As with other atypical organisms, C. pneumoniae can be treated with doxycycline, a macrolide, or respiratory fluoroquinolones. However, length of therapy varies by regimen used; whereas treating with doxycycline 100 mg twice daily generally requires 14–21 days, moxifloxacin 400 mg daily only requires 10 days [49].
M. pneumoniae
As with C. pneumoniae, length of therapy of M. pneumoniae varies by antimicrobial used. Shortest courses are seen with the use of macrolides for 5 days, whereas 14 days is considered standard for doxycycline or a respiratory fluoroquinolone [50]. It should be noted that there has been increasingly documented resistance to macrolides, with known resistance of 8.2% in the United States [51].
Duration of Treatment
Most patients with CAP respond within 72 hours to appropriate therapy. IDSA/ATS guidelines recommend that patients be treated for a minimum of 5 days, and before discontinuing antibiotics patients should be afebrile a minimum of 48-72 hours and be clinically stable (Table 6) [16].
The recommended minimum 5 days of therapy is valid for routine cases of CAP. Despite this, a majority of patients are treated for an excessive amount of time, with over 70% of patients reported to have received over 10 days for uncomplicated CAP [52]; however, there are instances that require longer courses of antibiotics (eg, cases caused by P. aeruginosa, S. aureus, Legionella spp; patients with lung abscesses or necrotizing infections, among others) [53]. CRP has been postulated as an additional measure of stability, specifically monitoring for > 50% reduction in CRP; however, this was validated only for those with complicated pneumonia [54].
Hospitalized patients do not need to be monitored for an additional day once they have reached clinical stability (Table 6), are able to maintain oral intake, and have normal mentation, provided that other comorbidities are stable and social needs have been met [16]. Patients discharged from the hospital with instability have higher risk of readmission or death [55].
Transition to Oral Therapy
IDSA/ATS guidelines [16] recommend that patients should be transitioned from IV to oral antibiotics when they are improving clinically, have stable vital signs, and are able to ingest food/fluids and medications.
Management of Nonresponders
Although the majority of patients respond to antibiotics within 72 hours, treatment failure occurs in up to 15% of patients [45]. Nonresponding pneumonia is generally seen in 2 patterns: worsening of clinical status despite empiric antibiotics OR delay in achieving clinical stability as defined in Table 5 after 72 hours of treatment [13]. Risk factors associated with nonresponding pneumonia [56] are:
Bacteriologic: MRSA, gram-negative or Legionella pneumonia
Severity index: PSI > 90
Pharmacologic: incorrect antibiotic choice based on susceptibility
Patients with acute deterioration of clinical status will prompt transfer to a higher level of care and may require mechanical ventilator support. In those with delay in achieving clinical stability, question centers on whether the same antibiotics can be continued while doing further radiographic/microbiologic workup and/or changing antibiotics.
History should be reviewed with particular attention to exposures, travel history, and microbiologic and radiographic data. Clinicians should recall that viral causes account for up to 20% of pneumonias and there are also noninfectious causes that can mimic pyogenic infections [57]. If adequate initial cultures were not obtained, they should be obtained; however, care must be taken in reviewing new sets of cultures while on antibiotics as they may reveal colonization selected out by antibiotics and not a true pathogen. If repeat evaluation is unrevealing, then further evaluation with CT scan and bronchoscopy with bronchoalveolar lavage and biopsy is warranted. CT scans can show pleural effusions, bronchial obstructions or pattern suggestive of cryptogenic pneumonia. A bronchoscopy might yield a microbiologic diagnosis and with biopsy can also evaluate for noninfectious causes.
As with other infections, if escalation of antibiotics is undertaken, clinicians should be mindful to ensure that efforts are being made to elucidate the reason for nonresponse. To simply broaden antimicrobial therapy without attempts at establishing a microbiologic or radiographic cause for nonresponse may lead to inappropriate treatment recurrence of infection. Aside from patients who have bacteremic pneumococcal pneumonia in an ICU setting, there are no published reports pointing to superiority of combination antibiotics [46].
Other Treatment
Because of the inflammatory response associated with pneumonia, several agents have been evaluated as adjunctive treatment of pneumonia to decrease this inflammatory state; namely, steroids, macrolide antibiotics and statins. To date, only the use of steroids (methylprednisolone 0.5 mg/kg every 12 hours for 5 days) in those with severe CAP and high initial anti-inflammatory response (CRP > 150) was shown to decrease treatment failure, decreased risk of ARDS, possibly reduce length of stay, duration of intravenous antibiotics and clinical stability, without effect on mortality or adverse side effects [58,59].
