13-10 Topic 7. Complicated Pneumonia
13-10 Topic 7. Complicated Pneumonia
13-10 Topic 7. Complicated Pneumonia
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Contents
CAP in HIV children Pnumonia and malignancy ARI in Down syndrome Pneumonia in CHD ARI in patient with neurological impairment
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Pneumonia is a leading cause of morbidity and death in HIV-infected children Cause of pneumonia
1. Bacterial pneumonia:
The incidence of pneumococcal bacteremia or invasive disease is 943-fold greater in HIV-infected children S. pneumoniae was the commonest pathogen followed by Staphylococcus aureus . The most common Gram-negative bacteria were Haemophilus influenzae , Escherichia coli or Salmonella species
2. Viral pneumonia
Viruses most commonly identified are CMV, RSV, influenza, human metapneumovirus, parainfluenza and adenovirus
Aetiology of pneumonia The data presented from the six countries indicate that the most common cause of pneumonia in HIV-infected children was bacterial, thus justifying the use of antibiotics in these children. The studies also show that viral pneumonia was relatively less common. The importance of PCP in HIV infection was recognized as a serious disease associated with higher mortality, particularly in children under the age of one year. Other important pathogens reported in HIV-infected children were CMV and TB.
WHO 2004; Consultative meeting on management of children with pneumonia and HIV infection, 30 31 Jan 2003, Harare, Zimbabwe.
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Pneumocystis jirovecii isolation and clinical signs There was variability in the methods of isolation of P. Jiroveci The efforts should be made to develop cheap and rapid methods of isolation for P. jiroveci. The clinical manifestation of PCP pneumonia included cyanosis and hypoxia with clear chest. There was little variation among the countries in the criteria used to consider clinical PCP. In most cases, the decision to treat PCP in the hospital was guided by the childs response to pneumonia treatment within 48 to 72 hours after which cotrimoxazole was added. The effectiveness of secondary prophylaxis was identified as an area for further investigation
WHO 2004; Consultative meeting on management of children with pneumonia and HIV infection, 30 31 Jan 2003, Harare, Zimbabwe.
Prophylaxis for PCP The use of effective prophylaxis early in life was a major concern as most countries in the region lacked the resources to determine the presence of HIV infection and risk of PCP. Treating all cases of very severe pneumonia for PCP or initiating empiric therapy based on clinical finding and later referring patients for intensive investigation was pointed out as an alternative. There was a need to develop guidelines for clinical predictors of PCP. Among HIV-infected children, the incidence of PCP falls rapidly from late infancy through the second year of life. PCP infection after one year of life was rare, therefore the relatively small added benefit of extending primary prophylaxis from 12 to 15 months of age needs to be supported by empirical data.
WHO 2004; Consultative meeting on management of children with pneumonia and HIV infection, 30 31 Jan 2003, Harare, Zimbabwe.
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Antibiotic regimen Most countries use the standard WHO regimens to treat severe pneumonia On the issue of use of penicillin or ampicillin with gentamicin versus cefotaxime/ceftriaxone, it was suggested that due to the high cost of the latter, the drug should be reserved as a secondline antibiotic for treatment failures with first-line antibiotics. It was also noted that more studies were documenting increasing pneumococcal resistance to cotrimoxazole. However, the issue of clinical efficacy and in vitro resistance is still on the agenda as previous studies showed that oral amoxicillin and cotrimoxazole have equal efficacy against non-severe pneumonia despite high in vitro resistance.
WHO 2004; Consultative meeting on management of children with pneumonia and HIV infection, 30 31 Jan 2003, Harare, Zimbabwe.
WHO recommendations on the management of diarrhoea and pneumonia in HIV-infected infant and children (revised; WHO 2010)
Aetiology of pneumonia Most HIV-infected children have recurrent pneumonia, irrespective of the etiology. The association of LIP and TB contributes to frequent episodes of pneumonia, leading to chronic lung disease and bronchiectasis. P. jirovecii was the most commonly identified etiological agent, with a summary odds ratio of 10.14 (95% confidence interval, 1.66;62.07) in ante-mortem studies and 9.08 (95% confidence interval, 2.49;33.09) in post-mortem studies
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Odds ratios for identifying specific pathogens in HIVinfected and -uninfected children with pneumonia
P. jirovecii pneumonia Data from Europe, Thailand and the USA showed that the peak prevalence of PCP in children was in infants under 12 months and usually under 6 months of age HIV infection increased the risk for death of severe or very severe pneumonia significantly, by sixfold overall. The effect of HIV infection on case fatality was largely confined to infants aged 212 months, and PCP contributed strongly to this effect PCP affected the HIV-related pneumonia case fatality rate, mainly among infants.
