Bartonellosis (Bartonella Infection) 

Updated: Jun 19, 2019
Author: Kassem A Hammoud, MD; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD 

Overview

Background

Bartonellosis comprises infections caused by pathogens in the genus Bartonella. In 1909, A. L. Barton described organisms that adhered to RBCs. The name Bartonia, later Bartonella bacilliformis, was used for the only member of the group identified before 1993. Rochalimaea (named for Rocha-Lima), a similar group, were recently combined with Bartonella. Although these organisms were originally thought to be rickettsiae, Bartonella bacteria can be grown on artificial media, unlike rickettsiae.

At least a dozen species belong to the genus Bartonella. Three Bartonella species are currently considered important causes of human disease, but other significant human pathogens in this genus were found to causes disease in humans occasionally. In one study, serum specimens from 114 patients hospitalized with a febrile illness were tested with an indirect immunofluorescence assay (IFA) using rodent and human Bartonella pathogens; 5 patients had high-titer seroconversion to rodent-associated Bartonella.[1]

B bacilliformis causes Oroya fever and verruga peruana. Bartonella henselae causes catscratch disease (CSD) and peliosis of the liver (often called bacillary peliosis). Bartonella quintana causes trench fever. Both B henselae and B quintana may cause bacillary angiomatosis, infections in homeless populations, and infections in patients with HIV.

New Bartonella species that may cause human disease include Bartonella vinsonii subspecies berkhoffii, Bartonella clarridgeiae, Bartonella tamiae, Bartonella rochalimae,Bartonella elizabethae, Bartonellakoehlerae, Bartonella grahamii, and Bartonellaalsatica. Candidatus Bartonella mayotimonensis and Candidatus Bartonella melophagi were respectively isolated from the aortic valve of a patient with culture-negative endocarditis and the blood of two patients with symptoms consistent with bartonellosis.[2, 3] Several of these other species are found in animals. Candidatus Bartonella ancashi was isolated from the blood of a patient with verruga peruana in Peru.[4] Numerous other Bartonella species that can potentially cause human disease have been discovered in ticks.

For additional information on emerging and reemerging infectious diseases, see Medscape’s Emerging and Reemerging Infectious Diseases Resource Center.

Pathophysiology

The transmission of Bartonella species occurs by traumatic contact with infected animals or by vectors like cat fleas or other blood-sucking arthropods (eg, sand fly, Phlebotomus for B bacilliformis).

B bacilliformis, which uses a polar flagellum for motility, adheres to and invades RBCs. After entry, the organism replicates in vacuoles. This species also makes an endothelial cell–stimulating factor that causes proliferation of both endothelial cells and blood vessels.

B henselae and B quintana do not bind to intact human erythrocytes in the same way that B bacilliformis does; however, these organisms make a protein binder that adheres to feline RBC membranes, and they penetrate into endothelial cells. Both species also initiate production of an endothelial cell–stimulating factor. Because lysis-centrifugation blood cultures show enhanced isolation of B henselae and B quintana, intracellular forms are most likely present in humans. Erythrocytes may serve as a reservoir for Bartonella species.

B quintana also invades endothelial cells and forms bacterial aggregates that are taken internally by the invasome, a unique phagosomal structure.[5] These proliferate and make intracellular blebs.

Epidemiology

Frequency

United States

Catscratch disease caused by B henselae infection occurs in approximately 1 per 10,000 persons.

B quintana is found worldwide and causes febrile outbreaks. Poor sanitation and lack of personal hygiene strongly correlate with transmission by the body louse Pediculus humanus. B quintana is emerging as a recognized cause of disease among homeless persons and persons with AIDS. Trench fever syndrome is found among people with alcoholism and those who are homeless. Persons who are indigent in inner-city Seattle were evaluated for antibodies to B quintana. Approximately 20% of these people had antibody titers of 1:64 or greater; in comparison, this titer was found in only 2% of blood donors.[6]

International

B bacilliformis transmission is limited to the Andes Mountains at elevations of 1000-3000 meters because of the habitat of the sand fly Phlebotomus, now called Lutzomyia. Outbreaks of B bacilliformis infection occur only in the Andes. Cases elsewhere in the world are found in travelers.

B henselae is found throughout the world in association with both domestic and feral cats. The cat flea Ctenocephalides felis is an arthropod vector. B henselae and other Bartonella species have been isolated from ticks, but their competence in disease transmission is unclear.[7, 8]

One study from Eastern China done on rabies clinic and blood donors (557 patients) found a seroprevalence of about 20%. Patients bitten by a dog had a higher seroprevalence compared with blood donors (27% vs 14%).[9]

B quintana infection has been reported in 16% of homeless hospitalized patients in France.

