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Infectious Diseases > MEDICAL TOPICS
Klebsiella Infections
Article Last Updated: Apr 27, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 10
Author: Obiamiwe Umeh, MBBS, Fellow, Center for AIDS Research and Education, David Geffen School of Medicine at UCLA
Obiamiwe Umeh is a member of the following medical societies: American College of Physicians and American Medical Association
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
Editors: David Hall Shepp, MD, Program Director, Fellowship in Infectious Diseases, Department of Medicine, North Shore University Hospital; Associate Professor, New York University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; John W King, MD, Professor of Medicine, Section of Infectious Diseases, Louisiana State University Health Sciences Center; Director, Viral Therapeutics Clinics for Hepatitis; Consulting Staff, Department of Infectious Diseases, Overton Brook Veterans Affairs Medical Center; Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital; Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Author and Editor Disclosure
Synonyms and related keywords:
Klebsiella pneumoniae, K pneumoniae, Klebsiella ozaenae, K ozaenae, Klebsiella rhinoscleromatis, K rhinoscleromatis, Klebsiella oxytoca, K oxytoca, Klebsiella planticola, K planticola, Klebsiella terrigena, K terrigena Klebsiella ornithinolytica, K ornithinolytica, community-acquired pneumonia, CAP, nosocomial infection, urinary tract infection, rhinoscleroma, ozena, colonization, extended-spectrum beta-lactamase, ESBL, neonatal septicemia, neonatal bacteremia, bronchopneumonia, bronchitis, catheter-associated bacteriuria, lung infection
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.
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 (Friedländer) 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.
History
Klebsiellae cause a variety of clinical syndromes. Common klebsiellae infections in humans include (1) community-acquired pneumonia, (2) UTI, (3) nosocomial infection, (4) rhinoscleroma and ozena, and (5) colonization.
- 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 infection
- 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 abscesses 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.
Other Problems to be Considered
Community-acquired pneumonia
Staphylococcal pneumonia (see Staphylococcal Infections)
Pneumococcal pneumonia (see Pneumococcal Infections)
Legionellosis
Pleuropulmonary empyema (see Empyema, Pleuropulmonary)
Lung Abscess
Urinary tract infection
Urinary Tract Infection, Females
Urinary Tract Infection, Males
Pseudomonas infection (see Pseudomonas Aeruginosa Infections)
Cholecystitis
Nosocomial infection
Pseudomonas infection (see Pseudomonas Aeruginosa Infections)
Acinetobacter infection (see Acinetobacter)
Serratia infection (see Serratia)
Rhinoscleroma and ozena
Pseudomonas mallei infection (rare in humans) (see Pseudomonas Infection)
Viral rhinitis (eg, rhinovirus infection) (see Rhinoviruses)
Lab Studies
- A complete blood cell count usually reveals leukocytosis with a left shift, but this is not invariably present. Persistence of leukocytosis may signify empyema formation.
- Obtain a sputum sample for Gram stain. Klebsiellae appear as short, plump, gram-negative bacilli. They are usually surrounded by a capsule that appears as a clear space.
- Serology results are not useful for detection of infection with Klebsiella organisms.
- Cultures should be obtained from possible sites (eg, wounds, peripheral or central intravenous access sites, urinary catheters, respiratory support equipment).
- Klebsiellae may be isolated from blood, urine, pleural fluid, and wounds.
- Klebsiellae are microaerophilic and, thus, can grow in the presence of oxygen or in its absence. They have no special culture requirements. Most species can use citrate and glucose as sole carbon sources; thus, they grow well on most ordinary media.
- Klebsiellae are lactose-fermenting, urease-positive, and indole-negative organisms, although K oxytoca and some strains of K pneumoniae are exceptions. Klebsiellae do not produce hydrogen sulfide, and they yield positive results on both Voges-Proskauer and methyl red tests.
- Wounds may be infected with Klebsiella organisms as the sole pathogens or as a component of a multipathogenic infection. Swabs for Gram stain and culture taken from possible sites may aid in establishing the diagnosis.
Imaging Studies
- Chest radiography
- The organism usually involves one of the upper lobes; however, involvement of lower lobes is not uncommon.
- The affected lobe typically appears swollen, producing the bulging fissure sign. This presentation is not necessarily exclusive to Klebsiella infection. Other organisms, such as H influenzae, may produce a similar radiographic appearance.
- Cavitation, especially in the presence of a unilateral necrotizing pneumonia, strongly supports the possibility of a Klebsiella organism as the etiologic agent.
