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AUTHOR AND EDITOR INFORMATION

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Author: 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

Burke A Cunha is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Editors: Charles S Levy, MD, Associate Professor, Department of Medicine, Section of Infectious Disease, George Washington University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Richard B Brown, MD, FACP, Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine; Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital; Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center

Author and Editor Disclosure

Synonyms and related keywords: Burkholderia infection, Burkholderia cepacia, B cepacia infection, B cepacia colonization, B cepacia complex, Burkholderia cepacia complex, BCC, Burkholderia colonization, Burkholderia cepacia infection, Burkholderia cepacia colonization, nonaeruginosa pseudomonad, cystic fibrosis, Burkholderia pneumonia, Burkholderia bacteriuria, Burkholderia pseudobacteremia, Burkholderia cepacia pneumonia, B cepacia pneumonia

INTRODUCTION

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Background

Burkholderia cepacia is an aerobic gram-negative bacillus found in various aquatic environments. B cepacia is an organism of low virulence and is a frequent colonizer of fluids used in the hospital (eg, irrigation solutions, intravenous fluids). B cepacia rarely causes infection in healthy hosts. Based on phenotypic and genotypic analyses, B cepacia is divided into 9 genomovars that constitute the B cepacia complex (BCC).

Pathophysiology

B cepacia is almost always a colonizing bacterium rather than an infecting bacterium, but it is especially important when isolated from body fluids that are ordinarily sterile. The pathophysiology of B cepacia infection mirrors that of other nonfermentative aerobic bacilli.

Frequency

United States

B cepacia is generally not a pathogen in the ambulatory setting, but it may colonize and/or infect the respiratory tract of patients with cystic fibrosis. B cepacia may also cause catheter-related infections in patients with cancer and in those on hemodialysis. B cepacia nosocomial pneumonia has also been reported, especially in patients who have been treated with fluoroquinolones and ceftazidime antibiotics. Skin and soft-tissue infections, surgical-wound infections, and genitourinary tract infections with B cepacia have also been reported.

International

B cepacia is generally not a pathogen in the ambulatory setting, but it may colonize and/or infect the respiratory tract of patients with cystic fibrosis.

Mortality/Morbidity

  • If an intravenous infusate contains high numbers of B cepacia, direct injection into the bloodstream may induce the signs and symptoms associated with gram-negative bacteremia.
  • Gram-negative bacteremia may occur if urologic irrigation fluids that contain B cepacia are used during an invasive urologic procedure.


CLINICAL

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History

  • A history of the use of irrigant solutions that may have contained B cepacia is epidemiologically important.

Physical

  • Physical examination is referable to the organ system involved.

Causes

  • B cepacia is a nonfermentative, aerobic, gram-negative bacillus formerly classified as Pseudomonas. Unlike Pseudomonas aeruginosa, B cepacia is an organism of low virulence with a limited ability to cause infection in humans.
  • B cepacia survives and multiplies in aqueous hospital environments, where it may persist for long periods.
  • Sources of B cepacia colonization include the following:
    • Personnel - Hands, antiseptic soaps, hand lotion1
    • Respiratory equipment and/or fluids - Respirator tubing condensate, ultrasonic nebulizers,2 inhalation medications
    • Intravenous lines and/or fluids - Intravenous solutions, central venous catheters
    • Pressure-monitoring devices - Pressure transducer fluids
    • Urine and/or fluids - Indwelling Foley catheters, urometers, irrigation solutions


DIFFERENTIALS

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Other Problems to be Considered

B cepacia recovered from blood cultures may represent infection associated with contaminated intravenous fluids (infusate-related).

Regard the recovery of B cepacia from the respiratory secretions or urine of catheterized patients as colonization until proven otherwise.

B cepacia is a common cause of catheter-associated bacteriuria in hospitalized patients. B cepacia commonly colonizes the urine and is potentially pathogenic only in individuals with impaired host defenses (eg, patients on steroids or those with diabetes, systemic lupus erythematosus [SLE], multiple myeloma, or cirrhosis).

