Krishnan Raghavendran
Presentation
A 28-year-old male was involved in a motor vehicular accident traveling at 60 miles per hour. He sustained a significant traumatic brain injury (Glasgow coma scale of eight), was intubated at site, and transported to the ED. Subsequent workup revealed multiple cerebral contusions with no midline shift, infiltrates in the base of the right lung zones, mild hypoxia, and a femur fracture. He was then admitted to the intensive care unit (ICU) and was managed with supportive care including monitoring of intracranial pressure, mechanical ventilation, early nutrition and appropriate prophylaxis for prevention of venous thromboembolism, and stress-related mucosal disease. On the fourth day following trauma, he had a fever of 101°F, a leukocytosis of 21,000, and a new-onset infiltrate in the right upper lobe.
Differential Diagnosis
Presence of fever, leukocytosis, and a new infiltrate in a patient who has been endotracheally intubated and mechanically ventilated should raise a strong suspicion for ventilator-associated pneumonia (VAP). The patient at the time of initial presentation had evidence of hypoxia with an infiltrate in the lung, and this should raise the possibility of aspiration-induced lung injury. Aspiration-induced pneumonitis may manifest signs similar to infection, but a major aspiration event is unlikely at a point where patient has been intubated with a cuffed tube. However, aspiration pneumonitis is a risk factor for development of aspiration pneumonia. Isolated pulmonary contusion without any other evidence of thoracic trauma is unlikely and is not likely to manifest fever and leukocytosis. Pulmonary infarctions secondary to pulmonary embolism should also be considered in the differential diagnosis. Finally, acute development of a dense infiltrate in the right upper lobe should also raise the possibility of migration of the endotracheal tube down the right main stem bronchus with resultant occlusion of the right upper lobe bronchus and subsequent collapse. However, a collapse is not associated with fever or leukocytosis.
VAP, defined as a pulmonary infection occurring after at least 48 hours of mechanical ventilation, is the leading cause of death in the ICU, with estimated prevalence rates of 10% to 65% and mortality rates of 25% to 60%. The incidence of VAP varies from series to series, and in general, the incidence varies from 5 to 25/1,000 ventilator days. VAP remains a major cause of mortality and morbidity in the critically ill patient and comprises the second commonest nosocomial infection in the ICU. In spite of significant advances that have been made in recent years to reduce the incidence of VAP in most ICUs, it still is considered the major cause of mortality and increased economic burden associated with the mechanically ventilated patient. The crucial aspect in the management of VAP relies on prompt and accurate diagnosis.
Workup
This patient underwent a bronchoscopy and quantitative bacteriology from the bronchoalveolar lavage (BAL). A Gram stain from the lavage was additionally obtained. A chest x-ray showed the tip of the endotracheal tube was visualized at 4 cm above the carina.
The timing or the clinical criteria used to diagnose VAP are variable. Most ICUs either follow the CDC criteria (fever, leukocytosis, and new-onset infiltrate) or a variation of clinical pulmonary infection score. The latter scoring system takes into consideration fever, leukocytosis, nature of tracheal secretions, lung infiltrate, and oxygenation with/without BAL Gram stain finding of neutrophils or bacteria. Once the clinical suspicion of VAP is entertained, a bacteriologic workup is then initiated.
Determination of specific bacteriology and early initiation of appropriate broad-spectrum antibiotics remain the cornerstone of diagnosis and treatment of VAP. Sputum Gram stain and culture are considered inappropriate, as they are neither sensitive nor specific. The specimen used for quantitative bacteriology should be obtained either through a bronchoscope or by the use of a coaxial catheter that is inserted blindly through the endotracheal tube. The latter approach, called the mini-BAL, does not involve a bronchoscope, and the diagnostic yield is considered similar to conventional bronchoscopy. Additionally, some ICUs use a protective brush inserted via a bronchoscope to obtain direct cultures from the affected area of the lung. The brush is then retrieved and directly plated onto the culture media. Significance is attributed to observed bacterial burden of more than 104 CFU/mL.
Diagnosis and Treatment
Regardless of the diagnostic modality used to ascertain the specific bacteriology, early initiation of appropriate broad-spectrum antibiotic therapy should be initiated as soon as the cultures are obtained. VAP is broadly classified into early (<4 ventilator days) and late (>4 ventilator days). The bacteriology of early VAP involves Enterobacteriaceae or gram-positive organisms such as methicillin-sensitive Staphylococcus aureus (MSSA). The appropriate antibiotic of choice includes second-generation cephalosporins, fluoroquinolones, or extended-spectrum penicillins as a single agent. Late VAP is invariably due to resistant organisms including but not limited to methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas species, or Acinetobacter species (Table 1). A combination therapy of vancomycin plus beta lactams (third-generation cephalosporins, carbapenems) or fluoroquinolones +/− aminoglycosides is recommended.
TABLE 1. Bacteriology of Isolated Organisms from a Single Center Study
With improved understanding of the pathogenesis of VAP, major strides have been taken in recent years in the institution of prevention strategies for VAP. A detailed list of methodologies used to prevent VAP and items included in the VAP bundle is provided in Table 2.
TABLE 2. Measures to Prevent VAP and Components of VAP Bundle
Case Conclusion
The patient was diagnosed with VAP on the fourth day following trauma. Patient was started on ceftriaxone at the time of diagnosis. The quantitative cultures were consistent with 105 CFU/mL of Klebsiella pneumoniae. The antibiotics were discontinued after 8 days at which time the white count and fever had subsided. The ventriculostomy catheters were removed on the sixth day following trauma and patient continued to improve clinically. He was extubated on the ninth posttrauma day and was subsequently transferred to an adult rehabilitation facility.
TAKE HOME POINTS
· The bacteriology of early and late VAP is very different and should inform antibiotic selection.
· It is important to obtain quantitative bacteriology from the lower respiratory tract prior to initiation of antibiotics.
· The initiation of antibiotics should be prompt and broad spectrum and also depend on typical microbiograms of the individual ICU.
· The duration of treatment should be 5–14 d.
· De-escalation or discontinuation of antibiotics should be considered once the quantitative cultures are finalized.
SUGGESTED READINGS
American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcareassociated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388–416.
Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002;165(7):867–903.
Iregui M, Ward S, Sherman G, et al. Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest. 2002;122(1): 262–268.
Kollef MH. Prevention of hospital-associated pneumonia and ventilator-associated pneumonia. Crit Care Med. 2004;32(6):1396–1405.
Raghavendran K, Wang J, Bellber C, et al. Predictive value of sputum gram stain for the determination of appropriate antibiotic therapy for VAP. J Trauma. 2007;62(6): 1377–1383.