Other species, such as B clarridgeiae, may be a cause of asymptomatic infection in cats.

Review of studies from the United States, Japan, and France showed a seasonality in cat scratch disease. In the United States, most cases are diagnosed during the last 6 months of the year, in Japan most of the transmission occurs from September to December with a peak in November, and in France most cases were found between September and April with a peak in December. This is likely related to the weather, reproductive behavior of cats, their contact frequency with humans, and flea activity.[10]

Mortality/Morbidity

Catscratch disease usually causes self-limited regional adenopathy. Acute hemiplegia has been reported in an 11-year-old boy.[11] Encephalopathy is the most common neurologic complication but is rare.

B henselae is a common cause of culture-negative endocarditis. Valve replacement is required in approximately 80% of cases, but overall prognosis is good, with survival rates in excess of 80%.[12] In a 2003 article in Medicine by Houpikian and Raoult, Bartonellaendocarditis was associated with B quintana in 75% of cases and with B henselae in 25% of cases. They reported a mortality rate of 7% among 99 patients with Bartonella endocarditis.[13]

Trench fever is a self-limited relapsing febrile illness. Affected persons regularly recover, even without treatment. Liver abscesses and spleen abscesses in the absence of endocarditis in an immunocompetent host have been described.[14]

Disseminated forms of bartonellosis develop in patients infected with HIV. Bacillary angiomatosis and culture-negative endocarditis are caused by B henselae and B quintana. Peliosis hepatis is caused by B henselae. Mortality is low but morbidity is caused by direct organ involvement of bacillary angiomatosis; relapses are common, especially with short courses of treatment.

Carrión disease commonly affects the pediatric population in Peru and Ecuador. Mortality and morbidity of the acute phase vary because of superimposed infections and other complications. Mortality rates associated with the eruptive phase, known as Peruvian wart, are extremely low.[15]

Sex

Manifestations of catscratch disease in pregnant women are the same as in immunocompetent patients. An article by Bilavsky et al reviewed 19 women with the disease. There was no major adverse effect on the pregnancy in all of them except one abortion during the first trimester. Causality to cat scratch disease could not be established. There was no deleterious effects on the newborns or long-term sequelae in patients.[16]

Prognosis

Catscratch disease rarely results in neurologic sequelae. Adenopathy persists for 6-24 months in 20% of patients. After several months, the lesions of visceral organs calcify or resolve.

Trench fever is a nonlethal and self-limiting disease, although relapses and chronic bacteremic states are well known.

Bartonella endocarditis has caused fatalities and usually requires surgical repair. Of 22 cases reported by Raoult and colleagues in 1996, 19 patients underwent valvular surgery, and 6 patients died.[17]

Immunocompromised patients with bacillary angiomatosis or peliosis hepatis respond well to antibiotics. Relapse may occur.

 

Presentation

History

Currently, Bartonella species cause several clinical syndromes, including catscratch disease (with enlarged nodes and other organ involvement), bacteremia, endocarditis, bacillary angiomatosis, peliosis hepatis, Oroya fever, and verruga peruana. The inability to mount an immune response contributes to manifestations observed in immunosuppressed individuals with advanced AIDS and other diseases.

Catscratch disease

Most affected individuals have typical catscratch disease symptoms and present with an enlarged lymph node.

A primary inoculation lesion often develops at the site of a bite or scratch.

A papule or pustule develops 5-10 days after exposure. This lesion may persist for a few weeks.

B henselae DNA may be chronically shed into peripheral blood during the natural course of catscratch disease.[18]

Bacteremia and systemic illnesses

Trench fever was described in military personnel during World War I. Urban trench fever is now observed in homeless persons in the United States and Europe.

Symptoms of trench fever begin with chills and fever after an incubation period of a few days to a month. Occasionally, the patient experiences only a single febrile episode that lasts 4 or 5 days. More commonly, several episodes of fever occur. Each episode lasts about 5 days, which is the origin of the designation quintana. The patient cycles between severe chills and profuse sweating. In other patients, continuous fever lasts 2-6 weeks.

Associated symptoms include joint and muscle aches, injected conjunctivae, headache, dizziness, and pain behind the eyes. Some patients have diffuse symptoms without fever.

Some cases of trench fever become chronic with debility, with or without fever or aching, and occasionally with hyperexcitability.

In patients with HIV, infection with either B henselae or B quintana causes gradual onset of aching, headache, fatigue, and weight loss. Fever begins later. Persistent bacteremia with B henselae may develop in people with AIDS.

