Klebsiella Pneumonia

Etiology

Klebsiella pneumoniae belongs to the Enterobacteriaceae family and is described as a gram-negative, encapsulate, and non-motile bacterium. Virulence of the bacterium is provided by a wide array of factors that can lead to infection and antibiotic resistance. The polysaccharide capsule of the organism is the most important virulence factor and allows the bacteria to evade opsonophagocytosis and serum killing by the host organism. To date, 77 different capsular types have been studied, and those Klebsiella species without a capsule tend to be less virulent. A second virulence factor is lipopolysaccharides that coat the outer surface of a gram-negative bacteria. The sensing of lipopolysaccharides releases an inflammatory cascade in the host organism and has been a major culprit of the sequela in sepsis and septic shock. Another virulence factor, fimbriae, allows the organism to attach itself to host cells. Siderophores are another virulence factor that is needed by the organism to cause infection in hosts. Siderophores acquire iron from the host to allow propagation of the infecting organism.[3][4]

Klebsiella pneumoniae is one of a handful of bacteria that are now experiencing a high rate of antibiotic resistance secondary to alterations in the core genome of the organism. Alexander Fleming first discovered resistance to beta-lactam antibiotics in 1929 in gram-negative organisms. Since that time, K. pneumoniae has been well studied and has been shown to produce a beta-lactamase that causes hydrolysis of the beta-lactam ring in antibiotics. Extended-spectrum beta-lactamase (ESBL) K. pneumoniae was seen in Europe in 1983 and the United States in 1989. ESBLs can hydrolyze oxyimino cephalosporins rendering third-generation cephalosporins ineffective against treatment. Due to this resistance, carbapenems became a treatment option for ESBL. However, of the 9000 infections reported to the Centers for Disease Control and Prevention (CDC) due to carbapenem-resistant Enterobacteriaceae in 2013, approximately 80% were due to K. pneumoniae. Carbapenem resistance has been linked to an up-regulation in efflux pumps, alteration of the outer membrane, and increased production of ESBL enzymes in the organism.

Epidemiology

Humans serve as the primary reservoir for K. pneumoniae. In the general community, 5% to 38% of individuals carry the organism in their stool and 1% to 6% in the nasopharynx. The main reservoirs of infection are the patient's gastrointestinal tract and the hands of hospital personnel. It can lead to a nosocomial outbreak. However, higher rates of colonization have been reported in those of Chinese ethnicity and those who experience chronic alcoholism. In hospitalized patients, the carrier rate for K. pneumoniae is much higher than that in the community. In one study, carrier rates as high as 77% can be seen in the stool of those hospitalized and are related to the number of antibiotics given.[5][6]

Pneumonia caused by K. pneumoniae can be broken down into community-acquired or hospital-acquired pneumonia. Although community-acquired pneumonia is a fairly common diagnosis, infection with K. pneumoniae is uncommon. In Western culture, it is estimated that approximately 3% to 5% of all community-acquired pneumonia is related to an infection caused by K. pneumoniae, but in developing countries such as Africa, it can account for approximately 15% of all cases of pneumonia. Overall, K. pneumoniae accounts for approximately 11.8% of all hospital-acquired pneumonia in the world. In those who develop pneumonia while on a ventilator, between 8% to 12% are caused by K. pneumoniae, while only 7% occur in those patients who are not ventilated. Mortality ranges from 50% to 100% in patients with alcoholism and septicemia.

Pathophysiology

Host protection from bacterial invasion mainly depends on two things: polymorphonuclear granulocytes, which phagocytose the bacteria, and serum complement proteins, which are bactericidal. The alternate pathway of complement activation is more active in Klebsiella pneumoniae infection. Neutrophil myeloperoxidase and lipopolysaccharide-binding protein facilitate in defense against Klebsiella pneumoniae infection.

Bacteria have a polysaccharide capsule made up of complex acidic polysaccharides and determine their pathogenicity. The capsule protects bacteria from phagocytosis and serum bactericidal proteins. It adheres to host cells with many fimbrial and non-fimbrial adhesions, which is critical to the infectious process.

