Unusual Case of Infant Septicemia Involving Burkholderia cepacia

Lisa Cleveland

Department of Clinical Laboratory Sciences

School of Health Related Professions

University of Mississippi Medical Center

Jackson, MS 39216

lcleveland@shrp.umsmed.edu
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Abstract

The following is case study involving Burkholderia (Pseudomonas) cepacia as both rare and

unusual causative agent of infant septicemia. This organism is nonfermentative gram negative

rod that is mainly associated with respiratory infections of elderly and immunocompromised

patients with serious pulmonary problems. The only cases in which B. cepacia has been reported

as a cause of infection among children involves cystic fibrosis (CF) patients and nosocomial

neonatal outbreaks. However, the only health complications this child has had are reoccurring

infections of urinary tract and otitis media. The patient was first seen at a walk-in clinic with

fever, lethargy, and suspected UTI for which she was treated with antibiotics. Unfortunately, the

mother failed to bring the infant back for follow-up. About one month later, the child was taken

to the ED and hospitalized. During first days of hospitalization, the infant had negative urine and

blood cultures. However, the child’s white cell count was gradually increasing. Thus, on the

fourth day the infant had a fever spike of 104°F in which blood cultures were collected for three

consecutive days and resulted in isolation of B. cepaica.

Among children, urinary and respiratory tracts are two focal routes of infection that have a high

incidence of septicemia. Septicemia is serious bacterial infection of the bloodstream that has a

high mortality rate, especially when involving gram negative bacteria that are capable of

producing endotoxins. Therefore, early detection and treatment allows for a better prognosis.

This is accomplished by the use of blood cultures that allow for isolation, identification, and

antibiotic susceptibility testing of bacteria.

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Unusual Case of Infant Septicemia Involving Burkholderia cepacia

Case Presentation

At a walk-in clinic an eight month old girl presented to a pediatrician with a fever of 103.9°F,

urinary tract, and otitis media infections. The child had been running a mild fever and vomiting

two to three days earlier. Due to such a high fever a urine specimen for culture was taken by

catherization and was sent to an out of state reference lab. However, no blood or ear cultures

were collected. According to the reference lab report, the urine culture contained a mixture of E.

coli and Pseudomonas aeroginosa. The medical summary stated that the child had a history of

six or more previous otitis media infections. Also, both parents smoke, so the child is constantly

exposed to second-hand cigarette smoke. Thus, she was given Rocephin (Ceftriaxone) followed

by Amoxillin (Ampicillin). The mother was told to return the following day, but she did not.

Unfortunately, the family did not return until about one month later when the infant was

brought to the emergency department (ED) with a mild fever, vomiting, lethargy, and anorexia.

Based on the past medical summary, consisting of a history of urinary tract infections (UTI) and

abnormal renal ultrasounds related to the presence of kidney stones, she was initially admitted

with a diagnosis of urinary tract infection. While in the ED blood cultures were drawn, which

were negative. When admitted the patient was started on I.V. Claforan (Cefotaxime). Also,

urine specimen was collected for culture, which was negative. However, it was obtained after

administration of antimicrobial therapy was started.

After being hospitalized for three days, the patient was going to be discharged based on the

fact that she had regained her appetite, had both negative urine and blood cultures, and only had

a mild fever, but no spikes. However, about 4:55 p.m. the child had a fever spike of 104°F on

third day. Thus, over a period of three days (days 3-5) blood cultures were collected, which were
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positive on days 4 and 5 for a nonfermentative gram negative rod identified using manual API

System (BioMerieux Hazelwood, Mo.) as Burkholderia (Pseudomonas) cepacia. Also, due to

the extended use of broad-spectrum antimicrobics, the child was positive for Clostridium difficle

toxin. Table 1 shows the patient’s white blood cell count (WBC) in correlation with positive

blood cultures. The infant’s immune system responded to the septicemia by dramatically

increasing production of leukocytes and causing fever spikes that were seen between days 4-5.

TABLE 1:

DAY WBC/µ L** Blood Culture Organism

3 11,300 normal N/A N/A
4 12.500 normal Positive B. cepacia
5 morning 18,100 high Positive B. cepacia
5 evening 20,400 high N/A* N/A*
*only one blood culture for day 5 **Normal Range 6,000-17,000/µ L

On day 6, the child was transferred to a large tertiary care medical center for pediatric care.

The patient was placed on I.V. Rocephin and Gentamicin (Garamycin), until sensitivity report

was received. Based on results of the antimicrobic sensitivity testing (resistance to Rocephin),

treatment was changed to Fortax (Ceftazidime) and Batrim (Sulfametrioxazole/Trimethoprim).