Encephalopathy has been associated mostly with B henselae. Guillain-Barré syndrome, hydrocephalus, and encephalopathy were associated with B quintana acute infection in one case report.[19]

Meningitis due to a "Bartonella washoensis"-like human pathogen was isolated from the blood of a patient with meningitis in California, the patient owned cats, dogs and had contact with squirrels.[20]

Bacillary angiomatosis and peliosis hepatitis

Bacillary angiomatosis was initially described in persons infected with HIV. Typically, it involved the skin and was believed to resemble Kaposi sarcoma but can affect other organs such as the respiratory tract, bone, lymph nodes, gastrointestinal tract, and brain. When the liver or spleen was involved, bacillary peliosis or peliosis hepatis was diagnosed before Bartonella infection was discovered to be the cause.

Symptoms depend on the anatomic site involved and may include fever, tender lymphadenopathy, and skin lesions.

Oroya fever and verruga peruana

Over a century ago, a medical student named Daniel Carrión injected himself with blood from the skin lesion of a patient who had verruga peruana. He developed Oroya fever. Today, Oroya fever and verruga peruana are called Carrión disease. Prior to that time, the relationship between the diseases was unknown.

Bacteremia of Oroya fever begins 3-12 weeks after a bite from an infected sand fly. The illness may range from mild to very severe. In severe cases, fever, chills, headache, sweating, aches, dyspnea, mental status changes, and seizure may occur. Severe disease has an abrupt onset.

Transplant patients

Infection with B henselae is rare but has diverse manifestations. A review of 29 cases found that disseminated disease is common (72%). Fever was reported in 27 patients (93%), lymphadenopathy in 12 patients (41%), and skin lesions in 7 patients (24%).[21]

Physical

Catscratch disease

Enlarged lymph glands develop 1 week to 2 months after exposure. Swollen tender nodes are the usual presenting symptom.

Careful examination of the interdigital spaces, skin creases, and scalp increases the chance of finding the primary inoculation lesion. Inoculation sites other than the skin include the eye and mucous membranes (oral ulcer).

One third to two thirds of patients develop low-grade fever that lasts several days.

B henselae infection is one of the common causes of fever of unknown origin and prolonged fever in children. One study showed that the absence of lymphadenopathy in patients with catscratch disease was closely related to the presence of prolonged fever or systemic complications. Another study of 186 patients with a serological diagnosis of catscratch disease showed that 30 (16.1%) patients had no regional lymphadenopathy. These patients had persistent fever and more frequent systemic complications than patients with lymphadenopathy.[22, 23, 24]

Malaise and fatigue are common. Many patients feel healthy except for the enlarged node or nodes. Patients occasionally have multifocal lymphadenopathy.

Laboratory studies include the following:

  • Diagnosis should be confirmed with demonstration of a 4-fold rise in antibody levels, initially immunoglobulin M (IgM) followed by immunoglobulin G (IgG).

  • Culture confirmation is difficult; PCR is more sensitive.[25]

  • In some patients, hypercalcemia complicates catscratch disease lymphadenopathy via overproduction of vitamin D due to granuloma formation.

Other morbidities include the following:

  • Rarely, catscratch disease spreads and causes granulomatous hepatitis or granulomas in the spleen or bones. Granulomas in the liver or spleen do not enhance with contrast on CT scanning.

  • Parinaud oculoglandular syndrome follows contamination of the eye, often from the patient's own hand. A granulomatous conjunctivitis follows and is associated with enlarged preauricular nodes.

  • Bartonella quintana was isolated from the parotid gland of a patient with acute parotitis.[23]

  • Encephalopathy is an infrequent but important manifestation that occurs in as many as 2-4% of patients with catscratch disease. Several hundred such cases probably occur in the United States each year. Manifestations include generalized headaches, restlessness, combativeness, seizure, and neurologic defects such as aphasia, cranial nerve palsy, Brown-Sequard syndrome, and ataxia. Persistent intellectual impairment has been reported. Cerebral spinal fluid (CSF) cultures and routine studies are not helpful in diagnosis.

