eMedicine Specialties > Infectious Diseases > Bacterial Infections

HACEK Group Infections

Isaac P Humphrey, MD, Assistant Professor of Internal Medicine, Uniformed Services University of the Health Sciences; Clinical Assistant Professor of Internal Medicine, Wright State University Boonshoft School of Medicine
Mirabelle Kelly, MD, Fellow, Department of Microbiology and Infectious Disease, University of Sherbrooke, Canada; Barnett Gibbs, MD, Assistant Chief, Department of Clinical Trials, Walter Reed Army Institute of Research, Infectious Disease Service, National Capital Consortium; Assistant Professor of Medicine, Uniformed Services University of the Health Sciences; Christian P Sinave, MD, Associate Professor, Department of Medical Microbiology and Infectious Diseases, University of Sherbrooke, Canada

Updated: Nov 6, 2009

Introduction

Background

The acronym HACEK refers to a grouping of gram-negative bacilli: Haemophilus species (Haemophilus parainfluenzae, Haemophilus aphrophilus, Haemophilus paraphrophilus), Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species. These organisms share an enhanced capacity to produce endocardial infections. Based on large reviews, HACEK organisms are responsible for approximately 3% of cases of native valve infective endocarditis (IE).¹ They are also the most common cause of gram-negative endocarditis among persons who do not abuse intravenous drugs.

These organisms are found as part of the normal human oral flora. Because of their fastidious and slow growth, they are often a cause of culture-negative endocarditis, although modern culture and genetic identification techniques are challenging this paradigm.²

In addition to cardiac valve infections, this group is also a cause of other infections, including periodontal infections, bacteremia, abscesses, peritonitis, otitis media, conjunctivitis, pneumonia, septic arthritis, osteomyelitis, urinary tract infections, wound infections, and brain abscess.

Pathophysiology

When introduced into healthy tissue, the HACEK group organisms have the potential for abscess formation and invasive disease. In addition, many examples produce vegetations on infected cardiac valves that are complicated by macroemboli. These vegetations are due to the intrinsic properties of the organisms themselves, the significant delay in diagnosis, or a combination of these two factors. Sixty percent of cases of HACEK IE are associated with various types of dental pathology.

Haemophilus species are pleomorphic gram-negative coccobacilli that require X (hemin) and/or V (nicotinamide adenine dinucleotide) factors for isolation. These substances are found naturally in red blood cells. They are responsible for 0.5%-1% of all cases of IE. Of those, 40% are due to H aphrophilus, followed by H parainfluenzae. H influenzae rarely causes IE despite its frequency of being involved in bacteremias. Ten percent of cases involve a second pathogen, usually an alpha-hemolytic Streptococcus or Staphylococcus aureus. Endocarditis due to H parainfluenzae has been increasing in frequency. Of these cases, 45% are associated with oral pathology and 10% are associated with upper respiratory tract infections. In 67% of cases, the mitral valve is involved, and in 17%, the aortic valve is involved. Fifty percent of patients have underlying valvular disease.

Thirty-three percent of cases of H aphrophilus IE are due to dental disease, and 20% are due to sinusitis or otitis media. The mitral valve is involved in 56% of patients, and the aortic valve is involved in 33%. Eighty-eight percent of individuals have underlying cardiac disease. Arterial embolization occurs in 31% of cases of H aphrophilus IE .

A actinomycetemcomitans was first isolated in 1912 from skin lesions associated with Actinobacillus israelii. Growth of this bacillus occurs in trypticase soy broth, where it forms granules that float on top or stick to the container. It is the etiologic agent of localized juvenile periodontitis, one manifestation of early-onset periodontitis (EOP).

EOP includes a spectrum of entities in which severe periodontal attachment loss occurs in children, adolescents, and young adults. The ability of this organism to produce gingivitis is based in great part on its production of a leukotoxin and its ability to invade gingival cells. A actinomycetemcomitans, on its own, can mimic most of the clinical syndromes caused by A israelii. Of patients with A actinomycetemcomitans IE, 86% have underlying heart disease and 25% have infection of a prosthetic valve (usually aortic). The aortic valve is involved in 65%, and the mitral valve is involved in 30%. Arterial embolization occurs in 43% of cases.

As opposed to the other members of the HACEK group, C hominis has been isolated almost exclusively from patients with endocarditis. In addition to being part of the normal flora of the mouth and upper airway, it is isolated from the large bowel. However, most C hominis bloodstream infections are secondary to oral pathology. They are gram-negative or gram-variable pleomorphic rods with bulbous swelling of both ends that are characteristically grouped in chains, clusters, or rosettes. Seventy-five percent of cases have underlying heart disease, with 43% involving the mitral valve and 36% the aortic valve. Arterial embolization is documented in 40% of patients.

