eMedicine Specialties > Pediatrics: General Medicine > Pulmonology
Afebrile Pneumonia Syndrome: Treatment & Medication
Updated: Jan 7, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Usually, the degree of afebrile pneumonia syndrome (APS) is mild, although clinical and radiographic findings may appear out of proportion (particularly in infants with C trachomatis infection); most infants do not require diagnostic evaluation or hospitalization. Infants who present with more severe illness may need empiric treatment to be instituted promptly, foregoing the risk of delay and expense of an extensive diagnostic evaluation. These infants often have viral illness, which does not respond to antibiotic therapy, but differentiating bacterial from viral illness is often difficult. Consider empiric antibiotic therapy if the potential benefits of early intervention outweigh the risks of unnecessary treatment.
Consultations
Consultation with specialists in pulmonary and infectious diseases may be helpful for more serious disease or in difficult cases.
Diet
No particular diet is required.
Medication
Infants in whom the clinical picture suggests afebrile pneumonia syndrome (APS) may benefit from a 10-day to 14-day course of erythromycin. Newer macrolides and azalides are also effective and may be tolerated better (particularly azithromycin). Recent reports suggest an association of early receipt of erythromycin and development of hypertrophic pyloric stenosis. Whether such an association will be substantiated or whether the effect will extend to clarithromycin or azithromycin is unclear. Thus, antimicrobial therapy for APS should be considered in light of this potential adverse outcome. Antiviral therapy is used in the treatment of CMV, but only when unusually severe disease or immunocompromise is present. Although ribavirin is available for the treatment of RSV, disease sufficiently severe enough to merit treatment would not be APS and is beyond the scope of this discussion.
Antibiotics
These are used for presumptive treatment of C trachomatis and U urealyticum infection. Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Guide antibiotic selection by blood culture sensitivity whenever feasible.
Erythromycin (E.E.S., E-Mycin, Eryc)
DOC because of cost, safety, and experience. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. For management of staphylococcal and streptococcal infections.
Adult
1-4 g/d PO divided q6-8h; not to exceed 4 g/d
Pediatric
40 mg/kg/d PO divided qid for 14 d
Inhibits CYP450 1A2, 3A3/4 isoenzymes; coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis; decreases metabolism of repaglinide, thus increasing serum levels and effects
Documented hypersensitivity; hepatic impairment; do not use in combination with cisapride
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in liver disease; estolate formulation may cause cholestatic jaundice; adverse GI tract effects are common (give doses pc); discontinue if nausea, vomiting, malaise, abdominal colic, or fever occurs
Azithromycin (Zithromax)
May become DOC because of safety profile, ease of use, and improved GI tract tolerability relative to erythromycin. Administer caps and PO susp on an empty stomach, at least 1 h before or 2 h after meals. Tabs and PO powder (sachet) may be administered with food.
Adult
Day 1: 500 mg PO
Days 2-5: 250 mg/d PO
Pediatric
<6 months: Not established
>6 months:
Day 1: 10 mg/kg PO once; not to exceed 500 mg/d
Days 2-5: 5 mg/kg/d PO; not to exceed 250 mg/d
May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients
Clarithromycin (Biaxin)
Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
May be a substitute for erythromycin if compliance is a likely problem.
Adult
250-500 mg PO bid for 14 d
Pediatric
15 mg/kg/d PO divided bid for 14 d
Inhibits CYP450 3A4; may cause cardiac arrhythmias in patients also receiving terfenadine, astemizole, and cisapride; toxicity increases with coadministration of fluconazole and pimozide; effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, theophylline, tacrolimus, digoxin, carbamazepine, ergot alkaloids, triazolam, HMG-CoA reductase inhibitors
Plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increases in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents; decreases metabolism of repaglinide, thus increasing serum levels and effects
Documented hypersensitivity; coadministration of pimozide
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; give half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies; adverse effects include diarrhea, nausea, abnormal taste, dyspepsia, headache, and abdominal discomfort; may be administered with food
Antivirals
These are used to treat CMV. Ganciclovir is the DOC for documented CMV pneumonitis. Use foscarnet if ganciclovir-resistant virus is identified or if adverse effects prevent ongoing use. Oral valganciclovir is under investigation for use in the treatment of congenital or neonatal CMV.
Ganciclovir (Cytovene)
DOC. Synthetic guanine derivative active against CMV. An acyclic nucleoside analog of 2'-deoxyguanosine that inhibits replication of herpes viruses both in vitro and in vivo.
Levels of ganciclovir-triphosphate are as much as 100-fold higher in CMV-infected cells than in uninfected cells, possibly due to preferential phosphorylation of ganciclovir in virus-infected cells.