  • The ocular manifestations of catscratch disease are numerous. Parinaud oculoglandular syndrome develops in about 2-3% of patients with catscratch disease; posterior segment findings include optic neuropathy, neuroretinitis, and vitreitis, among others. Neuroretinitis (45%) was the most common diagnosis in a study by Sulene et al (62 eyes, 53 patients); only 5 patients had significant complications. At final follow-up, there was no association between visual acuity and systemic antibiotics or steroids use.[26]

  • In neuroretinitis caused by B henselae, a sudden loss of eyesight may be the presenting symptom. The patient usually has a prior flulike syndrome or enlarged nodes. A common examination finding is papilledema with a starburst appearance but the abscence doesn't exclude the diagnosis. A recent report described a 10-year-old girl with catscratch disease who developed a macular hole 12 days after presentation with neuroretinitis in association with a posterior vitreous detachment.[27] Neuroretinitis is usually confirmed based on titers, but, on occasion, retinal biopsy with histopathology may prove helpful. Neuroretinitis usually resolves spontaneously except in immunocompromised patients. Multifocal chorioretinal lesions have also been described.[28]

  • Transverse myelitis was described in 3 patients with catscratch diseases.[29] One case report described a 40-year-old patient with chronic vasculitis and polyneuropathy associated with bartonellosis.[30]

  • Osteomyelitis is a rare manifestation, occurring in 0.2–0.3% of patients with catscratch disease; the most commonly involved site is the spine, but it can be multifocal. Medical therapy with antibiotics is very effective. Maman et al found that, among 913 patients with catscratch disease, 10.5% had musculoskeletal manifestations (myalgia, arthralgia/arthritis, neuralgia, tendinitis, osteomyelitis).[31]

  • One study from Italy reviewed 74 cases of catscratch disease. Atypical presentation was common (24.3%) and included ocular papillitis, maculopapular eruptions, vertebral infection, pulmonary infiltrates, and granulomatous hepatitis.[32]

Bacteremia

Findings include injected conjunctivae, nystagmus, hepatosplenomegaly, lymphadenopathy, and a maculopapular rash.

Muscles or joints may be tender.

Laboratory studies include the following:

  • Patients typically exhibit increased leukocytes with occasional thrombocytopenia or albuminuria. Bacteremia is not usually detected.

  • Patients with prolonged bacteremia may have culture-negative endocarditis because Bartonella species do not grow on standard blood culture media. Special media must be used. B henselae and B quintana infections can cause culture-negative endocarditis. Bartonella alsatica was isolated from the valve of a patient with endocarditis.[33] Most cases of Bartonella endocarditis involve native valves, but infection of prosthetic valves is possible.[34]

  • Antibody titers are helpful in confirming the diagnosis.

As expected, persons with alcoholism and those who are homeless typically develop B quintana endocarditis (75% of cases), while persons with exposure to cats are more likely to harbor B henselae (25% of cases). Other Bartonella species are rarely implicated. Although many children are frequently exposed to cats, even those with catscratch disease rarely develop Bartonella endocarditis.

Bacillary angiomatosis and peliosis hepatitis

Examination findings include purple to red-black, raised, palpable skin lesions.

When the liver, lymph node, or spleen is involved, it may be enlarged.

Laboratory studies include the following:

  • Patients should undergo HIV antibody testing and CD4+ lymphocyte assessment.

  • Patients typically have anemia and elevated levels of serum alkaline phosphatase.

Oroya fever and verruga peruana

Untreated patients have a high case-fatality rate. Survivors may be more susceptible to salmonellosis or toxoplasmosis during the convalescent period.

Verruga peruana lesions develop as crops with onset weeks to months later in untreated survivors. These lesions begin as small nodules and subsequently grow. Highly vascular mulaire lesions then form and begin to ulcerate, bleed, and heal via fibrosis over several months. Various stages of small to larger nodules, mulaire lesions, and fibrosis may occur simultaneously.

Laboratory studies include the following:

  • Hemolytic anemia, thrombocytopenia, and elevated values on liver function studies are common.

  • Survivors may develop persistent bacteremia.

Causes

Catscratch disease

In the United States, catscratch disease is the most common type of bartonellosis.

The clinical syndrome has been recognized for more than a century, but the etiology of this condition was confirmed only in the past decade. Confirmation involved isolating Bartonella species from cats and their fleas, showing an antibody titer rise in patients with the disease, and demonstrating the presence of organisms in biopsy samples through culture and PCR.

Occasional cases are negative for B henselae antibodies. In these instances, rare causes of catscratch disease such as B clarridgeiae or Afipia felis should be considered.

Bacteremia 

Bacteremia may occur with either B henselae or B quintana infection and may result in disseminated diseases. Other species of Bartonella have occasionally been associated with bacteremia.

Oroya fever and verruga peruana

Oroya fever and verruga peruana are manifestations of B bacilliformis infection. These diseases are not found in the United States, but they are common in the Peruvian Andes. Verruga peruana is characterized by subcutaneous nodules consisting of neovascularization, somewhat similar to bacillary angiomatosis.

