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Gram Positive Bacteria
Enterobacteriaceae (Gram Negative Bacilli)
1] Citrobacter koseri
2] Citrobacter freundii
1] Enterobacter cloacae,
2] Enterobacter aerogenes)
1] Klebsiella ozaenae
2] Klebsiella pneumoniae
3] Klebsiella rhinoscleromatis
1] (Morganella morganii)
1] Proteus mirabilis
2] Proteus vulgaris
2] Providencia stuartii
1] Salmonella enteritidis
2] Salmonella typhi
1] Shigella dysenteriae (serogroup A)
2] Shigella flexneri
3] Shigella boydii
4] Shigella sonnei
Ubiquitous non-motile, Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule.
Frequent human pathogens, Klebsiella organisms can lead to a wide range of disease states, notably pneumonia, urinary tract infections, septicemia, and soft tissue infections.
Klebsiella species have also been implicated in the pathogenesis of ankylosing spondylitis and other spondyloarthropathies.
Klebsiella pneumoniae is the most common cause of nosocomial respiratory tract and premature intensive care infections, and the second most frequent cause of Gram-negative bacteraemia and urinary tract infections. Drug resistant isolates remain an important hospital-acquired bacterial pathogen, add significantly to hospital stays, and are especially problematic in high impact medical areas such as intensive care units.
Gram-negative, non-motile, encapsulated, lactose-fermenting, facultative anaerobic, rod-shaped bacterium. It is closely related to K. oxytoca from which it is distinguished by being indole-negative and by its ability to grow on both melezitose and 3-hydroxybutyrate.
Found in the normal flora of the mouth, skin, and intestines. Generally, Klebsiella infections are seen mostly in people with a weakened immune system.
Can cause destructive changes to human lungs if aspirated (access is typically gained after a person aspirates colonizing oropharyngeal microbes into the lower respiratory tract).
Clinically, it is the most significant member of the Klebsiella genus of Enterobacteriaceae.
New antibiotic resistant strains of K. pneumoniae are appearing, and it is increasingly found as a nosocomial infection.
Seven species of the Klebsiella genus, with demonstrated similarities in DNA homology are known:
(1) Klebsiella pneumoniae,
(2) Klebsiella ozaenae,
(3) Klebsiella terrigena,
(4) Klebsiella rhinoscleromatis,
(5) Klebsiella oxytoca,
(6) Klebsiella planticola, and
(7) Klebsiella ornithinolytica.
K oxytoca and K rhinoscleromatis have also been demonstrated in human clinical specimens.
In recent years, klebsiellae have become important pathogens in nosocomial infections.
The most common infection caused by Klebsiella bacteria outside the hospital is pneumonia, typically in the form of bronchopneumonia and also bronchitis. These patients have an increased tendency to develop lung abscess, cavitation, empyema, and ural adhesions. It has a high death rate of about 50% even with antimicrobial therapy. The mortality rate can be nearly 100% for persons with alcoholism and bacteremia.
In addition to pneumonia, Klebsiella can also cause infections in the urinary tract, lower biliary tract, and surgical wound sites. The range of clinical diseases includes pneumonia, thrombophlebitis, urinary tract infection (UTI) (Klebsiella ranks second to E. coli for urinary tract infections in older persons), cholecystitis, diarrhea, upper respiratory tract infection, wound infection, osteomyelitis, meningitis, and bacteremia and septicemia.
One of many carbapenem-resistant Enterobacteriaceae (CRE) is Carbapenem-Resistant Klebsiella pneumoniae (CRKP). Over the past 10 years, a progressive increase in CRKP has been seen worldwide. CRKP is resistant to almost all available antimicrobial agents, and infections with CRKP have caused high rates of morbidity and mortality, in particular among persons with prolonged hospitalization and those critically ill and exposed to invasive devices (e.g., ventilators or central venous catheters).
There are a number of mechanisms of Carbapenem Resistance in Enterobacteriaceae.
(1) Hyperproduction of ampC beta-lactamase with an outer membrane porin mutation
(2) CTX-M extended-spectrum beta-lactamase with a porin mutation or drug efflux, and
(3) Carbapenemase production. When Klebsiella pneumoniae bacteria produce the carbapenemase enzyme they are known as KPC-producing organisms or carbapenem-resistant Klebsiella pneumoniae (CRKP).
Klebsiella organisms are often resistant to multiple antibiotics. Current evidence implicates a plasmid as the source of the resistant genes. Klebsiella with the ability to produce
are resistant to many classes of antibiotics.
: The choice of an agent should be based on local antimicrobial sensitivities, site of infection, cost, and comorbid conditions. Generally, the most common agents/regimens are listed first. Listed dosages may need to be adjusted for renal dysfunction.
: Growing worldwide resistance to a broad array of antibiotics. Therapy should be guided by susceptibility testing. Extended spectrum beta-lactamase (
) and carbapenemase production is a growing problem.
1-2 grams IV q24h (range: 1-2 grams q12-24h)
400mg IV q12h (Severe/complicated: 400mg IV q8h)
(Zosyn ®) 3.375 grams IV q6h
750 mg IV/PO once daily
Extended spectrum beta-lactamase (ESBL) producing strains
500mg IV every 6 hours [Range: 250-1000 mg q6-8h]
Meropenem 0.5 - 1 gram IV q8h
Carbapenemase producing strains - Carbapenem-resistant enterobacteriaceae (CRE)
Colistimethate (colistin base): 2.5 - 5mg/kg/day in 2-4 divided doses. Max 5 mg/kg/day
[ Meropenem 1 gram IV q8h OR
500mg IV every 6 hours [Range: 250-1000 mg q6-8h]
Infectious Disease Section References
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Arnold FW, LaJoie AS, Brock GN, Peyrani P, Rello J, Menéndez R, et al. Improving outcomes in elderly patients with community-acquired pneumonia by adhering to national guidelines: Community-Acquired Pneumonia Organization International cohort study results. Arch Intern Med. Sep 14 2009;169(16):1515-24.