World Health Organization 2010
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Ages of HIV-infected infants and children with PCP in clinical studies in Africa
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Preventive interventions Co-trimoxazole prophylaxis has been the recommended standard of care for preventing PCP among HIV-infected and -exposed infants and children. Effectiveness of co-trimoxazole in reducing morbidity and mortality from pneumonia (presumed bacterial) among infants and children living with HIV in resource-limited settings. Other interventions Recommendations for other preventive interventions, such as vaccination against S. pneumoniae and H. influenzae type b and the promotion of breastfeeding.
World Health Organization 2010
Empirical co-trimoxazole treatment A systematic review of etiological pathogens strongly suggested an etiological role of PCP in young infants, particularly those with new HIV infection in the absence of treatment with cotrimoxazole and ART. The importance of covering clinically suspected PCP and endorsed previous recommendations for empirical treatment with cotrimoxazole. The panel also agreed that PCP is important only in children under 1 year of age
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Antibiotic regimens for non-severe pneumonia The current treatment recommendation for non-severe pneumonia is co-trimoxazole or amoxicillin (WHO, 2007) No randomized controlled trial designed on the basis of an a-priori hypothesis has been conducted to examine the efficacy of different regimens of antibiotics or case management for identified pneumonia, nor have any observational studies been reported on non-severe pneumonia in HIV-infected or -exposed children. The panel has therefore made no new recommendations
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Antibiotic regimens for severe and very severe pneumonia The importance of considering empirical antibiotic regimens with coverage against S. aureus and treating S. aureus infection in the absence of response to first-line antibiotic treatment. The panel did not recommend cephalosporin (first or second generation) for treatment of severe pneumonia The panel did recommend use of ceftriaxone as an alternative first-line antibiotic for treating very severe pneumonia or as a second-line option for children who do not respond to ampicillin plus gentamicin. In areas of high prevalence of methicillin-resistant S. aureus, use of cloxacillin or vancomycin is recommended when there is strong clinical suspicion or microbiological evidence of S. aureus pneumonia.
World Health Organization 2010
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Adjunctive corticosteroid treatment for suspected PCP The panel was uncertain whether adjunctive corticosteroid treatment for severe PCP affects latent CMV infection. Although a pooled analysis indicated a strong association between CMV infection and fatal HIV-associated pneumonia, the clinical significance remains unclear. The panel was concerned that progression of latent CMV infection could contribute to treatment failure of severe PCP among children receiving adjunctive corticosteroid.
Pneumocystis jirovecii had the strongest association with HIV infection, with a summary odds ratio of 10.1 (95% confidence interval CI, 17.7 62.1) and 9.1 (95% CI, 2.533.1) in antemortem and postmortem studies, respectively. Cytomegalovirus was strongly associated with HIV positivity among fatal cases of pneumonia (summary odds ratio 14.4; 95% CI, 6.7 30.8). There was a trend toward a greater prevalence of Staphylococcus aureus (odds ratio, 2.5; 95% CI, 0.95 6.4) in HIV-infected children.
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Characteristic of Descriptive Studies Analyzed to Characterize the Etiology of Community-acquired Pneumonia in HIV-infected Children
Author Mofenson et al14 Location USA Year(s) 19881991 19961997 1998 20002001 1999 2000 19961998 1995 Design Cohort Setting Clinical Cases (n) Diagnosis of Pneumonia 93* 26 151 185 105 35 48 Clinical and radiographic evidence Clinical and radiographic evidence WHO criteria of severe LRTI WHO criteria of severe LRTI WHO criteria of severe LRTI Not specied Clinical and radiographic evidence Included children died of pneumonia Included children died from lung disease
Chokephaibulkit et al17 Thailand Zar et Madhi et al15 Ruffini and Madhi3 Surve and Rathod20 Toro et al21 Nathoo et all9 Rennert et al18 al16 South Africa South Africa South Africa India Brazil Zimbabwe
Cross-sectional Clinical Cross sectional Cross sectional Cross sectional Cross sectional Cohort Clinical Clinical Clinical Clinical Clinical
Potential Causative Pathogens Identified Among HIV-infected Children With Community-acquired Pneumonia in the Descriptive Studies
Study Location Case (n) Percent Received PCP (%) CMV (%) PCP Prophylaxis Bacteria (%) MTB (%) RespiratoryVirus(%) Mixed Infection (%)
Clinical studies USA14 93* Thailand17 26 16 South Africa 151 15 South Africa 185 3 South Africa 105 India20 35 Brazil21 42 Postmortem studies Zimbabwe19 24 South Africa18 93
30 6 (6.5) 1 (1) 10 (10.7) 1 (1) 34 9 (34.6) N/A 15 (65) N/A 9.9 15 (10) N/A 18 (11.9) N/A 51.5 101/231(43.7) N/A 18/222 (8.1) 6/119 (5) 38 51 (48.6) 8/184)**8 (7.6) 3/60 (5) N/A 17 (48.6) N/A N/A 7 (20) 100 0 0 3 (7.1) 5 (12) N/A N/A 16 (67) 2 (8.3) 9 (37.5) 21 (22.6) 30 (32.3) 8 (8.6) 0 4 (4.3)