 

DDx

Diagnostic Considerations

 

Catscratch disease: Consider other causes of enlarged lymph nodes, such as localized infections with regional node swelling and systemic diseases. Examples include lymphoma, leukemia, other neoplasms, fungal infection, tularemia, tuberculosis, plague, lymphogranuloma venereum (LGV), AIDS, toxoplasmosis, and viral infection such as Ebstein-Barr virus infection and syphilis.

Bacteremia and systemic illnesses: Culture-negative endocarditis is always difficult to diagnose. Consider this diagnosis when the Duke criteria for endocarditis are present with negative findings on routine blood cultures. If bartonellosis is suspected, obtain antibody titers for B henselae and B quintana. Other causes of culture-negative endocarditis that merit consideration include legionellosis, Q fever, HACEK group infections (Haemophilus parainfluenzae, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens,Kingella kingae), and fastidious or slowly growing streptococci.

Bacillary angiomatosis: These lesions are often dark purple and resemble Kaposi sarcoma, pyogenic granuloma, or verruga peruana.

Oroya fever and verruga peruana: Febrile patients who have returned from travel to a developing country mandate consideration of a rather large number of possible illnesses depending on the itinerary, activities, and potential for exposures. Serious illnesses to consider include Dengue fever, malaria, tuberculosis, and babesiosis.

Differential Diagnoses

 

Workup

Laboratory Studies

Stains

Microscopic examination of Giemsa-stained blood smears is used to detect B bacilliformis in patients who may have Oroya fever.

Organisms are rod-shaped and slightly curved, similar to Campylobacter or Helicobacter species.

B bacilliformis organisms often appear to be adherent to erythrocytes, but they may actually be inside erythrocytes.

Other Bartonella species are visible only with silver stains (eg, Warthin-Starry, Steiner, Dieterle), if they stain at all. Bacillary forms also exist. These stains are not specific.

Immunostaining can also aid in the diagnosis of early lesions or atypical manifestations of catscratch disease. Capnetti at al[35] found that immunohistochemical analysis was positive in 25% of cases, PCR in 38% of cases, and Steiner silver stain in 46% of cases of 22 patients with lymphadenopathy and histopathological findings compatible with catscratch disease.

Late in the course of B henselae infection, organisms may not be found in areas of necrotizing granulomas.

Cultures

Culture for Bartonella bacteria is not recommended for routine cases of patients with catscratch disease lymphadenopathy.

Cultures may be useful in patients who have other manifestations of either B henselae or B quintana infection, including fever of unknown origin, neuroretinitis, encephalitis, culture-negative endocarditis, and peliosis or bacillary angiomatosis. Fresh media is required to increase the chance of isolation.

A recent study suggests a novel chemically modified liquid medium that supports the growth of 7 Bartonella species.[36]

A 2016 study showed that a serum-free media using glucose, sucrose, and hemin as supplements was equivalent to the commercially available media but was easier to prepare.[37]

The lysis-centrifugation system (Isolator) is recommended for blood cultures.

Minced tissues may be cultured on chocolate agar plates in a humid atmosphere with carbon dioxide to facilitate growth.

Antibiotic susceptibility is not routinely tested in patients with bartonellosis because susceptibility studies may fail to predict response to therapy.

Serologic testing

Serologic testing is the most cost-effective method to confirm the diagnosis in most patients with bartonellosis; however, serologic testing can provide negative results or can be otherwise nondiagnostic in immunocompromised patients. In transplant patients, serology was positive on all 23 patients who were tested.[21]

For catscratch disease and CNS or eye infections, serologic testing provides helpful data. Cross-reactions occur between antibodies for B henselae and B quintana and with both Chlamydia species and Coxiella burnetii.[38]

Some studies have shown that Western immunoblotting appears to have very high sensitivity and specificity for diagnosing Bartonella endocarditis.[13]

An IgM titer of 1:16 or greater is usually considered evidence for early recent Bartonella infection. IgM levels may stay elevated for about 3 months in 50% of patients. A positive IgM finding supports the diagnosis, but sensitivity was low (43%) in one study.[39]

An IgG titer of greater than 1:256 is considered evidence of current or past Bartonella infection. Titers of 1:64 to 1:128 are considered equivocal. A titer of 1:800 or more for IgG antibodies to either B henselae or B quintana has a positive predictive value of 0.810 for the detection of chronic bartonellosis in the general population and a value of 0.955 for the detection of bartonellosis among patients with endocarditis.[40]

Patients with delayed decreases in antibody titers may be at risk for endocarditis relapse. When clinical suspicion is high, titers should be repeated in 10-14 days for comparison.