- Pleural effusion, empyema, abscess formation, and pleural adhesions occur with increased frequency in patients with Klebsiella pneumonia.
- Chest tomography
- Chest tomography may be required for patients with nonresolving or slowly responding cases of pneumonia.
- The findings from this imaging test help exclude entities that are treatable with drainage or debridement such as empyema and respiratory tract obstruction caused by K rhinoscleromatis infection.
Other Tests
- Susceptibility testing for ESBL-producing organisms
- The rising importance of ESBL-producing organisms has mandated effective screening methods for their detection. Use of aztreonam or ceftazidime resistance as a marker misses approximately 15-20% of ESBL-producing organisms. Resistance to cefpodoxime as a screening method, with sensitivity breakpoints of >2 mcg/mL by minimal inhibitory concentration or <22 mm by disk diffusion (for a 30-mcg cefpodoxime disk), has a sensitivity of at least 98% for ESBL detection.
- Different tests that help confirm ESBL susceptibility are available. One test involves using disks that contain cefotaxime and ceftazidime alone and disks containing a combination of clavulanic acid with these antibiotics. These are placed on Mueller-Hinton agar. A positive test result is defined as a 5-mm or greater increase in the size of the zone diameter for either cefotaxime or ceftazidime tested in combination with clavulanic acid versus the zone for either antibiotic tested alone. Another method is the E-test screen, which evaluates third-generation cephalosporins with and without a beta-lactamase inhibitor. Finally, the Vitek ESBL test, which is an automated broth microdilution test, uses cefotaxime and ceftazidime alone and in combination with clavulanic acid.
- A good screening strategy might include a cefpodoxime screen followed by confirmatory disk diffusion for screen-positive isolates. The Vitek test has sensitivity of at least 99.5% and specificity of 100%. It is a reliable single-test alternative.
Procedures
- Diagnostic thoracocentesis may be performed if a pleural fluid pocket is large enough for aspiration.
- Bronchoalveolar lavage with fiberoptic bronchoscopy may be helpful in occasional cases in which the diagnosis cannot be made by other means and can be used to ascertain the microbial organisms involved.
Medical Care
- Antibiotic selection
- Klebsiella organisms are resistant to multiple antibiotics. This is thought to be a plasmid-mediated property. Length of hospital stay and performance of invasive procedures are risk factors for acquisition of these strains.
- Treatment depends on the organ system involved. In general, initial therapy of patients with possible bacteremia is empirical. The choice of a specific antimicrobial agent depends on local susceptibility patterns. Once bacteremia is confirmed, treatment may be modified.
- Agents with high intrinsic activity against K pneumoniae should be selected for severely ill patients. Examples of such agents include third-generation cephalosporins (eg, cefotaxime, ceftriaxone), carbapenems (eg, imipenem/cilastatin), aminoglycosides (eg, gentamicin, amikacin), and quinolones. These agents may be used as monotherapy or combination therapy. Some experts recommend using a combination of an aminoglycoside and a third-generation cephalosporin as treatment for non–ESBL-producing isolates. Others disagree and recommend monotherapy.
- Aztreonam may be used in patients who are allergic to beta-lactam antibiotics. Quinolones are also effective treatment options for susceptible isolates in patients with either carbapenem allergy or major beta-lactam allergy.
- Other antibiotics used to treat susceptible isolates include ampicillin/sulbactam, piperacillin/tazobactam, ticarcillin/clavulanate, ceftazidime, cefepime, levofloxacin, norfloxacin, gaitfloxacin, moxifloxacin, meropenem, and ertapenem.
- Treatment of Klebsiella pneumonia has discrepant results. For patients with severe infections, a clinically prudent approach is the use of an initial short course (48-72 h) of combination therapy with an aminoglycoside, followed by a switch to an extended-spectrum cephalosporin when susceptibility is confirmed and ESBL production is excluded. The carbapenems are preferred for ESBL-producing strains.
- Community-acquired pneumonia
- The mortality rate may be 50%, regardless of treatment.
- Effective treatment for this rare condition consists of empirical coverage for gram-negative organisms, aggressive ventilation, and supportive care.
- Other measures include clinical and radiologic surveillance for surgically treatable entities such as pulmonary gangrene, lung abscess, and empyema.
- Third-generation cephalosporins or quinolones provide coverage for community-acquired K pneumoniae infection. In one study, combination therapy with aminoglycosides was shown to be superior; this benefit was not observed in other studies. Macrolides have no useful activity against K pneumoniae.
