70 BruCELLOSiS
21
BruCELLOSiS 71 persist for months or years after initial infection.
Increased concentrations of IgG agglutinins are found in acute infection, chronic infection, and relapse. When interpreting serum agglu- tination test results, the possibility of cross- reactions of Brucella antibodies with antibodies against other gram-negative bacteria, such as Yersinia enterocolitica serotype 09, Francisella tularensis, and Vibrio cholerae, should be con- sidered. Enzyme immunoassay is a sensitive method for determining IgG, IgA, and IgM anti-Brucella antibody titers. Until better stan- dardization is established, enzyme immuno- assay should only be used for suspected cases with negative serum agglutination test results or for evaluation of patients with suspected chronic brucellosis, reinfection, or complicated cases. Polymerase chain reaction tests have been developed but are not available in most clinical laboratories.
Treatment
Prolonged antimicrobial therapy is imperative for achieving a cure. Relapses generally are not associated with development of Brucella
resistance but rather with premature discon- tinuation of therapy. Because monotherapy is associated with a high rate of relapse, com- bination therapy is recommended as standard treat ment. Most combination regimens include oral doxycycline or trimethoprim- sulfamethoxazole plus rifampin.
For treatment of serious infections or compli- cations, including endocarditis, meningitis, spondylitis, and osteomyelitis, a 3-drug regi- men should be used with gentamicin included for the first 7 to 14 days, in addition to tetra- cycline (or trimethoprim-sulfamethoxazole, if tetracyclines are not used) and rifampin for a minimum of 6 weeks. For life-threatening complications of brucellosis, such as menin- gitis or endocarditis, the duration of therapy is often extended for 4 to 6 months. Surgical intervention should be considered in patients with complications, such as deep tissue abscesses, endocarditis, mycotic aneurysm, and foreign body infections.
The benefit of corticosteroids for people with neurobrucellosis is unproven.
Image 21.1
A calcified Brucella granuloma in the spleen of a man with fever of several years’ duration.
Brucella organisms that survive the action of polymorphonuclear leukocytes are ingested by macrophages and become localized in the organs of the reticuloendothelial system.
Image 21.2
Brucella melitensis colonies. Brucella species colony characteristics: Fastidious organism and colonies usually are not visible at 24 hours.
Brucella grows slowly on most standard laboratory media (eg, sheep blood, chocolate, and trypticase soy agars). Pinpoint, smooth, translucent, nonhemolytic colonies are shown at 48 hours of incubation. Courtesy of Centers for Disease Control and Prevention/Courtesy of Larry Stauffer, Oregon State Public Health Laboratory.
72 BruCELLOSiS
Image 21.3
Brucellosis. Number of reported cases, by year—united States, 1982–2012. Courtesy of Morbidity and Mortality Weekly Report.
Image 21.4
Brucellosis. Number of reported cases—united States and uS territories, 2012. Courtesy of Morbidity and Mortality Weekly Report.
BURKHOLDERIA iNFECTiONS 73
22
Burkholderia Infections
Clinical Manifestations
Burkholderia cepacia complex has been associ- ated with infections in individuals with cystic fibrosis, chronic granulomatous disease, hemo- globinopathies, or malignant neoplasms and in very preterm neonates. Airway infections in people with cystic fibrosis usually occur later in the course of disease, after bronchiectasis has occurred. Patients with cystic fibrosis can become chronically infected with no change in the rate of pulmonary decompensation and can experience an accelerated decline or have an unexpectedly rapid deterioration in clinical status that results in death. In patients with chronic granulomatous disease, pneumonia is the most common manifestation of B cepacia complex infection; lymphadenitis also occurs.
Disease onset is insidious, with low-grade fever early in the course and systemic effects occur- ring 3 to 4 weeks later. Pleural effusions are common, and lung abscesses can occur. Health care–associated infections, including wound and urinary tract infections and pneumonia, also have been reported, and clusters of disease have been associated with contaminated nasal sprays, mouthwash, and sublingual probes.
Burkholderia pseudomallei is the cause of melioidosis. Its geographic range is expanding, and disease is now known to be endemic in Southeast Asia, northern Australia, areas of the Indian Subcontinent, southern China, Hong Kong, Taiwan, several Pacific and Indian Ocean islands, and some areas of South and Central America. Melioidosis can occur in the United States, usually among travelers return- ing from areas with endemic disease. Melioi- dosis can be asymptomatic and can manifest as a localized infection or present as fulminant septicemia. More than half of individuals with melioidosis are bacteremic at presentation.