Evidence shows that some patients never mount a detectable antibody response. The serology results of some patients remain positive long after exposure and recovery from their illness.

Polymerase chain reaction

PCR is a molecular technique that involves amplification of Bartonella species genes.

PCR-based detection of various target genes of Bartonella species in tissue specimens is widely accepted in diagnosing catscratch disease and bacillary angiomatosis, but the results rely heavily on the quality of the laboratory in which the assays are conducted.

In cases of suspected Bartonella endocarditis, PCR on cardiac valve tissue is very sensitive and is not affected by antibiotics treatment prior to surgery.

Because of the cross-reactivity between Bartonella species and other bacteria, PCR analysis of tissue and body fluid is the most specific test, especially in identifying distinct genotypes among Bartonella species.

PCR has played an important role in the diagnosis of Bartonella endocarditis. This test amplifies a 296–base-pair fragment of the 16S ribosomal RNA. Investigators reported PCR results that were positive for Bartonella on cardiac valve tissue in more than 95% of patients with Bartonella endocarditis in one study, despite the fact that more than 60% of these patients underwent valve analyzation following the receipt of antibiotics.

A 2017 study found that the sensitivity of Bartonella PCR on valve tissue was 92% (48/52) compared to 33% (20/60) in blood and 36% (25/70) in serum.[41]

Imaging Studies

CT scanning of the chest and abdomen may reveal mediastinal, retroperitoneal, or mesenteric lymph node enlargement.

CT scanning or ultrasonography of the abdomen can demonstrate multiple hypodense lesions in the liver and/or spleen in patients with catscratch disease

In patients with bacillary angiomatosis/peliosis, CT scanning or MRI of the involved organ shows the enhancing lesions (eg, brain, liver). Radiography of the bone may show osteolytic lesions and bone destruction.

According to some reports, patients with catscratch disease may require echocardiography to assess for valvular lesions. Patients with valvulopathy and catscratch disease are at risk for Bartonella endocarditis.

Other Tests

The catscratch disease skin test is helpful. However, this test may transmit other infectious agents, as it is derived from human pus.

Silver stains and PCR can be performed on pus or tissue collected  via fine-needle aspiration or biopsy.

Histologic Findings

Catscratch disease: Lymph node biopsy demonstrates granulomas with stellate necrosis, which are characteristic of catscratch disease. Silver stains, such as Dieterle or Warthin-Starry, may show bacilli.

Bacillary angiomatosis and peliosis hepatitis: Both of these disorders show blood vessel proliferation. Bacillary angiomatosis refers to vascular tumors that readily bleed when cut. The microscopic appearance of neovascular proliferation is diagnostic. Silver stains may demonstrate clusters of Bartonella bacilli. Peliosis refers to blood-filled cystic lesions that may be microscopic or up to a few millimeters in diameter. These lesions are characteristically found in the liver but are occasionally found in the spleen. Bacilli may be visible on electron microscopy.

 

Treatment

Medical Care

Catscratch disease

Several therapies have been successful. Whether therapy should be provided at all is unclear because catscratch disease is ordinarily a self-limited condition that lasts weeks to months. Therapy is typically provided because of patient concerns about tender nodes and because early treatment is believed to reduce the possibility of disseminated complications.

Cost-effective pharmaceutical choices include erythromycin or doxycycline. Azithromycin has been shown to be more effective than placebo in resolving lymphadenopathy; some consider azithromycin to be the drug of choice.

If the initial therapeutic choice appears unsuccessful after 2-3 weeks, consider switching to azithromycin, co-trimoxazole, or a quinolone antibiotic. Rifampin in combination with another drug, or the use of gentamicin, may be considered in some situations.

The usual duration of therapy is 3-6 weeks. Patients who are bacteremic require at least 4 weeks of therapy. Patients with HIV and other immunocompromising diseases require more prolonged therapy. Patients who have vegetations due to bartonellosis often require valve replacement. An aminoglycoside for at least 14 days should be included in the treatment of Bartonella endocarditis.[42] in combination with doxycycline for at least 6 weeks.

No definitive therapeutic study of CNS bartonellosis or neuroretinitis has been performed, but treating these patients seems prudent. Agents that penetrate the CNS or eye are favored, including doxycycline or azithromycin possibly with rifampin, clarithromycin, or a newer fluoroquinolone antibiotic. A combination of 2 drugs is favored because this may speed healing and because no single agent has been found to cure all cases in which it was used. Data from the literature do not support the use of corticosteroids.