E corrodens takes its name from its ability to corrode (or pit) the agar during growth. It is a gram-negative pleomorphic, often coccobacillary, rod that exudes a chlorine bleach odor. It is facultatively anaerobic. It is part of the oral flora and many other mucosal surfaces.

E corrodens is usually isolated with other organisms, especially strains of streptococci. This organism is a well-recognized cause of cellulitis resulting from human bites and clenched-fist injuries. It has also been found to be a common cause of soft-tissue infections and endocarditis in drug users. This association may arise from the habit of intravenous drug abusers to lick their needles for good luck. These infections are often complicated by osteomyelitis of the underlying bones. It may produce various pulmonary infections (eg, empyema, pneumonia, septic emboli) that mimic those caused by strict anaerobes. Most patients with E corrodens endocarditis have underlying valve lesions. Compared to cases of IE caused by the other members of the HACEK group, the valvular infections of E corrodens are usually due to intravenous drug abuse.

Kingella species are small gram-negative organisms whose shapes range from those of cocci to those of coccobacilli. This organism can also cause pitting of the agar. The Kingella genus includes 3 species: Kingella kingae, Kingella denitrificans, and Kingella indologenes. IE is usually caused by K kingae. Only approximately 20 cases of endocarditis have been described. Unlike with the other HACEK organisms, Kingella IE progresses quite rapidly.

Frequency

United States

In a study performed in 1982, the HACEK organisms were found to be responsible for 57% of endocarditis cases due to gram-negative organisms.³ It is apparent that non-HACEK gram-negative endocarditis is likely increasing in incidence owing to the increased use of endovascular devices.⁴ However, whether the incidence of HACEK group infections is increasing or decreasing is unclear based on the current literature. Reporting of these infections has increased, but this may be due simply to increased awareness of the infections among physicians and laboratory personnel, along with new laboratory techniques. Mayo Clinic data suggest the incidence of the HACEK group endocarditis to be 0.14 per 100,000 patient-years.¹

International

Several reviews of endocarditis in various countries have detailed IE related to the HACEK group of organisms.⁵ However, the incidence in the international community as a whole is unknown.

Mortality/Morbidity

Endocarditis caused by the HACEK organisms is typically subacute, with the exception of H parainfluenzae endocarditis, which may present more acutely.⁶ At the time of presentation, large valvular vegetations are common. Embolization is common and results in significant morbidity.

• Mortality rates range from 10%-40% and may vary by organism. Contemporary case series have suggested a modern mortality risk closer to 10%-15%.¹
• The morbidity of IE caused by the HACEK group is similar to that of other types of endocarditis and includes embolization, local extension into the perivalvular area, congestive heart failure (CHF), and regurgitant valve lesions. Compared with all causes of IE, these organisms may be associated with an increased risk of embolization.⁷

Race

• No racial differences have been reported in endocarditis caused by the HACEK organisms.

Sex

• Older data suggest that HACEK endocarditis has a male predominance. However, there is not enough data available to say that, in the modern era, there is a predilection toward either sex.³

Age

• The great majority of IE cases caused by HACEK organisms have been reported in older adults.

Clinical

History

Most cases of infective endocarditis (IE) caused by the HACEK organisms are subacute. Patients present with progressive symptoms developing over weeks. Some cases have been present for as long as 18 months before the correct diagnosis is made.³ This delay is often due to failure to use special culture techniques.² (See Lab studies.) HACEK IE should be considered in the differential diagnoses of fever of unknown origin.

• Fever is common but may be absent in elderly individuals, immunocompromised patients, or patients taking anti-inflammatory drugs. In some series, it was present in only 50% of cases.³
• Nonspecific symptoms, such as weight loss, anorexia, nausea and vomiting, fatigue, back pain, and night sweats, are common and may lead to a delay in diagnosis.
• Patients may have a history of prior valvular disease.
• A history of prior dental, urologic, and other procedures should be elicited.
• A history of intravenous drug abuse should be elicited.
• A sentinel headache may indicate the impending rupture of a mycotic aneurysm.⁸

Physical

The diagnosis of endocarditis is challenging. The physical findings are often subtle and difficult to identify for many clinicians. Special care should be taken to perform a comprehensive physical examination looking for evidence of endocarditis. Some of the areas to focus on are noted below.⁹

