eMedicine Specialties > Infectious Diseases > Bacterial Infections

Klebsiella Infections

Author: Obiamiwe Umeh, MBBS, Fellow, Center for AIDS Research and Education, David Geffen School of Medicine at UCLA
Coauthor(s): Leonard B Berkowitz, MD, Chief, Divisions of Infectious Diseases and HIV/AIDS Services, Brooklyn Hospital Center; Clinical Assistant Professor, Department of Medicine, State University of New York at Brooklyn
Contributor Information and Disclosures

Updated: May 15, 2009

Introduction

Background

The genus Klebsiella belongs to the tribe Klebsiellae, a member of the family Enterobacteriaceae. The organisms are named after Edwin Klebs, a 19th century German microbiologist. Klebsiellae are nonmotile, rod-shaped, gram-negative bacteria with a prominent polysaccharide capsule. This capsule encases the entire cell surface, accounts for the large appearance of the organism on gram stain, and provides resistance against many host defense mechanisms.

Members of the Klebsiella genus typically express 2 types of antigens on their cell surface. The first is a lipopolysaccharide (O antigen); the other is a capsular polysaccharide (K antigen). Both of these antigens contribute to pathogenicity. About 77 K antigens and 9 O antigens exist. The structural variability of these antigens forms the basis for classification into various serotypes. The virulence of all serotypes appears to be similar.

The genus was originally divided into 3 main species based on biochemical reactions. Today, 7 species with demonstrated similarities in DNA homology are known. These are (1) Klebsiella pneumoniae, (2) Klebsiella ozaenae, (3) Klebsiella rhinoscleromatis, (4) Klebsiella oxytoca, (5) Klebsiella planticola, (6) Klebsiella terrigena, and (7) Klebsiella ornithinolytica. K pneumoniae is the most medically important species of the group. K oxytoca and K rhinoscleromatis have also been demonstrated in human clinical specimens. In recent years, klebsiellae have become important pathogens in nosocomial infections.¹

Pathophysiology

Host defense against bacterial invasion depends on phagocytosis by polymorphonuclear granulocytes and the bactericidal effect of serum, mediated in large part by complement proteins. Both classic-pathway and alternate-pathway complement activation have been described, but the latter, which does not require the presence of immunoglobulins directed against bacterial antigens, appears to be the more active pathway in K pneumoniae infections.

Recent data from preclinical studies suggest a role for neutrophil myeloperoxidase and lipopolysaccharide-binding protein in host defense against K pneumoniae infection. Neutrophil myeloperoxidase is thought to mediate oxidative inactivation of elastase, an enzyme implicated in the pathogenesis of various tissue-destroying diseases. Lipopolysaccharide-binding protein facilitates transfer of bacterial cell wall components to inflammatory cells. Investigators showed higher rates of infection in experimental mice deficient in the genes that control expression of these 2 agents.

The bacteria overcome innate host immunity through several means. They possess a polysaccharide capsule, which is the main determinant of their pathogenicity. The capsule is composed of complex acidic polysaccharides. Its massive layer protects the bacterium from phagocytosis by polymorphonuclear granulocytes. In addition, the capsule prevents bacterial death caused by bactericidal serum factors. This is accomplished mainly by inhibiting the activation or uptake of complement components, especially C3b. The bacteria also produce multiple adhesins. These may be fimbrial or nonfimbrial, each with distinct receptor specificity. These help the microorganism to adhere to host cells, which is critical to the infectious process.

Lipopolysaccharides (LPS) are another bacterial pathogenicity factor. They are able to activate complement, which causes selective deposition of C3b onto LPS molecules at sites distant from the bacterial cell membrane. This inhibits the formation of the membrane attack complex (C5b-C9), which prevents membrane damage and bacterial cell death.

Availability of iron increases host susceptibility to K pneumoniae infection. Bacteria are able to compete effectively for iron bound to host proteins because of the secretion of high-affinity, low molecular weight iron chelators known as siderophores. This is necessary because most host iron is bound to intracellular and extracellular proteins. In order to deprive bacteria of iron, the host also secretes iron-binding proteins.

Epidemiology

Klebsiellae are ubiquitous in nature. In humans, they may colonize the skin, pharynx, or gastrointestinal tract. They may also colonize sterile wounds and urine. Carriage rates vary with different studies. Klebsiellae may be regarded as normal flora in many parts of the colon and intestinal tract and in the biliary tract. Oropharyngeal carriage has been associated with endotracheal intubation, impaired host defenses, and antimicrobial use.

K pneumoniae and K oxytoca are the 2 members of this genus responsible for most human infections. They are opportunistic pathogens found in the environment and in mammalian mucosal surfaces. The principal pathogenic reservoirs of infection are the gastrointestinal tract of patients and the hands of hospital personnel. Organisms can spread rapidly, often leading to nosocomial outbreaks.

