Opportunistic infections in pediatrics: when to suspect and how to approach

Moraes-Pinto, Maria Isabel de; Ferrarini, Maria Aparecida Gadiani

doi:10.1016/j.jped.2019.09.008

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Sumário

Review articles • J. Pediatr. (Rio J.) 96 (suppl 1) • Mar-Apr 2020 • https://doi.org/10.1016/j.jped.2019.09.008 copy

Opportunistic infections in pediatrics: when to suspect and how to approach^☆ ☆ Please cite this article as: de Moraes-Pinto MI, Ferrarini MA. Opportunistic infections in pediatrics: when to suspect and how to approach. J Pediatr (Rio J). 2020;96(S1):47-57.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objectives

To describe the characteristics of opportunistic infections in pediatrics regarding their clinical aspects, as well as the diagnostic strategy and treatment.

Source of data

Non-systematic review of literature studies in the PubMed database.

Synthesis of data

Opportunistic infections caused by non-tuberculous mycobacteria, fungi, Herpesvirae, and infections affecting individuals using immunobiological agents are analyzed. Because these are severe diseases with a rapid evolution, diagnostic suspicion should be early, associated with the patient's clinical assessment and history pointing to opportunistic infections. Whenever possible, samples of secretions, blood, and other fluids and tissues should be collected, with early therapy implementation.

Conclusions

Despite the improved diagnosis of opportunistic infections in recent years, they remain a challenge for pediatricians who are not used to these infections. They should raise the suspicion and start treating the case, but should also resort to specialists in the management of these infections to provide a better outcome for these patients, who still have high mortality.

Keywords
Mycobacterium infections; Fungemia; Candidiasis; Immunobiological herpesviridae; Alpha tumor necrosis factor

Mycobacterium tuberculosis complex	M. tuberculosis, M. bovis, M. africanum, M. microti, M. canetti, M. caprae, M. pinnipedii, M. suricattae, M. mungi
Leprosy-causing mycobacteria	M. leprae, M. lepromatosis
Slow-growing non-tuberculous mycobacteria	M. avium complex -M. intracellulare and M. avium
	M. kansasii, M.xenopi, M. malmoense, M. szulgai, M. ulcerans
Fast growing non-tuberculous mycobacteria	M. abscessus, M. chelonae, M. fortuitum, M. marinum, among others

Pathology	Agent	Diagnosis	Treatment^a a Use at least three drugs and associate others according to clinical evolution.	Duration
Pulmonary, nodular infection, or bronchiectasis	M. avium complex	Respiratory secretion culture	Clarithromycin or azithromycin + ethambutol + rifampicin or rifabutin	18-24 months, maintaining for another 12 months after negative culture
			In the fibrocavitary or disseminated form: associate streptomycin or amikacin
Pulmonary infection	M.kansasii	Respiratory secretion culture	Rifampicin + ethambutol + clarithromycin + levofloxacin or moxifloxacin	Minimum of 12 months after negative culture
			Consider streptomycin in severe disease
Pulmonary infection	M.abscessus	Respiratory secretion culture	Imipenem or cefoxitin	Choose drugs according to antibiogram
			Amikacin, clarithromycin	Pulmonary infection: maintain for 12 months after negative culture
			Tigecycline or doxycycline (in those older than 8 years)

Pathology	Agent	Diagnosis	Treatment	Duration
Disseminated candidiasis	Candida albicans	Antigen test (β1,3 glucan) Blood culture	1^st choice: echinocandins: micafungin	Maintain for at least 14 days after negative culture
			2^nd choice: amphotericin B
			3^rd choice: fluconazole
	Candida glabrata	Antigen test (β1,3 glucan) Blood culture	1^st choice: echinocandins
			2^nd choice: amphotericin B
	Candida auris	Antigen test (β1,3 glucan) Blood culture	Multiresistant
			Echinocandin associated with amphotericin B
Invasive aspergillosis	Aspergillus fumigatus	Serial pulmonary computed tomography: pulmonary nodules and halo sign, air crescent sign	Immunosuppression removal and control of underlying disease	Between 6 and 12 weeks and as long as radiological lesions persist
		Direct screening and culture for Aspergillus spp	1^st choice: voriconazole
		Plasma galactomannan, bronchoalveolar lavage, or cerebrospinal fluid	Others: itraconazole, posaconazole, isavuconazole
		Persistently negative values: high negative predictive value for disease (β1,3 glucan) in serum	Liposomal amphotericin
		PCR in biological fluids - under investigation	Echinocandin
			Caspofungin combined with voriconazole in refractory invasive disease.
Disseminated fusariosis	Fusarium solani and others	Screening and culture for skin or blood culture fungus	Amphotericin B deoxycholate	Adapt according toclinical evolution
		β1, 3 glucan.	Liposomal amphotericin B
		Radiology: interstitial pulmonary infiltrate and nodules or caves	Voriconazole
Pneumocystosis	P. jiroveci	Direct screening for P. jiroveci	Sulfamethoxazole + trimethoprim	21 days
		PCR in bronchoalveolar lavage or sputum
Disseminated or central nervous system cryptococcosis	C. gatti and C. neoformans	CSF and serum antigen screening	Amphotericin B deoxycholate + 5 flucytosine	Induction: 15 days
		Culture of body fluids and biopsy material	Fluconazole	Maintenance: 8 weeks minimum
Mucormycosis	Rhizopus (R. arrhizus), Mucor (M. circinelloides), Rhizomucor (R. pusillus), Cunninghamella (C. bertholletiae), Absidia (A. corymbifera)	Tomography: halo sign, inverted halo sign, pleural effusions, pulmonary nodules	Amphotericin B deoxycholate or liposomal amphotericin	Prolonged time
		Direct examination of nasal mucosa scraping, facial sinus aspiration, sputum, or bronchoalveolar lavage:	Posaconazole	Surgical removal of focus
		broad, non-septate hyaline hyphae with 90º-angle branches.		Limited data on children
		Anatomopathological test; culture (sensitivity: 50%)

