DISCUSSION:
In the current study, patients diagnosed with CCAP at presentation were
older than those diagnosed with CCAP. Sex and comorbidities were not
significant risk factors for CCAP. Meanwhile, age below 2 years, male
sex, and comorbidities were associated with invasive pneumococcal
infections16,27,28. However, age, sex, and
comorbidities were not significant risk factors for pneumococcal
pneumonia. In a study conducted in Israel, there was no significant
difference in age between CAP and CCAP patients. Moreover, age
<2 years was not a risk factor for CCAP
development29. Immunodeficiencies and suppurative lung
diseases may cause CAP. However, CCAPs are generally observed in
children who do not have comorbidities and who were previously
healthy29. In a 540 patient series in the USA in 2002,
children diagnosed with EMP were older (mean age = 6 years, p
< 0.001) than those who were followed-up for
CAP30. In a study that assessed the 10-year medical
records of patients in Canada and France, CCAP was found to account for
51%–57% of all hospital admissions among children aged below 5
years28,31 Similar findings were also observed in a
study including 767 patients (mean age = 4.1 years, p = 0.02) in France
in 2010,31.
In this study, the presence of cough, chest pain, and fever and
pre-admission time of these symptoms and a history of pneumonia were not
considered risk factors for CCAP. Respiratory distress (tachypnea and
retraction) and hypoxia were significantly associated with CCAP. Severe
CAP is defined as the presence of fever; capillary filling time
>2 s; dehydration; inability to feed; subcostal, nasal, and
substernal retraction; tachypnea (infants, >70 cycles/min
and older children, >50 cycles/min); cyanosis; and moaning,
according to the British Thoracic Society 2011 guideline4. Based on these parameters, CCAP is more common in
hospitalized patients diagnosed with severe
pneumonia4,5.
In our study, CCAP patients were commonly underweight. Even in the
absence of severe malnutrition, underweight is associated with an
increased pneumonia risk32. Wexler ID et al. conducted
a study in Israel. Results showed that CCAP patients were often
underweight, and this finding is similar to ours. However, the condition
is not an independent risk factor for CCAP
development9.
In our study, CCAP patients had a high CRP level at time of enrollment.
Moreover, both groups had a high ESR and leukocyte and thrombocyte
counts during admission. In the study of Huang C-Y et al., elevated CRP
level and leukocyte count upon admission were a significant factor for
CCAP development10. In a multicenter study that
retrospectively analyzed 111 pneumonia patients in 2006, significant
differences in terms of ESR and leukocyte and platelet counts were not
observed between CAP and CCAP patients9. In these
patient groups, anemia and leukocyte <15.000
mm3 were associated with prolonged fever and longer
hospitalization duration9.
In our study, no significant growth was observed in the blood cultures
of patients hospitalized due to CAP and CCAP. This was attributed to
peroral antibiotic use before hospitalization. Regardless of the
presence of pulmonary complications, the bacteremia incidence is low in
patients followed-up for pneumonia, and a possible pathogen is rarely
detected in the blood culture11,33. Neuman MI et al.
conducted a study in the USA in 2017. Results showed that a pathogenic
microorganism was detected in the blood culture in only 65 (2.5%) of
2568 patients hospitalized due to pneumonia33. In this
study, empirical antibiotic use before hospitalization less likely
caused growth in the blood culture33. In a
retrospective study conducted by Erlichman I et al., which included 144
children hospitalized due to CCAP, empirical antibiotics use before
hospitalization decreased the growth rate in the blood culture from 63%
to 22%. However, the pathogen proportion detected in pleural cultures
was higher34. In a 20-year retrospective study in the
USA, the blood culture growth rate decreased from 67% to 30% with
empirical antibiotic use before hospitalization in 369 patients who had
EMP35. In a study examining patients who were
followed-up for PPE and EMP between 2010 and 2017, the pathogen
proportion was significantly lower in the blood culture than in pleural
cultures33.
Viral and bacterial PCR amplification of samples collected from the
respiratory tract and pleura could not be obtained from each patient due
to technical problems. RSV was the most common viral agent detected.
Within the last 10 years, respiratory and pleural fluid DNA PCR
amplification methods, which can yield faster results than conventional
culture and are not affected by empirical antibiotic use, are commonly
used in pathogen identification9,20,36. The DNA PCR of
samples collected from pleural fluid can provide more sensitive results
than that of blood culture samples, and the serotyping results can be
obtained significantly faster36. However, there are
limitations in the differentiation of pathogenic microorganisms due to
colonization when nasopharyngeal, oropharyngeal, sputum samples are used37.