Infection with Klebsiella organisms occurs in the lungs, where they cause destructive changes. Necrosis, inflammation, and hemorrhage occur within lung tissue, sometimes producing a thick, bloody, mucoid sputum described as currant jelly sputum. The illness typically affects middle-aged and older men with debilitating diseases such as alcoholism, diabetes, or chronic bronchopulmonary disease. This patient population is believed to have impaired respiratory host defenses. The organisms gain access after the host aspirates colonizing oropharyngeal microbes into the lower respiratory tract.

Klebsiellae have also been incriminated in nosocomial infections. Common sites include the urinary tract, lower respiratory tract, biliary tract, and surgical wound sites. The spectrum of clinical syndromes includes pneumonia, bacteremia, thrombophlebitis, urinary tract infection (UTI), cholecystitis, diarrhea, upper respiratory tract infection, wound infection, osteomyelitis, and meningitis. The presence of invasive devices, contamination of respiratory support equipment, use of urinary catheters, and use of antibiotics are factors that increase the likelihood of nosocomial infection with Klebsiella species. Sepsis and septic shock may follow entry of organisms into the blood from a focal source.

Rhinoscleroma and ozena are 2 other infections caused by Klebsiella species. These diseases are rare. Rhinoscleroma is a chronic inflammatory process involving the nasopharynx, whereas ozena is a chronic atrophic rhinitis characterized by necrosis of nasal mucosa and mucopurulent nasal discharge.

K oxytoca has been implicated in neonatal bacteremia, especially among premature infants and in neonatal intensive care units. Increasingly, the organism is being isolated from patients with neonatal septicemia.

Extensive use of broad-spectrum antibiotics in hospitalized patients has led to both increased carriage of klebsiellae and, subsequently, the development of multidrug-resistant strains that produce extended-spectrum beta-lactamase (ESBL). These strains are highly virulent, show capsular type K55, and have an extraordinary ability to spread. Most outbreaks are due to a single clone or single gene; the bowel is the major site of colonization with infection of the urinary tract, respiratory tract, and wounds. Bacteremia and significant increased mortality have resulted from infection with these species.

In addition to prior antibiotic use, risk factors for infection include the presence of an indwelling catheter, feeding tube, or central venous catheter; poor health status; and treatment in an intensive care unit or nursing home. Acquisition of these species has become a major problem in most hospitals because of resistance to multiple antibiotics and potential transfer of plasmids to other organisms.

Frequency

United States

In some parts of the world, K pneumoniae is an important cause of community-acquired pneumonia in elderly persons. Studies conducted in Malaysia and Japan estimate the incidence rate in elderly persons to be 15-40%, which is equal to, if not greater than, that of Haemophilus influenzae. However, in the United States, these figures are different. Persons with alcoholism are the main population at risk, and they constitute 66% of people affected by this disease. Mortality rates are as high as 50% and approach 100% in persons with alcoholism and bacteremia.

Klebsiellae are also important in nosocomial infections among adult and pediatric populations. Klebsiellae account for approximately 8% of all hospital-acquired infections. In the United States, depending on the study reviewed, they comprise 3-7% of all nosocomial bacterial infections, placing them among the top 8 pathogens in hospitals. Klebsiellae cause as many as 14% of cases of primary bacteremia, second only to Escherichia coli as a cause of gram-negative sepsis. They may affect any body site, but respiratory infections and UTIs predominate.

Of 145 reported epidemic outbreaks of nosocomial bacteremias during 1983-1991, 13 were attributed to Klebsiella organisms. The US Centers for Disease Control and Prevention report that Klebsiella strains were responsible for 3% of all pathogenic epidemic outbreaks.

K oxytoca is among the top 4 pathogens that cause infection in patients in neonatal intensive care units. It is the second most frequent cause of gram-negative neonatal bacteremia.

International

Outbreaks of neonatal septicemia occur worldwide. Infection with K pneumoniae also has a worldwide distribution. Infection with K rhinoscleromatis is not common in the United States, although it has a worldwide distribution and is usually observed in areas of eastern Europe, southern Asia, central Africa, and Latin America.

Mortality/Morbidity

• Klebsiella pneumonia is a necrotizing process with a predilection for debilitated people. It has a high mortality rate of approximately 50% even with antimicrobial therapy. The mortality rate approaches 100% for persons with alcoholism and bacteremia.
• Klebsiella bacteremia and sepsis produce clinical manifestations similar to those caused by other gram-negative enteric organisms. Morbidity and mortality rates are comparable to those for other gram-negative organisms that cause sepsis and septic shock. In neonatal units, outbreaks caused by ESBL-producing strains present a more serious problem and may be associated with increased mortality.