Baden LR, Eisenstein BI.Impact of Antibiotic Resistance on the Treatment of Gram-negative Sepsis. Curr Infect Dis Rep. 2000 Oct;2(5):409-416.
Bartlett JG et al. Community-acquired pneumonia in adults: guidelines for management. Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 1998;26:811-38.
Bartlett JG: Empirical therapy of community-acquired pneumonia: macrolides are not ideal choices. Semin Respir Infect 1997 Dec; 12(4): 329-33
Bartlett JG.1998 Pocket Book of Infectious Disease Therapy., Ninth Edition. Baltimore,MD: Williams&Wikins,1998.
Bernstein JM: Treatment of community-acquired pneumonia--IDSA guidelines. Infectious Diseases Society of America. Chest 1999 Mar; 115(3 Suppl): 9S-13S
Brown SM, Jones BE, Jephson AR, Dean NC. Validation of the Infectious Disease Society of America/American Thoracic Society 2007 guidelines for severe community-acquired pneumonia. Crit Care Med. Dec 2009;37(12):3010-6.
CDC. Update to CDC's sexually transmitted diseases treatment guidelines, 2006. fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep. Apr 13 2007;56(14):332-6.
CDC. Centers for Disease Control and Prevention. 2010 STD Treatment Guidelines.
Cunha BA. Antibiotic Essentials 8th.ed. Jones & Bartlett Learning, 2009.
Ewig S et al. Pneumonia acquired in the community through drug-resistant Streptococcus pneumoniae. Am J Respir Crit Care Med. 1999;159:1835-42.
Fang WF, Yang KY, Wu CL, Yu CJ, Chen CW, Tu CY, et al. Application and comparison of scoring indices to predict outcomes in patients with healthcare-associated pneumonia. Crit Care. Jan 19 2011;15(1):R32.
File TM Jr. Community-acquired pneumonia: recent guidelines for therapy. J Respir Dis. 1999;20:534-41.
Gilbert DN, Moellering Jr RC, Eliopoulos GM, et al ed. The Sanford Guide to Antimicrobial Therapy, 40th ed. Sperryville, VA: Antimicrobial Therapy; 2010.
Gold HS, Moellering RC. Antimicrobial-drug resistance. N Engl J Med. 1996;335:1445-1453.
Gonzales R, Sande M: What will it take to stop physicians from prescribing antibiotics in acute bronchitis? Lancet 1995 Mar 18; 345(8951): 665-6
Hooton TM, Stamm WE. Diagnosis and treatment of uncomplicated urinary tract infection. Infect Dis Clin North Am 1997;11:551-581.
Lacy CF, Armstrong LL, Goldman MP, Lance LL. Drug Information Handbook. 20th ed. Hudson, OH: Lexi-Comp, Inc; 2011.
Lipsky BA, Berendt AR.Principles and practice of antibiotic therapy of diabetic foot infections. Diabetes Metab Res Rev. 2000 Sep-Oct;16 Suppl 1:S42-6.
Mandell LA , Wunderink RG , Anzueto A , et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults . Clin Infect Dis . 2007;44(suppl 2):S27–S72.
Mufson MA.Pneumococcal Pneumonia. Curr Infect Dis Rep. 1999 Apr;1(1):57-64.
Nabel EG, Federman DD. Infectious Diseases: The Clinician's Guide to Diagnosis, Treatment, and Prevention. Jackson, WY: Teton Data Systems, 2010.
Phua J, See KC, Chan YH, Widjaja LS, Aung NW, Ngerng WJ, et al. Validation and clinical implications of the IDSA/ATS minor criteria for severe community-acquired pneumonia. Thorax. Jul 2009;64(7):598-603.
Pirracchio R, Mateo J, Raskine L, Rigon MR, Lukaszewicz AC, Mebazaa A, et al. Can bacteriological upper airway samples obtained at intensive care unit admission guide empiric antibiotherapy for ventilator-associated pneumonia?. Crit Care Med. Sep 2009;37(9):2559-63.
Reese RE, Betts RF: A Practical Approach to Infectious Diseases. 4th ed. Boston: Little, Brown, and Company; 1996: 251
Runyon B. Ascites and spontaneous bacterial peritonitis. In: Feldman M, Friedman LS, Sleisenger MH, eds. Sleisenger & Fordtran's Gastrointestinal and Liver Disease. Vol 2. 8th ed. Philadelphia, Pa: Saunders; 2006:1935-64.
Rybak MJ, Lomaestro BM, Rotschafer JC, et al: Therapeutic monitoring of vancomycin in adults: summary of consensus recommendations from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Pharmacotherapy 2009; 29:1275-1279.
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Braz J Infect Dis. 1998 Jun;2(3):109-117.
Stamm WE, Hooton TM. Management of urinary tract infections in adults. N Engl J Med 1993;329:1328-1334.
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van der Poll T, Opal SM. Pathogenesis, treatment, and prevention of pneumococcal pneumonia. Lancet. Oct 31 2009;374(9700):1543-56.
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