B cepacia is an extremely rare cause of nosocomial pneumonia. In ventilated patients with presumed nosocomial pneumonia who have fever, pulmonary infiltrates, and leukocytosis, B cepacia cultured from respiratory secretions generally represents colonization rather than infection.

Nosocomial infections caused by B cepacia include the following:

  • Catheter-associated bacteriuria - Indwelling urinary catheters
  • Intravenous line infections - Central intravenous catheters
  • Urosepsis - Urinary tract instrumentation
  • Primary bacteremia - Arterial monitoring devices
  • Pseudobacteremia - Contamination of blood during collection and/or processing of blood cultures


WORKUP

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Lab Studies

  • Culture B cepacia from body fluids.
  • Although B cepacia–positive cultures from nonsterile sites (eg, respiratory secretions, urine in the setting of Foley catheters) nearly always represent colonization, presence in sterile body fluids such as blood mandates consultation with an infectious disease specialist.


TREATMENT

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Medical Care

  • Patient-to-patient spread of B cepacia may be minimized and/or prevented with effective infection-control measures.
  • Use Foley catheters only as long as necessary. If possible, avoid their use in compromised hosts predisposed to urinary tract infections (eg, patients with diabetes, SLE, multiple myeloma).
  • Preventing B cepacia colonization of respiratory secretions in intubated patients who are in ICUs and on broad-spectrum antibiotics is difficult.

Consultations

  • Consultation with an infectious disease specialist helps to differentiate B cepacia colonization from infection.


MEDICATION

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Because B cepacia is almost always a colonizer, antimicrobial treatment is unnecessary and may be harmful unless infection is proven.

B cepacia, as a nonaeruginosa pseudomonad, is usually resistant to aminoglycosides, antipseudomonal penicillins, and antipseudomonal third-generation cephalosporins.

B cepacia is often susceptible to trimethoprim plus sulfamethoxazole (TMP-SMX), cefepime, meropenem, minocycline, and tigecycline and has varying susceptibility to fluoroquinolones.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug NameTrimethoprim and sulfamethoxazole (Bactrim DS, Septra DS)
DescriptionInhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity includes common urinary tract pathogens, except P aeruginosa.
Adult Dose160 mg TMP/800 mg SMX PO/IV q12h for 10-14 d
Pediatric Dose<2 months: Do not administer
>2 months: 15-20 mg TMP/kg/d PO tid/qid for 14 d
ContraindicationsDocumented hypersensitivity; megaloblastic anemia due to folate deficiency
InteractionsMay 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 individuals; 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
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsDiscontinue at first appearance of skin rash or sign of adverse reaction; obtain CBCs frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, administer 5-15 mg/d leucovorin); caution in folate deficiency (eg, individuals with chronic alcoholism, elderly individuals, those receiving anticonvulsant therapy, 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 renal or hepatic impairment (perform urinalyses and renal function tests during therapy); administer fluids to prevent crystalluria and stone formation

Drug NameCefepime (Maxipime)
DescriptionFourth-generation cephalosporin with good gram-negative coverage; similar to ceftazidime, but with better gram-positive coverage.
Adult Dose2 g IV q12h
Pediatric Dose50 mg/kg IV q8h
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid at high doses may increase effects of cefepime; aminoglycosides increase the nephrotoxic potential of cefepime
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsAdjust dose in patients with severe renal insufficiency (high doses may cause CNS toxicity); prolonged use may predispose patients to superinfection