Age

• Community-acquired Klebsiella (Friedlãnder) pneumonia is a disease of debilitated middle-aged and older men with alcoholism.
• Nosocomial infections may affect adults or children, and they occur more frequently in premature infants, patients in neonatal intensive care units, and hospitalized individuals who are immunocompromised.

Clinical

History

• Community-acquired pneumonia
  • Lobar pneumonia differs from other pneumonias in that it is associated with destructive changes in the lungs. It is a very severe illness with a rapid onset and often-fatal outcome despite early and appropriate antimicrobial treatment.
  • Patients typically present with an acute onset of high fever and chills; flulike symptoms; and productive cough with an abundant, thick, tenacious, and blood-tinged sputum sometimes called currant jelly sputum.
  • An increased tendency exists toward abscess formation, cavitation, empyema, and pleural adhesions.
  • Most pulmonary diseases caused by K pneumoniae are in the form of bronchopneumonia or bronchitis. These infections are usually hospital-acquired and have a more subtle presentation.
• Urinary tract infection²
  • Klebsiellae UTIs are clinically indistinguishable from UTIs caused by other common organisms.
  • Clinical features include frequency, urgency, dysuria, hesitancy, low back pain, and suprapubic discomfort. Systemic symptoms such as fever and chills are usually indicative of a concomitant pyelonephritis or prostatitis.
• Nosocomial infection
  • Important manifestations of klebsiellae infection in the hospital setting include UTI, pneumonia, bacteremia, wound infection, cholecystitis, and catheter-associated bacteriuria. The presence of invasive devices in hospitalized patients greatly increases the likelihood of infection. Patients with these infections have similar presentations to those with infections caused by other organisms.
  • Other nosocomial infections in which klebsiellae may also be implicated include cholangitis, meningitis, endocarditis, and bacterial endophthalmitis. The latter occurs especially in patients with liver abscesses³ and diabetes. These infectious presentations are relatively uncommon.
• Rhinoscleroma and ozena
  • K rhinoscleromatis and K ozaenae cause rhinoscleroma and ozena, respectively. Both are rare in the United States and are associated with upper respiratory infection.
  • Rhinoscleroma is a chronic granulomatous infection. Patients present with a purulent nasal discharge with crusting and nodule formation that leads to respiratory obstruction. Diagnosis is aided by histology findings and positive results from blood culture.
  • Ozena is a primary atrophic rhinitis that often occurs in elderly persons. Common symptoms include nasal congestion and a constant nasal bad smell. Patients also may complain of headache and symptoms attributable to chronic sinusitis. Unlike rhinoscleroma, nasal congestion is not a prominent feature.
• Colonization
  • Differentiating nosocomial colonization from infection presents a formidable challenge in clinical practice. It is a common problem in patients with indwelling catheters.
  • Duration of catheterization is the most important risk factor for the development of bacteriuria. Keeping catheter systems closed and removing catheters as soon as possible are ways to prevent development of bacteriuria.
  • Most catheter-related UTIs are asymptomatic; the usual complaints of frequency, urgency, dysuria, hesitancy, low back pain, and suprapubic discomfort typically are absent. Therefore, demonstration of bacteriuria is necessary to make a diagnosis. A density of 100,000 colony-forming units per milliliter is usually required to make a diagnosis. Concomitant presence of pyuria is usually present in patients with catheter-associated infection as opposed to those with colonization.
  • In general, the presence of symptoms in conjunction with bacteriological evidence of infection helps distinguish infection, in which organisms cause disease, from colonization, in which organisms coexist without causing harm.

Physical

• Klebsiella pneumonia characteristically affects one of the upper lobes of the lung, although infection of the lower lobes is not uncommon.
• Examination of patients with community-acquired pneumonia usually reveals unilateral chest signs, predominantly in the upper lobes. When these signs are observed in a patient such as described in History, the diagnosis of Klebsiella pneumonia is strongly suggested.
• Clinical signs observed in patients with extrapulmonary disease depend on the organ system involved. In cases of nosocomial infections, physical examination should include a search for factors that predispose the individual to the development of such infections. These should include inspection for the presence and duration of invasive devices, wounds, and burn sites.

Causes

• Host factors that lead to colonization and infection include the following:
  • Hospitalization (especially admission to an intensive care unit)
  • Immunocompromised states (eg, diabetes, alcoholism)
  • Antimicrobial therapy
  • Prolonged use of invasive medical devices
  • Inadequate infection control practices
  • Severe illness, including major surgery
• The organism gains access to the body either by direct inoculation through breached epithelial surfaces or following aspiration of oropharyngeal organisms.

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