RSV: 4 (4.3) N/A N/A 26/226 (9.7) 11/94 (11.7) N/A N/A N/A N/A
N/A 2 (7.8) 2 (1.3) 6/222 (2.7) 5 (10) N/A N/A 5 (20.8) 15 (17.2)
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Study Characteristics of Comparative Studies Included in Determining the Etiology of Pneumonia in HIV-infected Children
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Prevalence of Specific Bacterial Pathogens Identified in HIV-infected and HIV-uninfected Children With Pneumonia
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Prevalence of Specific Bacterial Pathogens Identified in HIV-infected and HIV-uninfected Children With Pneumonia
Systematic Review on the Etiology and Antibiotic.. Tabel : Summary Likelihood Estimates of Identifying Specific Pathogens in HIVinfected Children Compared With HIV-uninfected Children With Pneumonia
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Authors conclusion A WHO panel used this review as well as analysis of risks and benefits to revise recommendations for antimicrobial treatment of CAP. Ampicillin plus gentamicin or ceftriaxone is now recommended as first-line empiric regimens for treating severe and very severe CAP in HIV-infected children. Treatment with cloxacillin or vancomycin is recommended in settings with a high incidence of MRSA and particularly if clinical or microbiological evidence of S. aureus pneumonia exist. Further studies in HIV-infected children on CAP etiology and antibiotic treatment are required in the era of antiretroviral treatment.
Pediatr Infect Dis J 2011;30: e192e202
Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the HIV. Among patients with HIV infection and PCP the mortality rate is 10 to 20% during the initial infection and increases substantially with the need for mechanical ventilation. It was suggested that in these patients corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality.
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Authors conclusions
The benefit of adjunctive corticosteroid therapy in HIV-infected patients with moderate-severe PCP. Estimated a relative risk reduction for overall mortality of 44% at 1 month and 32% at 3-4 months. Calculated that 9 patients must be treated with adjunctive corticosteroid in order to prevention one death in a setting where HAART is not available, and that 23 patients must be treated with adjunctive corticosteroid to prevent 1 death in a setting where HAART available. Support current recommendations for the management of PCP in HIVinfected patients All of studies in adult patients Children ??
The Cochrane Library 2009
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The HIV epidemic has changed the epidemiology of pneumonia. Evidence-based guidelines are needed to decrease CAP-related morbidity and mortality in children exposed to and infected with HIV. Currently, there is no standardized approach to antibiotic and/or adjunctive therapy for the management of CAP in countries with a high prevalence of paediatric HIV infection. Although adjunctive steroid therapy has been shown to be beneficial in the management of PCP in HIV-infected adults, its extrapolation to HIV-infected infants has limitations.
J Infect Dev Ctries 2012; 6(2):109-119
Summary of findings table for the use of adjunctive corticosteroid for Pneumocystis jirovecii pneumonia in HIV-infected children
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Quality of evidence, comparative risk of adjunctive corticosteroid treatment for Pneumocystis jirovecii pneumonia in HIV-infected children by type of outcomes based on GRADE guideline
No a priori planned RCT were identified, only subgroup analyses of an RCT comparing oral amoxicillin versus parenteral penicillin for severe pneumonia in children. HIV-infected children had significantly higher treatment failure rates compared to their uninfected counterparts. An RCT study investigating adjunctive corticosteroid therapy : failed to identify a statistically significant reduction in mortality with a relative risk of 0.57 (95% CI 0.301.07). A before-after observational study showed substantial beneficial effect of corticosteroid treatment in reducing mortality. Authors conclusion : Insufficient evidence exists to identify effective antimicrobial treatment regimens for HIV-associated pneumonia in paediatric populations or confirm the beneficial effect of corticosteroid treatment for HIV-infected children with PCP J Infect Dev Ctries 2012; 6(2):109-119
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Lymphocytic interstitial pneumonitis (LIP) is estimated to occur in 3040% of HIV-infected children LIP generally has an insidious clinical presentation in HIV infected children older than 2 years of age. Typical manifestations are a non-productive cough and mild hypoxaemia together with generalized lymphadenopathy and finger clubbing. LIP may also be associated with painless bilateral parotid gland enlargement.
Clinical Radiology 65 (2010) 150154
However, appreciation of the characteristic clinical and radiological features of LIP in HIV-infected children resulted in the CDC formulating criteria for a presumptive diagnosis of LIP in 1987, obviating the need for lung biopsy. Radiological criteria are persistence of diffuse, symmetrical, reticulo-nodular, or nodular pulmonary opacification , with or without mediastinal adenopathy, for at least 2 months, with neither an identifiable pathogen nor a response to antibiotic therapy.