• Heart: A new or changing heart murmur is the most consistent physical finding, but it may be absent, especially in right-sided endocarditis.
• Peripheral
  • Because of the increased use of healthcare and diagnostic imaging, the peripheral manifestations of endocarditis are not seen as commonly as they once were.
  • Examine the patient for clubbing (with or without hypertrophic osteoarthropathy), splinter hemorrhages, mucocutaneous petechiae, Osler nodes, Janeway lesions, and Roth spots.
  • Splenomegaly is common.
• Embolic complications¹⁰
  • A vegetation can embolize to virtually any vessel and can result in various sequelae.
  • Observe for compromise of circulation to the limbs due to embolization.
  • Emboli to the CNS often presents as a focal neurological deficit or a stroke. Emboli to the frontal lobe may be more subtle, causing personality changes or loss of inhibition.⁸
  • Emboli to the kidney may cause flank tenderness, hematuria, and/or oliguria.
  • Embolization to heart vessels can have various manifestations, including acute myocardial infarction and arrhythmia.
  • A large mesenteric embolus can cause bowel ischemia and thus manifest as abdominal pain and tenderness.
  • A right-sided vegetation can embolize to the lung and present similarly to a pulmonary embolus or focal pneumonia.

Causes

• Patients may have a history of a preceding dental, urologic, or gastroenterologic procedure.¹⁰
• A history of intravenous drug use also should be considered because many drug users clean their needles or venipuncture sites with saliva. Among the HACEK organisms, E corrodens is the bacterium that has been most frequently associated with intravenous drug abuse.¹¹
• A history of heart valve abnormalities or the presence of a prosthetic heart valve also predisposes to endocarditis.

Differential Diagnoses

Actinomycosis
Brain Abscess
Fever of Unknown Origin
HACEK Group Infections
Infective Endocarditis

Other Problems to Be Considered

Marantic endocarditis
Collagen vascular disease
Neoplasm
Hypercoagulable states (lupus anticoagulant)

Workup

Laboratory Studies

• When a HACEK organism is suspected, consider consulting a microbiologist so that special attention can be given to the blood culture specimen. Special procedures performed in the microbiology laboratory my improve the chances of isolating the organisms.²
• Although prolonged incubation is commonly recommended in this setting, current research suggests it is the special laboratory procedures, rather than the time of incubation, that matter most.²
• Complete cell count may show anemia with or without reactive thrombocytosis. Total white cell count may or may not be increased.
• Other inflammatory parameters should include erythrocyte sedimentation rate, rheumatoid factor (ie, "the poor man's immune complex"), and C-reactive protein. If positive at the time of diagnosis, they can be used to monitor therapy.

Imaging Studies

• Echocardiography
  • Echocardiography plays an important role in the diagnosis and management of endocarditis. Characteristic vegetations, abscesses, new prosthetic-valve dehiscence, or new regurgitant murmur are 4 powerful identifiers of infective endocarditis (IE) (in combination with other clinical criteria).
  • Transthoracic echocardiography (TTE) has the advantages of being fast and easy to perform. Specificity for vegetations is 98%; however, sensitivity is lower than 60%. TTE views may be inadequate in approximately 20% of the adult population because of obesity, chronic obstructive pulmonary disease, or chest-wall deformities. TTE cannot exclude infection of prosthetic valves, periannular abscess, leaflet perforation, or fistulae.
  • Transesophageal echocardiography has the advantage of having higher sensitivity for vegetations and greater specificity and sensitivity for perivalvular extension than TTE.
  • HACEK group organisms typically produce vegetations that are larger than vegetations found in IE due to other organisms, probably because of the longer mean time to diagnosis.
  • In addition to its diagnostic utility, echocardiography may play a prognostic role. Certain vegetation characteristics are associated with increased risk for embolism and mortality.¹²

Procedures

• An arterial embolectomy, necessary to salvage a limb, may yield a specimen, which, by culture or histological examination, indicates the correct diagnosis.

Histologic Findings

The valvular lesions and vegetations of HACEK IE are very similar to those found in other types of subacute endocarditis, except that the larger size of the vegetations resembles those seen in fungal or staphylococcal disease.¹³

Treatment

Medical Care

• Appropriate antibiotic therapy is central to the management of infective endocarditis (IE) caused by the HACEK organisms (see Medications).
  • Diagnosis should be clearly established before starting treatment because administration of antimicrobial agents to patients with IE before blood cultures are obtained reduces the recovery rate of bacteria by 35%-40%.
  • Older literature suggested that standard beta-lactam antibiotics were the drugs of choice for HACEK infections. However, recent data suggest that beta-lactam resistance is prevalent and that broader-spectrum agents are needed for initial therapy. Based on Infectious Diseases Society of America (IDSA)–endorsed guidelines, ceftriaxone and ampicillin-sulbactam are excellent initial choices.⁷
  • In the case of beta-lactam allergy, a fluoroquinolone (eg, ciprofloxacin, levofloxacin, moxifloxacin) may be used. The clinical data on the use of fluoroquinolones in this setting are limited, so they should be reserved for patients who cannot tolerate the standard regimen.⁷
  • Antibiotic therapy may be fine tuned when susceptibility data for the causative organism are available.
• Complications that arise (eg, heart failure, embolic complications) also require supportive medical therapy.