When B. cepacia is identified in children, the first disease association that comes to mind is

cystic fibrosis (CF). Thus, sweat chloride tests were performed on both arms, which were

negative. Both urine and blood cultures were collected, which were negative. Also, culture of

the patient’s organism was sent to medical center’s pediatric infectious diseases department.

Using the Vitek System (BioMerieux Hazelwood, Mo.), the identification of the isolate was

confirmed as B. cepacia.

Burkholderia (Pseudomonas) cepacia

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Burkholderia (Pseudomonas) cepacia is a nonfermentative gram negative rod that is an

opportunistic pathogen causing serious pulmonary infections of CF patients and other

immunocompromised individuals. However, the bacterium has been recovered as an agent

causing infections of urinary tract, bloodstream, and nosocomial outbreaks (1). Basically, B.

cepacia is found in moist soil environments, thus it has become very metabolically adaptable and

hardy. For example, this organism can utilize naturally occurring antibiotics in soils as a nutrient

source. In hospitals, it has been known to cause many outbreaks due to the ability to survive and

grow in cleaning solutions, water supplies, and colonize medical equipment. Over time, due to

genetic factors and mutations B. cepacia has become multiresistant, thus, in many instances,

requiring a combination of antibiotics for successful treatment (2). Isolation and identification of

B. cepacia can be difficult due to the fact that it is slow growing and sometimes the biochemical

reactions are variable. There is a selective medium for B. cepacia; however, it is unnecessary for

a hospital lab unless the hospital has a high incidence of CF or other pulmonary diseases.

Gram negative septicemia

Septicemia is when bacteria are introduced into the bloodstream and multiply at a rate

greater than the body can defend, thus causing infection. Some of the basic symptoms and signs

include fever, rash, lethargy, irritability, and chills. Gram negative bacteria, especially E.coli

and Klebsiella species, are the major causes of septicemia in children (3). There are some key

structural components of gram negative bacteria that make early detection and treatment

extremely critical in preventing mortality and morbidity.

The cell wall of gram negative bacteria is complex in both structure and function. The cell

wall consists of two layers (outer and inner membranes) divided by a periplasmic space (4a).

First, the inner membrane is composed of a very thin peptidoglycan layer. The outer membrane

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consists of phospholipids, proteins, lipoplysaccharides (LPS). One role of this membrane is to

function as a permeability barrier that regulates the movement of large molecules and

hydrophobic compounds. However, the LPS is the major structural component involved in

enhancing both pathogencity and virulence of gram negative bacteria. LPS consists of three

regions that include lipid A (endotoxins), core, and antigen O-specific polysaccharide (somatic

antigen) (4b, 5). Lipid A is thought to be responsible for most of the properties of endotoxins,

which is the toxic portion of LPS that is released mainly during cell death. In severe gram

negative infections, endotoxins cause many harmful complications that result in high mortality

rates. For example, when LPS is released from the outer membrane, it binds to a LPS-binding

protein that is present in the bloodstream, resulting in the formation of a toxic complex that

interacts with immune system components such as monocytes and macrophages. This

interaction causes production of cytokines and activation of both complement and coagulation

cascades. This interaction can lead to inflammation, disseminated intravascular coagulation

(DIC), massive hemorrhage, and septic shock (6).

Routes of septicemia infections

For infants, the most common routes of acquiring septicemia are through urinary and

respiratory tract infections. First, one of the most common bacterial infections among humans

involves the urinary tract. People of all ages are at risk, however elderly, infants, and

immunocompromised are at greater risk. Most urinary infections are easy to diagnose and treat.

UTIs involving infants can be difficult to detect due to the variation in clinical presentation,

communication, and difficulties with specimen collection. Some of the common signs and

symptoms include vomiting, diarrhea, lack of appetites, and irritability (7). UTIs that go

untreated in children can become very serious due to the potential of bacteria disseminating into

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the bloodstream. The kidneys main functions are to filter the blood and remove waste from the

body in the form of urine. Normally, urine goes from the kidney to the bladder, and then is

excreted out of the body. However, there are some abnormalities that cause blockage or reflux

of this process such as renal stones, which greatly increase the risk of developing and having

reoccurring UTIs. Therefore, when the flow of urine is decreased or reflux occurs bacteria are

given an opportunity to colonize and multiply at a rate greater than the body can handle. Thus, if

the UTI goes untreated, a condition known as urosepsis can occur. Basically, urosepsis starts out

as urinary infection that goes untreated or mistreated, thus bacteria are able to invade the intact

mucosa and disseminate into the bloodstream resulting in septicemia (4c). Another common

route for children acquiring septicemia is from respiratory tract infections especially in cases of

reoccurring bacterial pneumonia and otitis media. However, the most common organism

responsible for these infections include: Streptococcus pneumoniae, Neisseria meningitidis,

Haemophilus influenzae, and Pseudomonas aeroginosa.

