly illustrates the extensive radiographic changes that may occur with Chlamydia pneumonia, a feature also suggested by Lebel and colleagues (9). The severe clinical illness and mortality associated with Chlamydia trachomatis pneumonia is poorly appreciated by the pediatric community. Datta and coworkers (10) have documented the morbidity associated with Chlamydia trachomatis infection, and have observed that mortality can occur. Brasfield and coworkers (6) have also reported mortality associated with Chlamydia trachomatis infection, but it is unclear that the death of their patient was related to pneumonia. Long-term morbidity, however, was very significant in this population with infantile pneumonia. Many of these patients exhibited recurrent wheezing, persistent radiographic abnormalities, and abnormal pulmonary function studies months to years after the initial infection. Unfortunately, these investigators did not correlate long-term outcome with the initial infective agent.
(Received in original form January 23, 1990 and in revised form April 2. 1990) 1 From the Division of Pediatric Pulmonology and Critical Care Medicine, Minneapolis Children's Medical Center, and the University of Minnesota, Department of Pediatrics, Minneapolis, Minnesota. • Correspondence and requests for reprints should be addressed to William B. Wheeler, M.D., Children's Respiratory and Critical Care Specialists, P.A., 910 Medical Place, Suite 130, Minneapolis, MN 55404.
471
472
CASE REPORT
An interesting feature of this case is that the diagnosis was made by direct inspection of the airway and BAL. Not only were the washings positive for Chlamydia trachomatis on immunofluorescent antibody staining and culture, but negative findings on appropriate smears were very helpful in defining initial antibiotic therapy. The technique of flexible bronchoscopy with bag and mask ventilation after paralysis is a standard technique in our institution for hypoxemic, critically ill infants who cannot tolerate the procedure during spontaneous ventilation. However, this should not be undertaken by physicians unskilled in airway support and pediatric bronchoscopy. This procedure can be carried out in critically ill children in a safe fashion, and very helpful diagnostic data can be derived from the procedure. To our knowledge, this is the first reported case of infantile Chlamydia trachomatispneumonitis diagnosed by BAL. In young infants presenting with diffuse pulmonary infiltrates and respiratory failure, the diagnosis of Chlamydia trachomatis should be entertained and ruled out by appropriate studies, including bronchoscopy and BAL. BAL fluid should be sent for rapid immunofluorescent antibody staining studies. Aggressive supportive and antimicrobial therapy may result in complete recovery from the initial insult. Parents of any infant with Chlamydia trachomatis infection should be evaluated and treated for occult infection to prevent progressive chlamydial genitourinary disease. Long-term follow-up should be provided these infants to assess their propensity to reactive airway disease and chronic obstructive lung disease.
Acknowledgment The writers thank Dr. Julius Schachter for performing the specific antichlamydia antibody titers on this patient's serum.
References
Fig. 1. Preintubation and postintubation radiographs showing bilateral interstitial and alveolar disease from Chlamydia traehomatis. Improvement in lung volumes is seen after bronehoalveolar lavage with PEEP of 10 em H,O.
1. Tipple MA, Beem MO, Saxon EM. Clinical characteristics of the afebrile pneumonia associated with Chlamydia trachomatis infection in infants less than six months of age. Pediatrics 1979; 63: 192-7. 2. Preece PM, Anderson JM, Thompson RO. Chlamydia trachomatis infection in infants: a prospective study. Arch Dis Child 1989; 64:525-9. 3. Beem MO, Saxon EM, Tipple MA. Treatment of Chlamydia pneumonia of infancy. Pediatrics 1979; 63:198-203. 4. McKenzie B, Wood RE, Bailey A. Airway management for unilateral lung lavage in children. Anesthesiology 1989; 70:550-3. 5. Leigh MW, Henshaw NO, Wood RE. Diagnosis of Pneumocystis carinii pneumonia in pediatric patients using bronchoscopic bronchoalveolar lavage. Pediatr Infect Dis 1985; 4:408-10. 6. Brasfield OM, Stagno S, Whitley RJ, et al. Infant pneumonitis associated with cytomegalovirus, Chlamydia, Pneumocystis, and Ureaplasma: followup. Pediatrics 1987; 79:76-83.