Pneumonia is the most commonly reported clinical manifestation of melioidosis. Genito- urinary infections, including prostatic abscesses, skin infections, septic arthritis, and osteomyelitis, and central nervous system involvement, including brain abscesses, are also frequently identified. Acute suppurative parotitis is a manifestation that occurs
frequently in children in Thailand and Cambo- dia but occurs less often in children in other endemic areas. Localized infection is usually nonfatal. In severe cutaneous infection, necro- tizing fasciitis has been reported. In dissemi- nated infection, hepatic and splenic abscesses can occur, and relapses are common without prolonged therapy.
Etiology
The Burkholderia genus comprises more than 40 species that are nutritionally diverse, oxidase- and catalase-producing, nonlactose- fermenting, gram-negative bacilli. B cepacia complex comprises at least 17 species. Addi- tional members of the complex continue to be identified but are rare human pathogens.
Other clinically important species of Burkholderia include B pseudomallei, Burkholderia gladioli, and Burkholderia mallei (the agent responsible for glanders).
Burkholderia thailandensis and Burkholderia oklahomensis are rare human pathogens.
Epidemiology
Burkholderia species are environmentally derived water- and soilborne organisms that can survive for prolonged periods in a moist environment. Depending on the species, transmission can occur from other people (person to person), contact with contaminated fomites, and exposure to environmental sources. Epidemiologic studies of recreational camps and social events attended by people with cystic fibrosis from different geographic areas have documented person-to-person spread of B cepacia complex. The source of acquisition of B cepacia complex by patients with chronic granulomatous disease has not been identified. Health care–associated spread of B cepacia complex is most often associated with contamination of disinfectant solutions used to clean reusable patient equipment, such as bronchoscopes and pressure transducers, or to disinfect skin. Contaminated medical products, including mouthwash and inhaled medications, have been identified as a cause of multistate outbreaks of colonization and infec- tion. B gladioli has been isolated from sputum of people with cystic fibrosis and may be mis- taken for B cepacia. The clinical significance of B gladioli in cystic fibrosis is not known.
74 BURKHOLDERIA iNFECTiONS
Image 22.1
Scanning electron micrograph of Burkholderia cepacia. Burkholderia infections often have an insidious onset, and B cepacia is a nosocomial pathogen. Courtesy of Centers for Disease Control and Prevention/Janice Haney Carr.
In areas with highly endemic infection, B pseudomallei is acquired early in life, with the highest seroconversion rates between 6 and 42 months of age. Melioidosis is seasonal, with more than 75% of cases occurring during the rainy season. Disease can be acquired by direct inhalation of aerosolized organisms or dust particles containing organisms, per- cutaneous or wound inoculation with con- taminated soil or water, or ingestion of contami nated soil, water, or food. People can also become infected as a result of laboratory exposures when proper techniques or proper personal protective equipment guidelines are not followed. Symptomatic infection can occur in infants 1 year or younger, with pneumonia and parotitis reported in infants as young as 8 months. Risk factors for melioidosis include frequent contact with soil and water as well as under lying chronic disease, such as diabetes mellitus, renal insufficiency, chronic pulmonary disease, thalassemia, and immunosuppression not related to HIV infection. B pseudomallei has also been reported to cause pulmonary infection in people with cystic fibrosis and septicemia in children with chronic granulo- matous disease.
Incubation Period
Melioidosis, 1 to 21 days (median, 9 days), but can be prolonged (years).
Diagnostic Tests
Isolation of B cepacia complex infection from appropriate specimens is diagnostic. In cystic fibrosis airway infection, culture of sputum on selective agar is recommended to decrease the potential for overgrowth by mucoid Pseudomo
nas aeruginosa. Confirmation of identification of B cepacia complex species by polymerase chain reaction assay or mass spectroscopy is
recommended. Definitive diagnosis of melioi- dosis is made by isolation of B pseudomallei from blood or other infected sites. The likeli- hood of successfully isolating the organism is increased by culture of sputum, throat, and rectum and ulcer or skin lesion specimens. A direct polymerase chain reaction assay may provide a more rapid result than culture but is less sensitive, especially when performed on blood; it is not recommended for routine use.
Serologic testing is not adequate for diagnosis in endemic areas because of high background seropositivity. However, a positive result by the indirect hemagglutination assay for a traveler who has returned from an area with endemic infection may support the diagnosis of melioi- dosis; definitive diagnosis still requires isola- tion of B pseudomallei from an infected site.