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Authors conclusion: The 1987 CDC criteria for a presumptive diagnosis of LIP remain valid, as 7592% of all biopsy-proven cases of LIP in HIV-infected children would have been diagnosed using these.
Clinical Radiology 65 (2010) 150154
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The H1N1 influenza virus can cause serious disease in immunosuppressed patients. Clinical findings include respiratory failure, treatment failures due to drug resistance, and death Several concepts appear to emerge:
rapid diagnosis using PCR is critical for identifying infected patients initiating antiviral treatment implementing appropriate infection controls.
Recommended a higher dose of oseltamivir in analogy to recommendations for H5N1 avian influenza.
Blood. 2010;115:1331-1342)
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RSV is a significant cause of morbidity in previously healthy infants, but disease generally is more severe and often is fatal in immunosuppressed patient Authors conclusions: Profound lymphopenia and young age as independent predictors of RSV-related lower respiratory tract infections in immunocompromised children. No association between neutropenia and RSV-related morbidity or death was found. These findings can guide interventions for respiratory syncytial virus infection in high risk hosts.
PEDIATRICS 2008; 121(2)
Non-AIDS
Days +++ +++ + Low Moderate Not well defined Higher
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Twelve randomized trials were identified, including 1245 patients (50% children) who had undergone autologous bone marrow or solid organ transplant or who had hematologic cancer. When TMP-SMX was administered, a 91% reduction was observed in the occurrence of PCP (RR, 0.09; 95% CI, 0.02-0.32); the number needed to treat was 15 (95% CI,13-20) patients, with no heterogeneity. Pneumocystis pneumoniarelated mortality was significantly reduced (RR, 0.17; 95% CI, 0.03-0.94), whereas all-cause mortality did not differ significantly (RR, 0.79; 95% CI, 0.18-3.46). Adverse events that required discontinuation occurred in 3.1% of adults and none of the children, and all were reversible. No differences between once-daily and thrice-weekly administration schedules were found.
Mayo Clin Proc. 2007;82(9):1052-1059
Occurrence of PCP infections after treatment with TMPSMX vs placebo, no treatment, or treatment with a non-PCP antibiotic.
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PCPrelated mortality after treatment TMP-SMX vs placebo, no treatment, or treatment with a non-PCP antibiotic.
Occurrence of Pneumocystis pneumonia infections after oncedaily vs thrice-weekly oral administration of TMP-SMX.
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Authors conclusion Prophylaxis with TMP-SMX significantly reduced PCP infections and PCP-related mortality in immunocompromised nonHIV-infected patients at risk for PCP. Balanced against severe adverse events, PCP prophylaxis is warranted when the risk for PCP is higher than 3.5% for adults. Adverse events are less frequent in children, for whom prophylaxis might be warranted at lower PCP incidence rates.
Mayo Clin Proc. 2007;82(9):1052-1059
Adjunctive treatment with high-dose steroids (HDS) was associated with a dramatic decrease in mortality during PCP episodes in HIV-positive patients HIV-negative patients ? The pathophysiology of PCP may differ between HIV-positive and HIV-negative patients. Authors Conclusions: High Dose Steroid were associated with increased mortality in HIVnegative patients with PCP via a mechanism independent from an increased risk of infection Sample is adult patients Children ??
Respiratory Research 2013, 14:87
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Patient characteristics at admission and univariate analysis of risk factors associated with mortality
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Selected immunological and non-immunological factors that potentially increase the susceptibility to infections in Down syndrome
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The possibilities risk factors for severe RSV LRTI in children with DS.
Pulmonary vascular resistance hypertension An abnormal upper airway physiology A decreased lung function An altered immune response
Authors conclusion: Down syndrome is a novel independent risk factor for severe respiratory syncytial virus lower respiratory tract infections. The effect of respiratory syncytial virus prophylaxis in this specific population needs to be established.
Pediatrics 2007;120;e1076
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the blood is shunted through an abnormal opening from the left to the right side of the heart increase in pulmonary blood flow and increased cardiac workload (including ventricular strain, dilation, and hypertrophy) A left-to-right shunt can adversely affect lung function, and superimposed lower respiratory tract infections cause additional compromise lead to respiratory failure
Mediterr J Hematol Infect Dis 2013, 5(1): e2013028
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RECOMMENDATIONS Every child, no matter what the degree of disability, deserves individualised assessment of her/his respiratory problems.. Assessment is based on the pattern of symptoms and contributing factors given the underlying disability. Multidisciplinary assessments are often required to tease out the multifactorial aetiology. Intervention is aimed at optimising quality of life for the child foremost. The views and welfare of the parents must be taken into account.
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THANK YOU
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