473
CASE REPORT
7. Klingebiel T, Pickert A, Dopfer R, et al. Unusual course of a Chlamydia pneumonia in an infant with IgG/IgG4 deficiency. Eur J Pediatr 1989; 148:431-4. 8. Radkowski MA, Kranzler JK, Beem MO, Tip-
pie MA. Chlamydia pneumonia in infants: radiography in 125 cases. AJR 1981; 137:703-6. 9. Lebel MH, Lamarre A, Rosseau E. Pneumothorax: new manifestation of Chlamydia trachomatis infection in infancy. Pediatr Pulmonol 1987; 3:
362-3. 10. Datta P, Laga M, Plummer FA, et al. Infection and disease after perinatal exposure to Chlamydia trachomatis in Nairobi, Kenya. J Infect Dis 1988; 158:524-8.
WILLIAM B. WHEELER, STEPHEN C. KURACHEK, JEFFREY G. LOBAS, and MITCHELL J. EINZIG Introduction Chlamydia trachomatis pneumonia in infants is typically characterized by staccato cough, bilateral interstitial infiltrates on the chest radiograph, wheezing, crackles, and tachypnea (1). Most infants are afebrile, and many have concurrent conjunctivitis (2). The usual clinical course is benign, and the patients respond well to antibiotic therapy (3). We herein present a case of Chlamydia trachomatis pneumonia that is unusual because of its severity and its radiographic presentation. This case was diagnosed by bronchoalveolar lavage using techniques similar to those described by McKenzie and coworkers (4) and Leigh and colleagues (5). Case Report A 2-wk-old female mulatto was admitted to Minneapolis Children's Medical Center after a two-day history of paroxysmal cough and tachypnea. On the day of admission, she had decreased oral intake, but no fever. The initial chest radiograph showed diffuse parenchymal infiltrates with a reticulonodular appearance and alveolar filling on the right. Hyperinflation was present (figure 1). The CBC with differential revealed a hematocrit of 40.3, a hemoglobin of 13.5, and a white blood cell count of 35,300 with a left shift. Physical examination revealed a markedly tachypneic infant: pulse, 150; respiratory rate, 98; blood pressure, 74/61; weight, 3.l5 kg. Oxygen saturations were 600/0 in room air, but increased to 95% on 70% oxygen by oxyhood. Arterial blood gas determination in room air showed: pH, 7.35; Po., 28; Peo., 55; bicarbonate, 31; O. saturation, 48%. Because of severe oxygen desaturation with coughing or agitation, the patient was pretreated with fentanyl and atropine, and paralyzed with atracurium. Flexible bronchoscopy was performed via a modified Mapleson anesthesia circuit. An adaptor (Instrumentation Industries, Bethel Park, PA) was placed between the bag and the mask so that the flexible bronchoscope (BF 3CIO; Olympus Corp. of America, New Hyde Park, NY) could be advanced through the left nostril and the glottic opening intubated. The bronchoscope was advanced into the distal trachea, and the mainstem bronchi were examined. The patient's O. saturations were maintained above 85% with controlled ventilation around the bronchoscope. The scope was introduced into the right upper lobe bronchus, and 10 ml of saline was lavaged with a 5-ml return. The right middle lobe was also lavaged with a 3-ml return. These secretions were sent for appropriate smears and cultures. The bronchoscopy was terminated after finding only mild edema of the airways with some mucoid secretions but no anatomic obstructive lesions or signs of pulmonary alveolar hemorrhage. The patient was nasally intubated and ventilated. Dynamic compliance was 0.8 mllcm H.O/kg (normal range> 2.0). Arterial blood gas determinations during an FlO. of 1.0 and a PEEP of 10 cm HlO showed: pH, 7.40; Po., 67; Peol , 40; biAM REV RESPIR DIS 1990; 142:471-473