- Antibiotic therapy should be implemented for at least 14 days.
- Nosocomial K pneumoniae pneumonia
- Choose antibiotics with high intrinsic activity. A regimen that includes imipenem, third-generation cephalosporins, quinolones, or aminoglycosides may be used alone or in combination. Always confirm susceptibility. Treatment should last at least 14 days.
- If response is slow, chest tomography scans may be useful in helping exclude entities that are treatable with debridement or drainage.
- In patients who rapidly respond to intravenous therapy, switching to an oral quinolone is regarded as safe so long as the isolate is susceptible.
- K pneumoniae UTI
- Uncomplicated cases caused by susceptible strains may be treated with most oral agents except ampicillin. Monotherapy is effective, and therapy for 3 days is sufficient.
- Complicated cases may be treated with oral quinolones or with intravenous aminoglycosides, imipenem, aztreonam, third-generation cephalosporins, or piperacillin/tazobactam. Duration of treatment is usually 14-21 days. Intravenous agents are used until the fever resolves.
- Other measures may include correction of an anatomical abnormality or removal of a urinary catheter.
- Other K pneumoniae infections
- Combination therapy with a beta-lactam antibiotic and an aminoglycoside is considered the standard for empiric treatment of cholangitis. Few comparative data exist to establish this as the optimal therapy.
- Ciprofloxacin monotherapy is as effective as combination therapy for acute suppurative cholangitis. Antimicrobials are administered for at least 10 days. Biliary decompression may be required.
- Klebsiella meningitis in adults is rare. Nosocomial disease complicates shunts in children. Third-generation cephalosporins are the drugs of choice because of superior central nervous system penetration. Reports indicate success with cefotaxime, and meropenem is a useful alternative. Adjunctive measures include removal of infected shunts. The suggested duration of treatment is 3 weeks because higher relapse rates have been noted in patients treated with shorter courses of therapy.
- Klebsiella endophthalmitis and endocarditis are rare. Therapy for endophthalmitis may be intravitreal, intravenous, or both. Clinical experience is greatest with intravenous ceftazidime and aminoglycosides; however, intravenous therapy alone results in very poor drug levels at the site of infection. Endocarditis has been treated with a combination of an intravenous aminoglycoside and a beta-lactam antibiotic. Few data exist to guide treatment duration; however, 6 weeks of antibiotic therapy is considered reasonable.
- Infection with other Klebsiella species
- Antibiotic susceptibility and treatment guidelines for K oxytoca infection are virtually identical to those for K pneumoniae. In one study of very ill patients, K oxytoca bacteremia had a 21% mortality rate at 14 days.
- Rhinoscleroma is treated with combination antimicrobial therapy for 6-8 weeks. Therapeutic choices include aminoglycosides, tetracycline, sulfonamides, rifampin, and quinolones.
- Ozena may be treated with a 3-month course of ciprofloxacin. Intravenous aminoglycosides and trimethoprim/sulfamethoxazole are also useful in the treatment of these conditions. Susceptibility testing is usually required.
Surgical Care
- Surgery is required if drainage or debridement is necessary (eg, empyema, lung abscess, pulmonary gangrene, respiratory tract obstruction following persistent K rhinoscleromatis infection).
- Surgery may also be needed to correct underlying anatomical abnormalities that predispose patients to infection. An example is correction of posterior urethral valves in patients with recurrent UTIs. Cosmesis is another reason patients require surgical care. This is observed in deforming K rhinoscleroma infection.
- Thoracotomy with tube placement is required for empyema.
- Pleural decortication is a therapeutic option for persistent pleural adhesions, and extensive lung necrosis may require surgical resection.
Consultations
Surgical consultation is required for the conditions discussed in Surgical Care.
The following is a discussion on the specific agents used in the antimicrobial therapy of Klebsiella infections. In vitro data show that a wide range of beta-lactams, aminoglycosides, quinolones, and other antibiotics are useful for treatment of klebsiellae infections.
Cephalosporins have been widely used as monotherapy and in combination with aminoglycosides. Cephalosporins should be avoided if ESBL strains are present. In such instances, the carbapenems, especially imipenem, are effective.
Aztreonam and quinolones are useful in patients allergic to penicillin, and rifampin has been used for treatment of rhinoscleroma. TMP/SMZ is not used in primary treatment of pneumonia. They may be used as initial treatment in uncomplicated UTI and as second-line agents for ozena.