Adult
10 mg/kg/d IV divided q12h for 14-21 d; 5 mg/kg/d may be required for maintenance
Pediatric
Administer as in adults
Concomitant administration with cytotoxic drugs, such as dapsone, vinblastine, doxorubicin, pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim/sulfamethoxazole combinations, or other nucleoside analogs, may result in additive toxicity in bone marrow, spermatogonia, and germinal layers of skin and GI tract mucosa (coadminister only if potential benefits outweigh risks); coadministration with imipenem-cilastatin may cause generalized seizures (use only if potential benefits outweigh risks); serum creatinine levels may increase following concurrent use of ganciclovir with either cyclosporine or amphotericin B
In presence of probenecid, ganciclovir renal clearance is reduced; bioavailability may increase when didanosine is administered either 2 h prior to or simultaneously with ganciclovir; bioavailability of ganciclovir may decrease in presence of zidovudine, while bioavailability of zidovudine is increased in presence of ganciclovir
Documented hypersensitivity; do not administer IM/SC
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Limited experience with use in children <12 y; clinical toxicity includes granulocytopenia, anemia, and thrombocytopenia; half-life and plasma/serum concentrations may be increased because of reduced renal clearance; doses > 6 mg/kg IV may result in increased toxicity; rapid infusions may result in increased toxicity; initially, reconstituted solutions of IV ganciclovir have a high pH (11); phlebitis or pain may occur at site of IV infusion despite further dilution in IV fluids
Accompany administration of ganciclovir with adequate hydration; photosensitization (photoallergy or phototoxicity) may occur; adverse effects include neutropenia, thrombocytopenia, retinal detachment, and confusion; drug reactions are alleviated with dose reduction or temporary interruption
Foscarnet (Foscavir)
Organic analog of inorganic pyrophosphate that inhibits replication of known herpesviruses, including CMV, HSV-1, and HSV-2. Inhibits viral replication at pyrophosphate-binding site on virus-specific DNA polymerases. Poor clinical response or persistent viral excretion during therapy may be due to viral resistance.
Patients who can tolerate foscarnet well may benefit from initiation of maintenance treatment at 120 mg/kg/d early in treatment. Individualize dosing based on renal function status.
Adult
180 mg/kg/d IV divided q8h for 24 h, then 90 mg/kg/d IV divided q8h for 14-21 d
Pediatric
Administer as in adults
Coadministration with potentially nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine) may increase nephrotoxicity (do not administer unless potential benefits outweigh risks); coadministration with IV pentamidine may cause hypocalcemia
Documented hypersensitivity; serum creatinine level >2.9 mg/dL
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause decline in renal function; for correct dosing, obtain 24-h serum creatinine levels at baseline and continue to monitor (discontinue if serum creatinine level is >2.9 mg/dL); hydration may reduce nephrotoxicity; hypercalcemia (increased risk if administered with pentamidine), hypokalemia, and hypomagnesemia may occur (carefully monitor electrolyte levels); assess for electrolyte and mineral level abnormalities if mild perioral numbness, paresthesias symptoms, or seizures occur; granulocytopenia and anemia may occur (regularly monitor CBC counts)
Infuse into veins with adequate blood flow to avoid local irritation; to avoid toxicity, do not administer by rapid or bolus IV injection; may cause peripheral neuropathy, seizures, hallucinations, GI tract disturbances, increased levels of serum hepatic transaminases, hypertension, chest pain, abnormal electrocardiogram results, coughing, dyspnea, bronchospasm, and renal failure
More on Afebrile Pneumonia Syndrome |
| Overview: Afebrile Pneumonia Syndrome |
| Differential Diagnoses & Workup: Afebrile Pneumonia Syndrome |
 Treatment & Medication: Afebrile Pneumonia Syndrome |
| Follow-up: Afebrile Pneumonia Syndrome |
| References |
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References
Brewster DR, De Silva LM, Henry RL. Chlamydia trachomatis and respiratory disease in infants. Med J Aust. Oct 3 1981;2(7):328-30. [Medline].
Brasfield DM, Stagno S, Whitley RJ, et al. Infant pneumonitis associated with cytomegalovirus, Chlamydia, Pneumocystis, and Ureaplasma: follow-up. Pediatrics. Jan 1987;79(1):76-83. [Medline].
Chen CJ, Wu KG, Tang RB, Yuan HC, Soong WJ, Hwang BT. Characteristics of Chlamydia trachomatis infection in hospitalized infants with lower respiratory tract infection. J Microbiol Immunol Infect. Jun 2007;40(3):255-9. [Medline].
Beem MO, Saxon E, Tipple MA. Treatment of chlamydial pneumonia of infancy. Pediatrics. Feb 1979;63(2):198-203. [Medline].