Treatment
Meropenem is the agent most active against most B cepacia complex isolates, although other drugs that may be effective include imipenem, trimethoprim-sulfamethoxazole, ceftazidime, doxycycline, and chlorampheni- col. Some experts recommend combinations of antimicrobial agents that provide synergistic activity against B cepacia complex. The drugs of choice for initial treatment of melioidosis depend on the type of clinical infection, sus- ceptibility testing, and presence of comor- bidities in the patient (eg, diabetes, liver or renal disease, cancer, hemoglobinopathies, cystic fibrosis). Treatment of severe invasive infection should include meropenem, imipenem, or ceftazidime (rare resistance) for a minimum of 10 to 14 days. After acute therapy is completed, oral eradication therapy with trimethoprim- sulfamethoxazole for 3 to 6 months is recom- mended to reduce recurrence.
BURKHOLDERIA iNFECTiONS 75
Image 22.2
This photograph depicts the colonial morphology displayed by gram-negative Burkholderia pseudomallei bacteria, which was grown on a medium of chocolate agar, for a 72-hour period, at a temperature of 37°C (98.6°F). Courtesy of Centers for Disease Control and Prevention/
Dr Todd Parker, Audra marsh.
Image 22.3
Endemicity of melioidosis infection. Centers for Disease Control and Prevention National Center for Emerging and Zoonotic infectious Diseases (NCEZiD) Division of Global migration and Quarantine (DGmQ).
Image 22.4
Burkholderia cepacia on Burkholderia selective agar. With vancomycin, gentamicin, and poly myxin B, this agar is used for the isolation of B cepacia complex from respiratory secretions of patients with cystic fibrosis. Growth of the organism turns the medium from orange to yellow, and colonies are surrounded by a pink-yellow zone in the medium. Growth may require up to 72 hours of incubation.
Courtesy of Julia rosebush, DO; robert Jerris, PhD; and Theresa Stanley, m(ASCP).
76 CAMPYLOBACTER iNFECTiONS
23
Campylobacter Infections
Clinical Manifestations
Predominant symptoms of Campylobacter infections include diarrhea, abdominal pain, malaise, and fever. Stools can contain visible or occult blood. In neonates and young infants, bloody diarrhea without fever can be the only manifestation of infection. Pronounced fevers in children can result in febrile seizures that can occur before gastrointestinal tract symp- toms. Abdominal pain can mimic that pro- duced by appendicitis or intussusception.
Mild infection lasts 1 or 2 days and resembles viral gastroenteritis. Most patients recover in less than 1 week, but 10% to 20% have a relapse or a prolonged or severe illness. Severe or per- sistent infection can mimic acute inflamma- tory bowel disease. Bacteremia is uncommon but can occur in neonates and children.
Immunocompromised hosts can have pro- longed, relapsing, or extraintestinal infections, especially with Campylobacter fetus and other Campylobacter species. Immunoreactive complications, such as acute idiopathic poly- neuritis (Guillain-Barré syndrome) (occurring in an estimated 1 per 1,000 persons), Miller Fisher variant of Guillain-Barré syndrome (ophthalmoplegia, areflexia, ataxia), reactive arthritis, Reiter syndrome (arthritis, urethritis, and bilateral conjunctivitis), myocarditis, peri- carditis, and erythema nodosum, can occur during convalescence.
Etiology
Campylobacter species are motile, comma- shaped, gram-negative bacilli. There are 25 species within the genus Campylobacter, but Campylobacter jejuni and Campylobacter coli are the species isolated most commonly from patients with diarrhea. C fetus predomi- nantly causes systemic illness in neonates and debilitated hosts. Other Campylobacter species, including Campylobacter upsaliensis, Campylo
bacter lari, and Campylobacter hyointestinalis, can cause similar diarrheal or systemic ill- nesses in children.
Epidemiology
Data from the Foodborne Diseases Active Surveillance Network (www.cdc.gov/foodnet) indicate that, although incidence decreased in the early 2000s, the 2012 incidence represented a 14% increase over 2006–2008 baseline. Dis- ease incidence has remained stable since 2010–
2012, with 13.8 cases per 100,000 population in 2013. The highest rates of infection occur in children younger than 5 years. Most Campylo
bacter infections are acquired domestically, but it is also the most common cause of diarrhea in returning international travelers. In susceptible people, as few as 500 Campylobacter organisms can cause infection.
The gastrointestinal tracts of domestic and wild birds and animals are reservoirs of the bacteria. C jejuni and C coli have been isolated from feces of 30% to 100% of healthy chickens, turkeys, and water fowl. Poultry carcasses commonly are contaminated. Many farm ani- mals and meat sources can harbor the organ- ism and are potential sources of infection.