In our study, according to CT scan data, the antibiotic therapy type and
duration was modified and more detailed information could be obtained
before the surgical intervention, particularly in our patient with NP
and BPF. If fever does not subside within 72 h and the clinical
condition does not improve or worsens in patients followed-up for CAP,
treatment for CCAP should be modified, if necessary, according to the
evaluation results21,38. When CXR and thoracic USG are
not effective for the diagnosis of complications, such as BPF and
pneumatocele, particularly in the differentiation of NP and LA, more
detailed information can be obtained via CT scan22,38
In our study, pleural effusion >10 mm during admission is a
significant variable for CCAP diagnosis. Similar studies have shown that
the presence of pleural effusion at presentation is associated with CCAP
diagnosis9-11. In patients with unresolved
radiological and clinical findings, YCA, tuberculosis-related
lymphadenopathy, and congenital lung malformations may be observed.
In accordance with studies in the literature, our research showed that
CCAP patients commonly present with hypoxia upon admission, and oxygen
therapy was required during hospitalization. CCAP patients have a longer
hospitalization duration than CAP patients due to local and systemic
complications and the need for additional interventions (GT, CDF, and
VATS) during follow-up39. BPF was observed, with an
incidence rate of 13% in children with NP in the USA and 67% in
Brazil12,14. Patients followed-up for CCAP,
particularly NP and BPF with complications, had a longer
hospitalization, oxygen therapy, and fever duration and higher number of
PICU and even ECMO follow-ups16,40.
In our study, intravenous SAM and/or peroral macrolide were administered
to patients diagnosed with CAP, and treatment was modified when CCAP was
detected. The antibiotic duration and type used before admission were
not significant risk factors for CCAP development. In previous
retrospective studies and a prospective research conducted by Huang CY
et al., disease progression was observed regardless of the empirical
antibiotic therapy type provided according to the current treatment
guidelines10,15.
VATS is associated with better outcomes and shorter hospitalization
duration compared with pleural drainage with GT without
fibrinolytics20. In 2021, the American Academy of
Pediatric Surgery recommended that VATS should be considered when
chemical debridement with CDF cannot be achieved20. In
a systematic review and meta-analysis published in 2018, similar
perioperative complications were observed in cases in which both methods
were used. However, patients who received VATS were exposed to less
repetitive interventions and had a shorter hospitalization
duration41. Based on these data, in recent years,
studies about early VATS use, instead of CDF, in children have been
published in accordance with those in adults42. When
sufficient debridement with GT is not achieved and VATS is performed in
the early period before fibrinolytic use, the hospitalization duration
is shortened. Further, the complication incidence is lower in patients
treated with VATS than in those treated with CDF42.
Based on these developments, VATS is preferred instead of CDF when
adequate pleural fluid drainage cannot be achieved with thoracentesis
and GT implantation for PPE and EMP treatment in our hospital after
2017, which was the time our study was conducted.
The surgical intervention timing can affect treatment
success43,44. CDF can be used for early-stage disease
management. However, it is not effective for advanced-stage disease, and
complication incidence increases with repeated interventions including
CDF. Moreover, hospitalization duration is
prolonged43. VATS efficacy decreases, particularly
after 1 month, and decortication may be required in patients who
underwent CDF43-46. In relation to this, the European
Association for Cardio-Thoracic Surgery recommends that VATS should be
highly considered in all advanced-stage disease patients at
presentation46
The current study had several limitations. That is, the research was
retrospective in nature. Hence, antipyretic treatment use, content, and
frequency, as well as its effect on CCAP development, could not be
investigated because the patients’ family members did not regularly
follow-up for fever. Moreover, our hospital is a tertiary referral
center, and most patients had received prior treatment. However, late
referrals could affect outcomes. Although necessary, not all patients
could undergo respiratory and pleural DNA PCR amplification due to
technical problems.
In conclusion, pleural effusion,
respiratory distress (tachypnea and retraction), and hypoxia at
presentation were found to be independent risk factors for CAP.
Therefore, experience in interventional radiology and pediatric surgery
and use of multidisciplinary approaches may be important for the
diagnosis and treatment of children with CCAP admitted in tertiary care
centers. However, multicenter, prospective and comparative studies
should be conducted to examine CDF and VATS efficacy in children with
early- and late-stage diseases.