Drug Category: Antibiotics
Therapy must cover all likely pathogens in the context of this clinical setting. Antibiotic selection should be guided by culture and sensitivity results whenever feasible.
| Drug Name | Cefotaxime (Claforan) |
| Description | Useful for most Klebsiella infections. Third-generation cephalosporin with gram-negative activity. Arrests bacterial cell wall synthesis, which, in turn, inhibits bacterial growth. |
| Adult Dose | Moderate infections: 1-2 g IV/IM q6-8h Severe infections: 1-2 g IV/IM q4h |
| Pediatric Dose | Infants and children: 50-180 mg/kg/d IV/IM divided q4-6h >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Probenecid may increase levels; coadministration with furosemide and aminoglycosides may increase nephrotoxicity |
| Pregnancy | B - Usually safe but benefits must outweigh the risks.
|
| Precautions | Excreted in urine; adjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfection and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy; associated with severe colitis |
| Drug Name | Ceftriaxone (Rocephin) |
| Description | Effective for K pneumoniae meningitis and other Klebsiella infections. Third-generation cephalosporin with broad-spectrum, gram-negative activity and higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins. |
| Adult Dose | Meningitis: 2 g IV/IM q12h Other infections: 1-2 g IV/IM q24h |
| Pediatric Dose | Neonates: 25-50 mg/kg/d IV/IM; not to exceed 125 mg/d Infants and children: 50-75 mg/kg/d IV/IM divided q12h; not to exceed 2 g/d |
| Contraindications | Documented hypersensitivity |
| Interactions | Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity |
| Pregnancy | B - Usually safe but benefits must outweigh the risks.
|
| Precautions | Superinfection and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy; caution in breastfeeding
|
| Drug Name | Gentamicin (Garamycin, Jenamicin, Gentafair) |
| Description | Aminoglycoside antibiotic for gram-negative coverage. Bactericidal drug that may be used synergistically with third-generation cephalosporins. Works by binding the bacterial 30S ribosomal subunit, thereby inhibiting protein synthesis. Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be given IV/IM. Monitoring may be required because of the potential to cause cochlear, vestibular, and tubular damage. |
| Adult Dose | Conventional dosing is 3-5 mg/kg/d IV/IM divided q8h in patients with normal renal function; peak serum levels (PSLs) should be drawn 1 h after start of infusion of third dose; in critically ill patients, drawing PSLs after first dose is reasonable because volume of distribution and renal function may change rapidly; ideal body weight is used for dose calculation in patients who are overweight Alternatively, a dose of 5-7 mg/kg IV may be given qd; once-daily dosing renders peak level measurements unnecessary because these are expected to be high; in such patients, monitoring is accomplished with a nomogram based on a 1-compartment pharmacokinetic model; drug levels are obtained 6-14 h after infusion; the nomogram is then used to adjust the dosing interval appropriately; this model is designed for use with 7-mg/kg doses; modifications to the nomogram using 5 mg/kg for gentamicin and tobramycin allow reduction of the dosing interval to 12 h for individuals who clear aminoglycosides rapidly; CrCl must be >20 mL/min to use this nomogram In general, measuring drug levels is not necessary in patients on qd dosing of aminoglycosides who have CrCl >60 mL/min and who have received the drug for <5 d; in elderly persons, patients on concurrent nephrotoxic drugs, and those on long-term therapy, measuring levels is recommended |
| Pediatric Dose | Neonates: 2.5 mg/kg IM/IV qd divided q8-24h <5 years: 2.5 mg/kg IV/IM q8h >5 years: 1.5-2.5 mg/kg/dose IV/IM q8h or 6-7.5 mg/kg/d divided q8h; not to exceed 300 mg/d; monitor as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; because aminoglycosides enhance effects of neuromuscular blocking agents, prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly) |
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
| Precautions | Narrow therapeutic index (avoid long-term therapy unless alternate antibiotics are not available); caution in patients with renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in patients with renal impairment |
| Drug Name | Amikacin (Amikin) |
| Description | For gram-negative bacterial coverage of infections resistant to gentamicin and tobramycin. Irreversibly binds to 30S subunit of bacterial ribosomes, blocks recognition step in protein synthesis, and causes growth inhibition. The same principles of drug monitoring for gentamicin apply to amikacin. |
| Adult Dose | 15 mg/kg/d IV/IM divided q8-12h; may be given q24h; not to exceed 1.5 g/d regardless of higher body weight; ideal body weight is used for dosage calculation in patients who are overweight |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Coadministration with other aminoglycosides, penicillins, cephalosporins, and amphotericin B increases nephrotoxicity; enhances effects of neuromuscular blocking agents; causes respiratory depression; irreversible hearing loss may occur with coadministration of loop diuretics |
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
| Precautions | Relatively wide therapeutic index among all aminoglycosides, but caution should be used in dosing (avoid long-term therapy unless alternate antibiotics are not available); caution in patients with renal failure (not on dialysis), hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission |
| Drug Name | Piperacillin/tazobactam (Zosyn) |
| Description | Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication. |
| Adult Dose | 3 g/0.375 g IV q6h |
| Pediatric Dose | <12 years: Not established >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Tetracyclines may decrease effects of piperacillin; high concentrations of piperacillin may physically inactivate aminoglycosides if administered in same IV line; effects are synergistic when administered concurrently with aminoglycosides; probenecid may increase penicillin levels; high-dose parenteral penicillins may result in increased risk of bleeding; caution with nondepolarizing neuromuscular blockers (may potentiate adverse effects) |
| Pregnancy | B - Usually safe but benefits must outweigh the risks.