Radkowski MA, Kranzler JK, Beem MO, et al. Chlamydia pneumonia in infants: radiography in 125 cases. AJR Am J Roentgenol. Oct 1981;137(4):703-6. [Medline].
Geis T, Schilling S, Segerer H. [A Young Infant with Afebrile Pneumonia Caused by Chlamydia Trachomatis]. Klin Padiatr. Aug 3 2006;[Medline].
Abzug MJ, Beam AC, Gyorkos EA, Levin MJ. Viral pneumonia in the first month of life. Pediatr Infect Dis J. Dec 1990;9(12):881-5. [Medline].
Arnold JC, Singh KK, Spector SA, Sawyer MH. Undiagnosed respiratory viruses in children. Pediatrics. Mar 2008;121(3):e631-7. [Medline].
Beem MO, Saxon EM. Respiratory-tract colonization and a distinctive pneumonia syndrome in infants infected with Chlamydia trachomatis. N Engl J Med. Feb 10 1977;296(6):306-10. [Medline].
Brieu N, Guyon G, Rodière M, Segondy M, Foulongne V. Human bocavirus infection in children with respiratory tract disease. Pediatr Infect Dis J. Nov 2008;27(11):969-73. [Medline].
Camps M, Ricart S, Dimova V, et al. Prevalence of human metapneumovirus among hospitalized children younger than 1 year in Catalonia, Spain. J Med Virol. Aug 2008;80(8):1452-60. [Medline].
Chiang YC, Shyur SD, Huang LH, et al. Chlamydia trachomatis pneumonia: experience in a medical center. Acta Paediatr Taiwan. Sep-Oct 2005;46(5):284-8. [Medline].
Cilla G, Onate E, Perez-Yarza EG, Montes M, Vicente D, Perez-Trallero E. Viruses in community-acquired pneumonia in children aged less than 3 years old: High rate of viral coinfection. J Med Virol. Oct 2008;80(10):1843-9. [Medline].
Colaizy TT, Morris CD, Lapidus J, Sklar RS, Pillers DA. Detection of ureaplasma DNA in endotracheal samples is associated with bronchopulmonary dysplasia after adjustment for multiple risk factors. Pediatr Res. May 2007;61(5 Pt 1):578-83. [Medline].
Darville T. Chlamydia trachomatis infections in neonates and young children. Semin Pediatr Infect Dis. Oct 2005;16(4):235-44. [Medline].
Davies HD, Wang EEL. Special pulmonary syndromes. In: Principles and Practice of Pediatric Infectious Diseases. Churchill Livingstone; 1997:269-77.
DeMuri GP. Afebrile pneumonia in infants. Prim Care. Dec 1996;23(4):849-60. [Medline].
Dworsky ME, Stagno S. Newer agents causing pneumonitis in early infancy. Pediatr Infect Dis. May-Jun 1982;1(3):188-95. [Medline].
Fasoli L, Paldanius M, Don M, et al. Simkania negevensis in community-acquired pneumonia in Italian children. Scand J Infect Dis. 2008;40(3):269-72. [Medline].
Fleisher GR, Rosenberg N, Vinci R, et al. Intramuscular versus oral antibiotic therapy for the prevention of meningitis and other bacterial sequelae in young, febrile children at risk for occult bacteremia. J Pediatr. Apr 1994;124(4):504-12. [Medline].
Geis T, Schilling S, Segerer H. [A young infant with afebrile pneumonia caused by Chlamydia trachomatis]. Klin Padiatr. Mar-Apr 2008;220(2):91-2. [Medline].
Gilbert GL. Treatment of chlamydial and mycoplasmal genital infections. Med J Aust. Feb 16 1987;146(4):205-8. [Medline].
Hammerschlag MR. Chlamydia trachomatis and Chlamydia pneumoniae infections in children and adolescents. Pediatr Rev. Feb 2004;25(2):43-51. [Medline].
Han BK, Son JA, Yoon HK, Lee SI. Epidemic adenoviral lower respiratory tract infection in pediatric patients: radiographic and clinical characteristics. AJR Am J Roentgenol. Apr 1998;170(4):1077-80. [Medline].
Heiskanen-Kosma T, Paldanius M, Korppi M. Simkania negevensis may be a true cause of community acquired pneumonia in children. Scand J Infect Dis. 2008;40(2):127-30. [Medline].
Larsen HH, von Linstow ML, Lundgren B, Hogh B, Westh H, Lundgren JD. Primary pneumocystis infection in infants hospitalized with acute respiratory tract infection. Emerg Infect Dis. Jan 2007;13(1):66-72. [Medline].
McCarthy VP, Zimmerman AW, Miller CA. Central nervous system manifestations of parainfluenza virus type 3 infections in childhood. Pediatr Neurol. May-Jun 1990;6(3):197-201. [Medline].