Conclusion

When bacterial infections are suspected among children, many health care providers

prescribe antibiotics and avoid culturing the focal site of infection; therefore, they lack the proper

identification and susceptibility pattern of an organism. This prompt treatment is great when a

bacterium is susceptible. However, when the organism is resistant or tolerant, this type of

treatment can cause invasive infections and lead to multiresistant bacteria. In ED and walk-in

clinics, when diagnosing children with bacterial infections it is important to culture for the

infecting agent and include blood cultures, especially when suspect infectious agents have

disseminated into bloodstream. This is common in children due to not knowing how long they

have had an infection. The use of blood cultures does not guarantee an organism will be detected

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due to some factors that may lead to false negative results such as antibiotics circulating in the

bloodstream or too small quantity of blood. When viral infections are suspected, blood cultures

are not necessary. The criteria for ordering blood cultures differs for each healthcare facility,

however some basic guidelines need to be established such as the following (8, 9). One,

determine the focal sites (routes) of infection in children with high incidence of becoming

invasive such as gastroenteritis, urinary and respiratory tract infections. Two, determine most

common ages in which septicemia/bacteremia in children occurs such as most common among

neonates and infants less than two years of age (3). Third, determine factors in a child’s medical

history that increases the risk for disseminated infections such as genetic diseases, cancers,

structural abnormalities, and reoccurring infections. Fourth, identify combination of specific

signs and symptoms indicative of an invasive infection such as fever >101°F, lethargy, rash,

vomiting, and increase in white cell count (WCC) focusing in particular on increased

neutrophils.

In this case based on the criteria above, blood cultures were required when the child

presented to walk-in clinic and ED with a fever, lethargy, and suspected UTI. Although, B.

cepacia was never isolated from the urine, the focal site of infection leading to septicemia is

most likely urinary tract. There are certain factors that may have affected the growth and

recovery of B. cepacia from the urine cultures such as inhibition by antibiotics or may have been

overtaken/hidden by the growth of E.coli and P. aeroginosa on the culture plates.

Fortunately, the organism was recovered and identified allowing the child to overcome this

severe infection after several days of treatment with a combination of antibiotics. Presently, the

follow-up reports conclude the child is healthy and all tests are normal.

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Work Cited
1. Mangram, Alicia and Jarvis R. William. “Nosocomial Burkholderia cepacia Outbreaks and
Pseudo-Outbreaks.” Infection Control and Hospital Epidemiology Nov 1996; Vol 17(11):1.
14 Sept. 2002.
2. Holmes, Govan, and Richard Goldstein. “Agriculture use of Burkholderia (Pseudomonas)
cepacia: A Threat to Human Health?” 1-2.. 14 Sept. 2002.
3. Levy, Itzhak; Leibovici, Lenard, Drucker, Moshie; Samra, Zmira, Konisberger, Hana. “A
prospective study of Gram-negative bacteremia in children.” The Pediatric Infectious
Disease Journal. Feb 1996; Vol. 15: 117-122. Nov. 2002.
4a. Koneman, Allen and Janda Schrechenberger. Color Atlas and Textbook of Diagnostic
Microbiology 5th edition. 12-14.
4b. ibid. 29-30.
4c. ibid. 137.
5. White, David. The Physiology and Biochemistry of Prokaryotes. 2nd edition. 2000. 17-18.
6. Ryan, J. Kenneth. Sherris Medical Microbiology: An Introduction to Infectious Diseases. 3rd
edition. 1994. 157.
7. Bartkowski, Donald P. “Recognizing UTIs in infants and children.” Postgraduate Medicine.
Jan 2001: Vol. 109(1): 171. 14 Dec. 2002.
8. Teele, David., Pelton, Stephen, Grant, Myles. “Bacteremia in febrile children under 2 years
of age: Results of cultures of blood of 600 consecutive febrile children seen in a “walk-in”
clinic. The Journal of Pediatrics 1975. 227
9. Nimri, L.F, Rawashdeh,M., Meqdam, M.M. “ Bacteremia in Children: Etiologic Agents,
Focal Sites, and Risk Factors.” Journal of Tropical Pediatrics. Dec 2001, 47: 356.

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