|
| Precautions | Perform CBC counts before initiation of therapy and at least weekly during therapy; monitor for liver function abnormalities by measuring AST and ALT during therapy; caution in patients diagnosed with hepatic insufficiencies; perform urinalysis, BUN, and creatinine determinations during therapy and adjust dose if values become elevated |
| Drug Name | Imipenem/cilastatin (Primaxin) |
| Description | When given alone, this beta-lactam carbapenem antibiotic is metabolized by renal dehydropeptidase I, resulting in metabolites toxic to the proximal tubule. Cilastatin is an inhibitor of this enzyme, ensuring adequate levels of imipenem. |
| Adult Dose | 250-500 mg IV q6h, up to 1 g q6h IV for most serious infections; not to exceed 4 g/d |
| Pediatric Dose | <12 years: Not established; 15-25 mg/kg/dose IV q6h suggested for > 3 mo Fully susceptible organisms: Not to exceed 2 g/d Infections with moderately susceptible organisms: Not to exceed 4 g/d >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; pediatric patients with CNS infection (seizure risk); do not use diluents containing benzyl alcohol for constitution of administration to pediatric patients <3 mo |
| Interactions | Coadministration with cyclosporine may increase adverse CNS effects of both agents; coadministration with ganciclovir may result in generalized seizures |
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
| Precautions | Adverse CNS experiences such as confusional states and myoclonic activity are encountered, especially when doses are exceeded or in patients with CNS disorders or renal insufficiency; adjust dose in patients with renal insufficiency; avoid use in children <12 y |
| Drug Name | Ciprofloxacin (Cipro) |
| Description | Indicated for a variety of Klebsiella infections. May be used PO or IV. Inhibits bacterial DNA synthesis and, consequently, growth. |
| Adult Dose | 250-500 mg PO bid for 7-14 d 400 mg IV q12h; may be given q8h in severe or complicated infections |
| Pediatric Dose | <18 years: Not recommended >18 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT) |
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
| Precautions | Commonly reported adverse effects include diarrhea, vomiting, abdominal pain or discomfort, headache, and rash; in prolonged therapy, perform periodic evaluations of organ system function (eg, serum chemistries, LFTs, and CBC counts, which are necessary because of reported incidence of renal failure, nephritis, and hepatic necrosis); adjust dose in patients with renal function impairment; superinfection may occur with prolonged or repeated antibiotic therapy |
| Drug Name | Aztreonam (Azactam) |
| Description | Monobactam inhibits cell wall synthesis during bacterial growth. Active against gram-negative bacilli. Bactericidal. |
| Adult Dose | 0.5-2 g IV/IM q8-12h; not to exceed 8 g/d |
| Pediatric Dose | 30 mg/kg IV q6-8h; not to exceed 120 mg/kg/d |
| Contraindications | Documented hypersensitivity |
| Interactions | Tetracyclines may reduce effects |
| Pregnancy | B - Usually safe but benefits must outweigh the risks.