Meissner HC, Murray SA, Kiernan MA, et al. A simultaneous outbreak of respiratory syncytial virus and parainfluenza virus type 3 in a newborn nursery. J Pediatr. May 1984;104(5):680-4. [Medline].
Nagayama Y, Sakurai N, Yamamoto K, et al. Isolation of Mycoplasma pneumoniae from children with lower-respiratory-tract infections. J Infect Dis. May 1988;157(5):911-7. [Medline].
Ollikainen J. Perinatal Ureaplasma urealyticum infection increases the need for hospital treatment during the first year of life in preterm infants. Pediatr Pulmonol. Nov 2000;30(5):402-5. [Medline].
Robertson J, Shilkofski N. Drug doses. In: Harriet Lane Handbook: A Manual for Pediatric House Officers. Philadelphia, Pa: Mosby; 2005:679-1009.
Rubin EE, Quennec P, McDonald JC. Infections due to parainfluenza virus type 4 in children. Clin Infect Dis. Dec 1993;17(6):998-1002. [Medline].
Rudd PT, Waites KB, Duffy LB, et al. Ureaplasma urealyticum and its possible role in pneumonia during the neonatal period and infancy. Pediatr Infect Dis. Nov-Dec 1986;5(6 Suppl):S288-91. [Medline].
Schaad UB, Rossi E. Infantile chlamydial pneumonia--a review based on 115 cases. Eur J Pediatr. Mar 1982;138(2):105-9. [Medline].
Schweich P, Schidlow DV, Srinivasan R. Afebrile pneumonitis in infants: predictors of outcome. Pediatr Emerg Care. Mar 1987;3(1):1-4. [Medline].
Stagno S, Brasfield DM, Brown MB, et al. Infant pneumonitis associated with cytomegalovirus, Chlamydia, Pneumocystis, and Ureaplasma: a prospective study. Pediatrics. Sep 1981;68(3):322-9. [Medline].
Stagno S, Pifer LL, Hughes WT, et al. Pneumocystis carinii pneumonitis in young immunocompetent infants. Pediatrics. Jul 1980;66(1):56-62. [Medline].
Syrogiannopoulos GA, Kapatais-Zoumbos K, Decavalas GO, et al. Ureaplasma urealyticum colonization of full term infants: perinatal acquisition and persistence during early infancy. Pediatr Infect Dis J. Apr 1990;9(4):236-40. [Medline].
Tan BH, Lim EA, Seah SG, et al. The incidence of human bocavirus infection among children admitted to hospital in Singapore. J Med Virol. Jan 2009;81(1):82-9. [Medline].
Tipple MA, Beem MO, Saxon EM. Clinical characteristics of the afebrile pneumonia associated with Chlamydia trachomatis infection in infants less than 6 months of age. Pediatrics. Feb 1979;63(2):192-7. [Medline].
Vargas SL, Hughes WT, Santolaya ME, et al. Search for primary infection by Pneumocystis carinii in a cohort of normal, healthy infants. Clin Infect Dis. Mar 15 2001;32(6):855-61. [Medline].
Vincent JM, Cherry JD, Nauschuetz WF, et al. Prolonged afebrile nonproductive cough illnesses in American soldiers in Korea: a serological search for causation. Clin Infect Dis. Mar 2000;30(3):534-9. [Medline].
Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. Aug 4 2006;55(RR-11):1-94. [Medline].
Zaitsu M. The development of asthma in wheezing infants with Chlamydia pneumoniae infection. J Asthma. Sep 2007;44(7):565-8. [Medline].
Zar HJ. Neonatal chlamydial infections: prevention and treatment. Paediatr Drugs. 2005;7(2):103-10. [Medline].
Zhang LL, Tang LY, Xie ZD, et al. Human bocavirus in children suffering from acute lower respiratory tract infection in Beijing Children's Hospital. Chin Med J (Engl). Sep 5 2008;121(17):1607-10. [Medline].
Further Reading
Keywords
afebrile pneumonia syndrome, APS, adenovirus, atypical pneumonia, bronchiolitis, Chlamydia trachomatis, chlamydial pneumonitis, conjunctivitis, croup, cytomegalovirus, CMV, human bocavirus, human metapneumovirus, infantile pneumonitis, interstitial pneumonia, laryngotracheobronchitis, newborn infection, nonbacterial pneumonia, obstructive airway disease, parainfluenza virus, pharyngitis, Pneumocystis jiroveci, pneumonia, pneumonitis, respiratory syncytial virus, RSV, rhinorrhea, RTI, tachypnea, upper respiratory tract infection, URI, Ureaplasma urealyticum, viral pneumonia