A meta-analysis found 2 studies; one was a randomized controlled study and the other was an observational study. No antibiotic regimen was shown to be beneficial in improving the cure rate or time to achieve cure.[43]

B quintana infection

For bacteremia or trench fever, patients should be administered a trial of doxycycline 100 mg orally twice daily for at least 4 weeks. A longer duration of therapy should be considered in immunocompromised patients. In addition, when the liver or other organs are involved, the duration of therapy is typically longer.

Bacillary angiomatosis

In persons with AIDS and bacillary angiomatosis, the primary pharmaceutical choices include erythromycin, doxycycline, or more expensive drugs such as azithromycin, clarithromycin, or a fluoroquinolone.

Doxycycline combined with rifampin is effective in patients with severe disease. Such patients often require extended treatment (≥3 mo).

Antiretroviral therapy is essential in patient with AIDS in order to improve the immune response and prevent relapses.

B bacilliformis infection

Chloramphenicol has been established as therapy in developing countries, but ciprofloxacin or doxycycline could be used.

If the initial phase (Oroya fever) is not treated, mortality can be higher than 40%.[44]

Duration of therapy should be at least 1 week, and longer courses may be required.

Surgical Care

In an editorial entitled "Bartonellosis: light and shadows in diagnostic and therapeutic issues" in Clinical Microbiology and Infection (2005), Manfredi et al wrote, "The role of surgical debridement and the unpredictable activity of antimicrobial agents warrant further investigation." The authors go on to point out that "The need for, selection and duration of antimicrobial therapy for CSD remain contentious. Suppurative nodes that become tense and painful should be drained, but incision of non-suppurative lesions should be avoided, as chronic draining fistulae or compromised healing may result."[45]

Consultations

See the list below:

  • Infectious diseases specialist

  • Possible consultation with a surgeon or interventional radiology for biopsy or drainage

Prevention

B bacilliformis and B quintana infections: Prevention is best achieved by avoiding the circumstances in which exposure to their arthropod vectors occurs. B bacilliformis transmission is limited to the Andes Mountains at elevations of 1000-3000 meters because of the habitat of the sand fly Phlebotomus, now called Lutzomyia. Outbreaks occur only in the Andes. B quintana is found worldwide and causes febrile outbreaks. Poor sanitation and lack of personal hygiene strongly correlate with transmission by the body louse Pediculus humanus.

B henselae infection: B henselae is found throughout the world in association with both domestic and feral cats. Prevention is achieved by avoiding interactions with cats that might result in scratches, bites, or licks, especially kittens, cats with fleas, and cats that are allowed outdoors.

 

Medication

Medication Summary

Bartonellosis is generally treated with macrolides, tetracyclines, aminoglycosides, or chloramphenicol. Chloramphenicol is not usually used to treat either B henselae or B quintana infection, although it has been used to treat B bacilliformis infection. Chloramphenicol has been primarily used to treat Oroya fever.

Duration of therapy is commonly at least 3 weeks. Patients should be monitored for evidence of response and drug toxicity. Because these infections often fail to respond to therapy or patients experience relapse later, switching to antibiotics from other classes (eg, erythromycin, clarithromycin, azithromycin, trimethoprim and sulfamethoxazole, or ciprofloxacin) may be needed. Gentamicin may also be effective.

Longer duration of therapy, from 3 weeks to 2 months, may be required for patients who have peliosis hepatis or disseminated disease, including bacteremia.

A culture-negative endocarditis treatment regimen should include an aminoglycoside (gentamicin) for 2 weeks and ceftriaxone with or without doxycycline for 6 weeks.

If bartonellosis is proven, the guidelines recommend using a regimen consisting of doxycycline for at least 6 weeks plus gentamicin (1 mg/kg IV q8h for 14 d).

Valve replacement is required in approximately 80% of cases, but overall prognosis is good, with survival rates of 80%.

Patients in the acute phase of Carrión disease should receive ciprofloxacin and, alternatively, chloramphenicol plus penicillin G. Patients in the eruptive phase of the disease should receive rifampin and, alternatively, azithromycin or erythromycin.

Antibiotics

Class Summary

Therapy must be comprehensive and cover all likely pathogens in the context of the clinical setting.

Doxycycline (Vibramycin)

Inhibits protein synthesis and bacterial growth by binding to 30S, and possibly 50S, ribosomal subunits of susceptible bacteria. For B quintana infection, bacillary angiomatosis, peliosis hepatitis, and AIDS.

Erythromycin (EES, E-Mycin, Eryc)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Azithromycin (Zithromax)

Treats mild-to-moderate microbial infections.