carbonate, 25; O. saturation, 92%. An echocardiogram was normal. Direct immunofluorescent studies on the bronchoalveolar lavage (BAL) washings were negative for pertussis, respiratory syncytial virus, and cytomegalovirus, but positive for Chlamydia trachomatis (MicroTrak; Syva, Palo Alto, CA). Histologic examination of the bronchial washings revealed a marked inflammatory response, with neutrophils, macrophages, and lymphocytes. Neutrophils were the predominant cell, and histiocytes and eosinophils were not present. Inclusion bodies and multinucleated giant cells were not present. Fungal and PAS stains were negative. Cultures for fungus, Nocardia, Ureaplasma, viruses, pertussis, and aerobic and anaerobic bacteria were negative. After 48 h, cultures for Chlamydia trachomatis were strongly positive. The patient was initially treated with ampicillin and cefotaxime because of concern about bacterial pneumonia. Erythromycin was added within 24 h to cover Chlamydia trachomatis and Ureaplasma based on the BAL results. The patient required prolonged ventilatory support for the next 10 days, and mUltiple ventilator maneuvers were performed to increase oxygenation status. After a marked diuresis and 3 days of erythromycin, the patient began to wean from full ventilation. The patient steadily improved over the next 7 days and was extubated after 10 days of mechanical ventilatory support. The serum IgM was 362 mg/dl (normal, zero to 25) on admission. Serum IgG was not obtained. Specific antichlamydia antibody titers were assessed by a microimmunofluorescent test, with IgG of 1:128 and IgM greater than 1:256. Convalescent serum samples were not obtained. The patient had an uneventful recovery postextubation and was weaned from oxygen 2 wk after admission. The patient was ultimately treated with erythromycin 50 mg/kg/day for 21 days. During the convalescent phase, the mother developed acute cervicitis, and Chlamydia was cultured from her genitourinary tract. She was also treated with erythromycin and responded rapidly. At 6 months of age, the infant is thriving, with a clear chest radiograph, a normal physical examination, and an oxygen saturation of 98%.
Discussion Infants with Chlamydia trachomatis pneumonitis usually present with afebrile tachypnea, diffuse interstitial infiltrates on chest radiograph, crackles, wheezes, and conjunctivitis. It is extremely rare for these patients to develop respiratory failure. Brasfield and coworkers (6) found only one of 61 patients with Chlamydia trachomatis pneumonitis to require mechanical ventilatory support. The type of respiratory failure was not characterized, however. Klingebiel and colleagues (7) recently described a case of severe Chlamydia trachomatis pneumonia in a 4-month-old in-
fant who presented with a pneumothorax and severe hypoxemia. This child was ultimately found to have an IgO subclass deficiency, and required intensive care and mechanical ventilatory support for 5 wk. The chest radiograph in this infant was clearly unusual compared with prior reported cases. Radkowski and coworkers (8) have reviewed the chest radiographs of 125 cases of Chlamydia trachomatis pneumonia in young infants. In their study, no patient had evidence of pleural effusion or lobar consolidation. All patients had signs of bilateral lung involvement, but only three of the patients had bilateral alveolar infiltrates as seen in this case. The clinical course of these patients was not described, so it is unclear whether the patients with more severe radiographic findings had a more severe clinical course. Our case certainly illustrates the extensive radiographic changes that may occur with Chlamydia pneumonia, a feature also suggested by Lebel and colleagues (9). The severe clinical illness and mortality associated with Chlamydia trachomatis pneumonia is poorly appreciated by the pediatric community. Datta and coworkers (10) have documented the morbidity associated with Chlamydia trachomatis infection, and have observed that mortality can occur. Brasfield and coworkers (6) have also reported mortality associated with Chlamydia trachomatis infection, but it is unclear that the death of their patient was related to pneumonia. Long-term morbidity, however, was very significant in this population with infantile pneumonia. Many of these patients exhibited recurrent wheezing, persistent radiographic abnormalities, and abnormal pulmonary function studies months to years after the initial infection. Unfortunately, these investigators did not correlate long-term outcome with the initial infective agent.