Drug NameTigecycline (Tygacil)
DescriptionA glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. Inhibits bacterial protein translation by binding to 30S ribosomal subunit and blocks entry of amino-acyl tRNA molecules in ribosome A site. Indicated for complicated skin and skin-structure infections caused by E coli, E faecalis (vancomycin-susceptible isolates only), S aureus (methicillin-susceptible and -resistant isolates), S agalactiae, S anginosus group (includes S anginosus, S intermedius, S constellatus), S pyogenes, and B fragilis.
Adult DoseInfuse each dose over 30-60 min
100 mg IV once, then 50 mg IV q12h
Severe hepatic impairment (ie, Child Pugh class C): 100 mg IV once, then 25 mg IV q12h
Pediatric Dose<18 years: Not established
>18 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsCoadministration decreases warfarin clearance and increases warfarin Cmax and AUC (monitor aPTT and INR); coadministration of antibiotics with oral contraceptives may decrease contraceptive effect
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsCaution in severe hepatic impairment (reduce dose); may adversely effect tooth development; may permit clostridia overgrowth, resulting in antibiotic-associated colitis; may have adverse effects similar to tetracyclines (eg, photosensitivity, pseudotumor cerebri, pancreatitis, antianabolic action)

Drug NameMeropenem (Merrem IV)
DescriptionSemisynthetic carbapenem antibiotic that inhibits bacterial cell wall synthesis. Effective against most gram-positive and gram-negative bacteria.
Has slightly increased activity against gram-negative bacteria and slightly decreased activity against staphylococci and streptococci compared to imipenem.
Adult Dose1 g IV q8h
Pediatric Dose<10 years: Not established
>10 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid may inhibit renal excretion of meropenem, increasing meropenem levels
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsPseudomembranous colitis and thrombocytopenia may occur, requiring immediate discontinuation of medication; adjust dose in patients with renal impairment

Drug NameCefixime (Suprax)
DescriptionThird-generation oral cephalosporin with broad activity against gram-negative bacteria. By binding to one or more of the penicillin-binding proteins, it arrests bacterial cell wall synthesis and inhibits bacterial growth.
Adult Dose400 mg/d PO qd or 200 mg q12h
Pediatric Dose<50 kg or <12 years: 8 mg/kg/d suspension PO qd or 4 mg/kg bid
>50 kg or >12 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsCoadministration of aminoglycosides increase nephrotoxicity; probenecid may increase effects of cefixime
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsAdjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections, and promotion of non-susceptible organisms may occur with prolonged use or repeated therapy

Drug NameMinocycline (Dynacin, Minocin)
DescriptionTreats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma. Was found to be effective in some non-tuberculotic mycobacterial infections.
Adult Dose100 mg PO bid for 5-7 d
Pediatric Dose<8 years: Not recommended
>8 years: 4 mg/kg PO initially, followed with 2 mg/kg q12h
ContraindicationsDocumented hypersensitivity; severe hepatic dysfunction
InteractionsBioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsPhotosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one-half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines; hepatitis or lupuslike syndromes may occur


FOLLOW-UP

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Deterrence/Prevention

  • Effective infection-control measures can minimize or limit the spread of B cepacia and other organisms in the ICU.
  • Recovered B cepacia should be considered a nonpathogen unless proven otherwise.
  • If B cepacia is recovered from several patients in the same area, sections of an ICU or ward can become the focus for further B cepacia colonizations within the hospital setting.
  • Appropriate isolation procedures rather than antimicrobial therapy should be used to control the spread of B cepacia colonization among patients.

Complications

  • Because B cepacia is normally a colonizer, no complications are expected.


MISCELLANEOUS

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Medical/Legal Pitfalls

  • B cepacia bacteriuria ordinarily should not be treated. In a patient with an indwelling Foley catheter, B cepacia may be accompanied by pyuria, which represents colonization rather than infection unless recent antecedent urologic instrumentation has occurred.
  • The most common clinical error with B cepacia involves the treatment of patients on respirators in ICUs in whom B cepacia is recovered from respiratory secretions.
  • Because B cepacia does not generally cause pneumonia, isolation of B cepacia from a respiratory secretion does not warrant treatment unless nosocomial pneumonia is clearly evident.
  • The needless and inappropriate treatment of B cepacia colonization with antibiotics (eg, TMP-SMX) may predispose patients to adverse drug effects (eg, drug rash and/or fever due to the sulfisoxazole component of TMP-SMX).


REFERENCES

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Burkholderia excerpt

Article Last Updated: Oct 14, 2008