History and Physical

The presentation of pneumonia caused by K. pneumoniae is similar to that seen in community-acquired pneumonia. Patients may have a cough, fever, pleuritic chest pain, and shortness of breath. One stark difference between community-acquired pneumonia caused by Streptococcus pneumoniae and K. pneumoniae is the type of sputum produced. The sputum produced by those with S. pneumoniae is described as “blood-tinged” or “rust-colored,” however, the sputum produced by those infected by K. pneumoniae is described as “currant jelly.” The reason for this is that K. pneumoniae results in significant inflammation and necrosis of the surrounding tissue.

Klebsiella pneumonia usually affects the upper lobes but can involve the lower lobes as well. The examination usually reveals unilateral signs of consolidation, such as crepitation, bronchial breathing, and increased vocal resonance, mostly in the upper lobe. In the case of nosocomial infections, the presence of burn sites, wounds, and invasive devices should be searched. 

Host factors that predispose to colonization and infection are as follows:

• Admission to an intensive care ward
• Prolonged use of invasive devices
• Poor infection control strategies
• Immunocomproside especially alcoholics and diabetics
• Prolonged use of broad-spectrum antibiotics

Bacteria enter the host either by direct inoculation or by following oropharyngeal aspiration.

Evaluation

Laboratory analysis will typically show leukocytosis, and this alone is unable to aid the clinician in diagnosing the organism that caused a patient’s pneumonia. Chest radiographs, however, can aid the physician in narrowing their differential diagnosis to include K. pneumoniae as a cause for the patient’s condition. Pneumonia caused by K. pneumoniae typically causes a lobar infiltrate in the posterior aspect of the right upper lung. K. pneumoniae infections rarely cause lung abscesses in those with pneumonia but can commonly be associated with empyema. Another non-specific sign of K. pneumoniae on a chest radiograph is the bulging fissure sign. This is related to the large amount of infection and inflammation that the organism can cause. Although these findings can be used to aid the clinician in narrowing their differential diagnosis, they should not be thought of as indicative of pneumonia caused by K. pneumoniae. In the setting of pneumonia, infection with K. pneumoniae is confirmed by either sputum culture analysis or blood culture analysis.[7][8]

Treatment / Management

Given the low occurrence of K. pneumoniae in the community, the treatment of pneumonia should follow standard guidelines for antibiotic therapy. Once infection with K. pneumoniae is either suspected or confirmed, antibiotic treatment should be tailored to local antibiotic sensitivities. Current regimens for community-acquired K. pneumoniae pneumonia include a 14-day treatment with either a third or fourth-generation cephalosporin as monotherapy or a respiratory quinolone as monotherapy or either of the previous regimes in conjunction with an aminoglycoside. If the patient is penicillin-allergic, then a course of aztreonam or a respiratory quinolone should be undertaken. For nosocomial infections, a carbapenem can be used as monotherapy until sensitivities are reported.[9][10][11](B3)

When ESBL is diagnosed, carbapenem therapy should be initiated due to its rate of sensitivity across the globe. When CRE (carbapenem-resistant Enterobacteriaceae) is diagnosed, infectious disease consultation should be obtained to guide treatment. Several antibiotic options to treat CRE include antibiotics from the polymyxin class, tigecycline, fosfomycin, aminoglycosides, or dual therapy carbapenems. Combination therapy of two or more of the agents, as mentioned earlier, may decrease mortality as compared to monotherapy alone.

Differential Diagnosis

The differential diagnosis for pneumonia caused by K. pneumoniae should include;

• All organisms that typically cause community-acquired and hospital-acquired pneumonia, such as Staphylococcus, Pneumococcus, Pseudomonas, Acinetobacter, and Legionella.
• Tuberculosis
• Aspergillus infection
• Malignancy
• Acute respiratory distress syndrome (ARDS)
• Lung abscess
• Empyema and other pleuropulmonary infections

Surgical Oncology

Surgical debridement or drainage is sometimes required in patients with lung abscess, empyema, and lung gangrene.

Prognosis

The prognosis of Klebsiella pneumonia is poor, especially in patients who have alcohol use disorder, diabetes mellitus, nosocomial infection, or septicemia. Mortality from this type of pneumonia is above 50%.

Complications

Pneumonia caused by K. pneumoniae can be complicated by bacteremia, lung abscesses, and the formation of an empyema.