|
| Precautions | Adjust dose in patients with renal insufficiency or hepatic dysfunction |
| Drug Name | Rifampin (Rifadin, Rimactane) |
| Description | Inhibits DNA-dependent bacterial RNA polymerase. Indicated as second-line agent in select klebsiellae infections. |
| Adult Dose | 10 mg/kg/d PO |
| Pediatric Dose | 600 mg PO qd |
| Contraindications | Documented hypersensitivity |
| Interactions | Induces microsomal enzymes, which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoin, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue 1 or both agents if alterations in LFTs occur) |
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
| Precautions | Obtain CBC counts and baseline clinical chemistries prior to and throughout therapy; in patients with liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur |
| Drug Name | Trimethoprim/sulfamethoxazole (Bactrim, Bactrim DS, Septra DS, Cotrim) |
| Description | Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens except Pseudomonas aeruginosa. Indicated as second-line agent for select infections. Not used for routine treatment of pneumonia. |
| Adult Dose | 1 tab PO bid (double-strength tab) |
| Pediatric Dose | Dosage recommendations are based on TMP component <2 years: Not recommended >2 years Mild to moderate infections: 6-10 mg/kg PO qd divided q12h Serious infections: 15-20 mg/kg/d PO divided q12h |
| Contraindications | Documented hypersensitivity; megaloblastic anemia due to folate deficiency |
| Interactions | May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly persons; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine |
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
| Precautions | Discontinue at first appearance of skin rash or sign of adverse reaction; allergic reactions may vary from mild rash and urticaria to severe reactions including Steven-Johnson syndrome, toxic epidermal necrolysis, and exfoliative dermatitis; patients may have generalized skin eruptions, conjunctival and scleral injections, photosensitivity, pruritus, and rash; commonly encountered adverse reactions include nausea, vomiting, and minor allergic skin reactions such as rash and urticaria Obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusion or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in patients with folate deficiency (eg, persons with long-term alcoholism, elderly persons, those receiving anticonvulsant therapy, or those with malabsorption syndrome); hemolysis may occur in individuals with G-6-PD deficiency; patients with AIDS may not tolerate or respond to TMP-SMZ; caution in patients with renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation |
Transfer
- Transfer patients with serious infections to a tertiary care facility.
Deterrence/Prevention
- Follow hospital protocols for infection control to limit the spread of infection and resistant organisms. Restricting certain antibiotic use for specific indications and duration may help prevent the spread of resistant organisms.
- Proper hand washing is crucial to prevent transmission from patient to patient via medical personnel. Contact isolation should be used for patients colonized or infected with highly antibiotic–resistant Klebsiella strains, such as ESBL-producing organisms.
- Single-use devices may minimize transmission from contaminated equipment.
- Contaminated nebulizers are a major source of hospital-acquired infection; this source has been eliminated through the use of disposable devices.
- Use of protective isolation is generally not recommended. Outbreaks of diarrhea associated with Klebsiella infection in neonatal nurseries should necessitate isolation of affected infants.
- Other suggested measures to prevent nosocomial infections include the following:
- Remove medical devices (eg, catheters, tubes) when no longer needed.
- Use nonalkalinizing gastric cytoprotective agents.
- Place intubated patients in a semirecumbent position.
- When possible, consider decreasing the duration and intensity of immunosuppression in patients who are immunocompromised.
Complications
- Lung abscesses can occur days to weeks after Klebsiella infection. A lung abscess in a patient with a non–community-acquired pneumonia strongly suggests K pneumoniae infection.
- Pulmonary gangrene leading to necrosis involves rapid destruction of part of the lung. This is believed to follow vascular compromise. Fortunately, this is rare.
- Other pulmonary complications include cavitation, empyema, bronchopulmonary fistula, and pleural adhesions.
- Superinfections can occur while patients are treated for K pneumoniae infection; likewise, K pneumoniae infection can be a superinfection that develops during inpatient treatment for another type of pneumonia.
- Sepsis can complicate bacteremia and can result in shock and disseminated intravascular coagulopathy.
Prognosis
- K pneumoniae pneumonia has a 50% mortality rate, even with adequate therapy. The prognosis is worse in patients with alcoholism and bacteremia. Preventive strategies and early diagnosis/treatment help to reduce morbidity.
Medical/Legal Pitfalls
- Distinguishing between nosocomial colonization and infection helps limit iatrogenic complications, especially those related to unneeded antibiotics. These include development of resistance, superinfection with resistant organisms, phlebitis, and unnecessary hospital stays.
- Failure to follow recommended isolation procedures is another pitfall. Strict adherence is required to prevent the spread of antimicrobial-resistant nosocomial pathogens.
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Klebsiella Infections excerpt Article Last Updated: Apr 27, 2006
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