(Received in original form January 23, 1990 and in revised form April 2. 1990) 1 From the Division of Pediatric Pulmonology and Critical Care Medicine, Minneapolis Children's Medical Center, and the University of Minnesota, Department of Pediatrics, Minneapolis, Minnesota. • Correspondence and requests for reprints should be addressed to William B. Wheeler, M.D., Children's Respiratory and Critical Care Specialists, P.A., 910 Medical Place, Suite 130, Minneapolis, MN 55404.
471
472
CASE REPORT
An interesting feature of this case is that the diagnosis was made by direct inspection of the airway and BAL. Not only were the washings positive for Chlamydia trachomatis on immunofluorescent antibody staining and culture, but negative findings on appropriate smears were very helpful in defining initial antibiotic therapy. The technique of flexible bronchoscopy with bag and mask ventilation after paralysis is a standard technique in our institution for hypoxemic, critically ill infants who cannot tolerate the procedure during spontaneous ventilation. However, this should not be undertaken by physicians unskilled in airway support and pediatric bronchoscopy. This procedure can be carried out in critically ill children in a safe fashion, and very helpful diagnostic data can be derived from the procedure. To our knowledge, this is the first reported case of infantile Chlamydia trachomatispneumonitis diagnosed by BAL. In young infants presenting with diffuse pulmonary infiltrates and respiratory failure, the diagnosis of Chlamydia trachomatis should be entertained and ruled out by appropriate studies, including bronchoscopy and BAL. BAL fluid should be sent for rapid immunofluorescent antibody staining studies. Aggressive supportive and antimicrobial therapy may result in complete recovery from the initial insult. Parents of any infant with Chlamydia trachomatis infection should be evaluated and treated for occult infection to prevent progressive chlamydial genitourinary disease. Long-term follow-up should be provided these infants to assess their propensity to reactive airway disease and chronic obstructive lung disease.
Acknowledgment The writers thank Dr. Julius Schachter for performing the specific antichlamydia antibody titers on this patient's serum.
References
Fig. 1. Preintubation and postintubation radiographs showing bilateral interstitial and alveolar disease from Chlamydia traehomatis. Improvement in lung volumes is seen after bronehoalveolar lavage with PEEP of 10 em H,O.
1. Tipple MA, Beem MO, Saxon EM. Clinical characteristics of the afebrile pneumonia associated with Chlamydia trachomatis infection in infants less than six months of age. Pediatrics 1979; 63: 192-7. 2. Preece PM, Anderson JM, Thompson RO. Chlamydia trachomatis infection in infants: a prospective study. Arch Dis Child 1989; 64:525-9. 3. Beem MO, Saxon EM, Tipple MA. Treatment of Chlamydia pneumonia of infancy. Pediatrics 1979; 63:198-203. 4. McKenzie B, Wood RE, Bailey A. Airway management for unilateral lung lavage in children. Anesthesiology 1989; 70:550-3. 5. Leigh MW, Henshaw NO, Wood RE. Diagnosis of Pneumocystis carinii pneumonia in pediatric patients using bronchoscopic bronchoalveolar lavage. Pediatr Infect Dis 1985; 4:408-10. 6. Brasfield OM, Stagno S, Whitley RJ, et al. Infant pneumonitis associated with cytomegalovirus, Chlamydia, Pneumocystis, and Ureaplasma: followup. Pediatrics 1987; 79:76-83.
473
CASE REPORT
7. Klingebiel T, Pickert A, Dopfer R, et al. Unusual course of a Chlamydia pneumonia in an infant with IgG/IgG4 deficiency. Eur J Pediatr 1989; 148:431-4. 8. Radkowski MA, Kranzler JK, Beem MO, Tip-
pie MA. Chlamydia pneumonia in infants: radiography in 125 cases. AJR 1981; 137:703-6. 9. Lebel MH, Lamarre A, Rosseau E. Pneumothorax: new manifestation of Chlamydia trachomatis infection in infancy. Pediatr Pulmonol 1987; 3:
362-3. 10. Datta P, Laga M, Plummer FA, et al. Infection and disease after perinatal exposure to Chlamydia trachomatis in Nairobi, Kenya. J Infect Dis 1988; 158:524-8.