Transmission of C jejuni and C coli occurs by ingestion of contaminated food or water or by direct contact with fecal material from infected animals or people. Improperly cooked poultry, untreated water, and unpasteurized milk have been the main vehicles of transmission. Cam
pylobacter infections usually are sporadic;
outbreaks are rare but have occurred among schoolchildren who drank unpasteurized milk, including children who participated in field trips to dairy farms. Person-to-person spread occurs occasionally, particularly among very young children. Uncommonly, outbreaks of diarrhea in child care centers have been reported. Person-to-person transmission has also occurred in neonates of infected mothers and has resulted in health care–associated out- breaks in nurseries. In neonates, C jejuni and C coli usually cause gastroenteritis, whereas C fetus often causes septicemia or meningitis.
Enteritis occurs in people of all ages. Excretion of Campylobacter organisms typically lasts 2 to 3 weeks without treatment but can be as long as 7 weeks.
CAMPYLOBACTER iNFECTiONS 77
Image 23.1
This photomicrograph depicts findings observed in a 48-hour culture of Campylobacter jejuni bacteria revealing characteristic thin-, comma-, or gull winged–shaped forms displayed by this bacterium. C jejuni is a slender, curved, motile rod that is microaerophilic (ie, it has a reduced requirement for oxygen). it is a relatively fragile organism, being sensitive to environmental stresses such as drying, heating, disinfectants, and acidic conditions. Courtesy of Centers for Disease Control and Prevention/robert Weaver, PhD.
Incubation Period 2 to 5 days but can be longer.
Diagnostic Tests
C jejuni and C coli can be cultured from feces, and Campylobacter species, including C fetus, can be cultured from blood. Isolation of C jejuni and C coli from stool specimens requires selective media, microaerobic condi- tions, and an incubation temperature of 42°C (107.6°F). Although other Campylobacter spe- cies are occasionally isolated using routine culture methods, additional methods that use nonselective isolation techniques and increased hydrogen microaerobic conditions are usually required for isolation of species other than C jejuni and C coli. The presence of motile curved, spiral, or S-shaped rods resembling Vibrio cholerae by stool phase contrast or darkfield microscopy can provide rapid, pre- sumptive evidence for Campylobacter species infection directly from fresh stool samples.
This is less sensitive than culture. C jejuni and C coli can be detected directly (but not differ- entiated) by commercially available enzyme immunoassays. False-positive results from these nonculture-based techniques have been reported. Two multiplex nucleic acid amplifi- cation tests that detect Campylobacter species and other gastrointestinal pathogens, including
Salmonella, Shigella, Campylobacter, and Shiga toxin-producing Escherichia coli, recently became available commercially, but data on their performance characteristics are limited.
Treatment
Rehydration is the mainstay of treatment for all children with diarrhea. Azithromycin and erythromycin shorten the duration of illness and excretion of susceptible organisms and prevent relapse when given early in gastrointes- tinal tract infection. Treatment with azithro- mycin or erythromycin usually eradicates the organism from stool within 2 or 3 days. A fluoroquinolone, such as ciprofloxacin, may be effective, but resistance to ciprofloxacin is common (31% of C coli isolates and 22% of C jejuni isolates in the United States in 2010 [www.cdc.gov/NARMS]) If antimicrobial therapy is given for treatment of gastroenteri- tis, the recommended duration is 3 to 5 days.
Antimicrobial agents for bacteremia should be selected on the basis of antimicrobial sus- ceptibility tests. C fetus generally is susceptible to aminoglycosides, extended-spectrum cepha- losporins, meropenem, imipenem, and ampi- cillin. Antimotility agents should not be used because they have been shown to prolong symptoms and may be associated with an increased risk of death.
78 CAMPYLOBACTER iNFECTiONS
Image 23.2
This image of a Gram-stained specimen shows the spiral rods of Campylobacter fetus subsp fetus taken from an 18-hour brain-heart infusion with a 7% addition of rabbit blood agar plate culture. Courtesy of Centers for Disease Control and Prevention.
Image 23.3
Campylobacter fetus. Leifson flagella stain (digitally colorized) showing comma-shaped, gram-negative bacilli. Courtesy of Centers for Disease Control and Prevention.
Image 23.4
monthly distribution of the number of sporadic cases of Campylobacter infections in humans from July 2000 to October 2001 (columns) and of the prevalence of Campylobacter in whole retail chickens from November 2000 to October 2001 (line graph), Quebec. Courtesy of michaud S, ménard S, Arbeit rD.
Campylobacteriosis, Eastern Townships, Québec. Emerg Infect Dis. 2004;10(10):1844–1847.