Clarithromycin (Biaxin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Ciprofloxacin (Cipro)

Fluoroquinolone with activity against Pseudomonas species, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth.

Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

Chloramphenicol (Chloromycetin)

Binds to 50S ribosomal subunits and inhibits bacterial growth by hindering protein synthesis. Effective against gram-negative and gram-positive bacteria.

Gentamicin (Garamycin)

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and another agent that covers anaerobes.

 

Questions & Answers

Overview

What is bartonellosis (Bartonella infection)?

What is the pathophysiology of bartonellosis (Bartonella infection)?

What is the prevalence of bartonellosis (Bartonella infection) in the US?

What is the global prevalence of bartonellosis (Bartonella infection)?

What is the mortality and morbidity associated with bartonellosis (Bartonella infection)?

What are the sexual predilections of bartonellosis (Bartonella infection)?

What is the prognosis of bartonellosis (Bartonella infection)?

Presentation

Which clinical history findings are characteristic of bartonellosis (Bartonella infection)?

Which clinical history findings are characteristic of bartonellosis (Bartonella infection)-related catscratch disease?

Which clinical history findings are characteristic of bartonellosis (Bartonella infection)-related trench fever?

Which clinical history findings are characteristic of bartonellosis (Bartonella infection)-related bacteremia in patients with HIV/AIDS?

Which clinical history findings are characteristic of bartonellosis (Bartonella infection)-related encephalopathy?

Which clinical history findings are characteristic of bartonellosis (Bartonella infection)-related meningitis?

Which clinical history findings are characteristic of bartonellosis (Bartonella infection)-related bacillary angiomatosis and peliosis hepatis?

Which clinical history findings are characteristic of bartonellosis (Bartonella infection)-related Oroya fever and verruga peruana?

Which clinical history findings are characteristic of bartonellosis (Bartonella infection) in transplant patients?

Which physical findings are characteristic of bartonellosis (Bartonella infection)-related catscratch disease?

What is the role of lab testing in the diagnosis of bartonellosis (Bartonella infection)-related catscratch disease?

What are the morbidities associated with bartonellosis (Bartonella infection)-related catscratch disease?

Which physical findings are characteristic of bartonellosis (Bartonella infection)-related bacteremia?

What is the role of lab testing in the diagnosis of bartonellosis (Bartonella infection)-related bacteremia?

Which physical findings are characteristic of bartonellosis (Bartonella infection)-related bacillary angiomatosis and peliosis hepatitis?

Which physical findings are characteristic of bartonellosis (Bartonella infection)-related Oroya fever and verruga peruana?

Which Bartonella species cause catscratch disease?

Which Bartonella species cause bacteremia?

Which Bartonella species cause Oroya fever and verruga peruana?

DDX

Which conditions should be included in the differential diagnoses of bartonellosis (Bartonella infection)-related catscratch disease?

Which conditions should be included in the differential diagnoses of bartonellosis (Bartonella infection)-related bacteremia?

Which conditions should be included in the differential diagnoses of bacillary angiomatosis associated with bartonellosis (Bartonella infection)?

Which conditions should be included in the differential diagnoses of bartonellosis (Bartonella infection)-related Oroya fever and verruga peruana?

What are the differential diagnoses for Bartonellosis (Bartonella Infection)?

Workup

What is the role of stains in the diagnosis of bartonellosis (Bartonella infection)?

What is the role of cultures in the diagnosis of bartonellosis (Bartonella infection)?

What is the role of serologic testing in the diagnosis of bartonellosis (Bartonella infection)?

What is the role of PCR in the diagnosis of bartonellosis (Bartonella infection)?

What is the role of CT scanning in the diagnosis of bartonellosis (Bartonella infection)?

What is the role of skin testing in the diagnosis of bartonellosis (Bartonella infection)?

What is the role of FNA in the diagnosis of bartonellosis (Bartonella infection)?

Which histologic findings are characteristic of bartonellosis (Bartonella infection)?

Treatment

How is bartonellosis (Bartonella infection)-related catscratch disease treated?

How is bartonellosis caused by B quintana infection treated?

How is bartonellosis (Bartonella infection)-related bacillary angiomatosis treated?

How is bartonellosis caused by B bacilliformis infection treated?

What is the role of surgery in the treatment of bartonellosis (Bartonella infection)?

Which specialist consultations are beneficial to patients with bartonellosis (Bartonella infection)?

How is bartonellosis (Bartonella infection) prevented?

Medications

What is the role of medications in the treatment of bartonellosis (Bartonella infection)?

Which medications in the drug class Antibiotics are used in the treatment of Bartonellosis (Bartonella Infection)?