Pathology	Agent	Diagnosis	Treatment	Duration
Mucocutaneous herpes simplex and encephalitis	HHV-1 and HHV-2	Immunofluorescence-confirmed cell culture; PCR in CSF or vesicle material	Intravenous acyclovir	14-21 days
Varicella or disseminated herpes zoster	HHV-3 (varicella)	PCR in CSF, vesicle, or scab material	Intravenous acyclovir	7-10 days
Varicella without dissemination	HHV-3 (varicella)	PCR in vesicle or scab material	Valacyclovir orally	5 days
EBV infection with significant tonsillar hypertrophy, splenomegaly, myocarditis, hemolytic anemia, and hemophagocytic syndrome	HHV-4 (EBV)	Serum, plasma, and tissue PCR and real-time PCR in lymphoid cells, tissues, and body fluids	Antiviral therapy with no established benefit	10days
			Corticosteroids
Cytomegalovirus infection	HHV-5 (CMV)	Traditional or shell-vial culture of affected organ material or PCR of blood and other body fluids	Intravenous ganciclovir followed by secondary prophylaxis with valganciclovir	Treatment:14-21 days
				Secondary prophylaxis up to CD4 > 100/mm³ or >15% for 6 consecutive months
Disseminated infection with or without encephalitis	HHV-6B	Only available in research laboratories	Ganciclovir or foscarnet	Not defined
Kaposi's sarcoma	HHV-8	PCR in blood, body fluids, or biopsy material	Usually treated with radiotherapy and chemotherapy	-

Target	Agent	Associated infections in pediatrics
TNF-alpha	Infliximab	Upper airway infection, pneumonia, abscesses, varicella, histoplasmosis, meningitis by Listeria monocytogenes, cutaneous blastomycosis, M. avium infection
	Adalimumab
	Etanercept
IL-1	Anakinra	Visceral leishmaniasis, varicella, type 1 and 2 herpes simplex, upper airway infection
	Canakinumab
IL-2	Basiliximab	-
IL-6	Tocilizumab	Upper airway infection, pneumonia, cellulitis, varicella
IL-12/23	Ustekinumab	-
CD28 blocker	Abatacept	-
Alpha-4 integrin	Vedolizumab	Upper airway infection, cellulitis
JAK	Tofacitinib	Viral infections (BK, cytomegalovirus, adenovirus), bacterial infections
CD20	Rituximab	Viral infections (varicella, cytomegalovirus, adenovirus), pneumonia, empyema, mastoiditis, Salmonella enteritidis, and candidiasis

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E-mail: jped@jped.com.br

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[1] * Corresponding author. E-mail:m.isabelmp@gmail.com (M.I. de Moraes-Pinto).

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Opportunistic infections in pediatrics: when to suspect and how to approach☆ ☆ Please cite this article as: de Moraes-Pinto MI, Ferrarini MA. Opportunistic infections in pediatrics: when to suspect and how to approach. J Pediatr (Rio J). 2020;96(S1):47-57.

Abstract

Objectives

Source of data

Synthesis of data

Conclusions

Opportunistic infections in pediatrics: when to suspect and how to approach^☆ ☆ Please cite this article as: de Moraes-Pinto MI, Ferrarini MA. Opportunistic infections in pediatrics: when to suspect and how to approach. J Pediatr (Rio J). 2020;96(S1):47-57.