Surgical Care

• The decision to consider surgical therapy in patients with IE is often challenging and must be made on an individual basis. Below are several accepted indications for surgery in IE.⁷
  • Refractory CHF
  • One or more embolic episode
  • Uncontrolled infection (persistently positive blood cultures after 1 week of therapy)
  • Physiologically significant valve dysfunction as demonstrated by echocardiography: According to the American Heart Association Committee on IE, criteria associated with an increased need for surgical intervention include (1) persistent vegetations after a major systemic embolic episode; (2) anterior mitral valve vegetations larger than 1 cm in diameter; (3) increase in size of vegetations after 1 month of therapy; (4) periannular extension of infection; and (5) valvular dysfunction, perforation, or rupture.
  • Ineffective antimicrobial therapy (usually not the case with HACEK organisms)
  • Resection of mycotic aneurysms
  • Most cases of prosthetic valve endocarditis caused by more resistant organisms (eg, methicillin-resistant S aureus [MRSA], vancomycin-resistant enterococci [VRE], enteric gram-negative bacilli)
  • Local suppurative complications including perivalvular or myocardial abscess

Consultations

Treatment of HACEK endocarditis requires a multidisciplinary approach.

• Consultation with an infectious disease specialist may be helpful for selecting antibiotics, monitoring therapy, and selecting the duration of therapy.
• Consultation with a cardiologist may be helpful, especially if transesophageal echocardiography is needed or if CHF develops.
• Management of large vegetations or mechanical complications warrants a cardiovascular surgeon's advice.
• Consultation with a dentist is indicated if periodontal disease is present.

Diet

No special diet is necessary in patients with HACEK group infections.

Activity

Although there is no evidence-based recommendation for activity levels in patients with endocarditis, it is prudent to keep activity light in the initial phase of treatment.

Medication

Traditionally, treatment for infection with HACEK organisms had been with penicillin or ampicillin alone or in combination with an aminoglycoside. However, resistance due to beta-lactamase has been reported throughout the HACEK group. For the allergic patient or if the organism shows resistance, many other options are available. The decision of which drug to use should be based on susceptibility data, when available.

Empiric therapy with ceftriaxone or ampicillin-sulbactam is the recommended approach. Fluoroquinolones can be used in the case of allergy or intolerance to the recommended regimen. Treatment duration is 4 weeks for native valve disease and 6 weeks for prosthetic valve disease.

Antibiotics

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

Ceftriaxone (Rocephin)

Drug of choice for treatment of endocarditis due to HACEK organisms. Third-generation cephalosporin with broad-spectrum, gram-negative activity. Lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins. No adjustment necessary in persons with renal or hepatic impairment. Dose should be administered postdialysis if undergoing hemodialysis.

Dosing

Adult

2 g IV q24h

Pediatric

100 mg/kg IV q24h

Interactions

Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity; hyperbilirubinemic neonates, particularly those who are premature (reported to displace bilirubin from albumin-binding sites)

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in breastfeeding women and allergy to penicillin; may cause antibiotic-associated colitis or colitis secondary to Clostridium difficile; adverse reactions include rash, diarrhea, eosinophilia, thrombocytosis, leukopenia, elevated transaminases, increased BUN, and local pain and induration at injection site; pseudobiliary lithiasis may require cholecystectomy

Ampicillin and sulbactam (Unasyn)

Drug combination of beta-lactamase inhibitor with ampicillin. Interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.
Covers skin, enteric flora, and anaerobes. Not ideal for nosocomial pathogens.

Dosing

Adult

3 g (2 g ampicillin + 1 g sulbactam) IV q 6h

Pediatric

<3 months: Not established
3 months to 12 years: 300 mg ampicillin/kg/d IV divided q6h
>12-years: Administer as in adults; not to exceed 4 g/d sulbactam or 8 g/d ampicillin

Interactions

Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction

Ciprofloxacin (Cipro)

Alternative to ceftriaxone. Fluoroquinolone with activity against some pseudomonads, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms, but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth.

Dosing

Adult

500 mg PO q12h or 400 mg IV q12h

Pediatric

Not recommended

Interactions

Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT); enteral feedings may decrease plasma concentrations (probably by >30%); nasogastric administration produces greater loss in activity than nasoduodenal administration; discontinued feeding for 1-2 h prior to and after administration; didanosine and sucralfate may decrease effects by approximately 90% if administered concurrently with ciprofloxacin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy; has caused arthropathy in children; green discoloration of teeth has been reported in newborns; rarely causes inflamed and ruptured tendons; CNS stimulation may occur; may cause seizures; avoid in patients with renal insufficiency or CNS disorders

Follow-up

Further Inpatient Care

• Careful clinical observation is the most important aspect of monitoring adequacy of therapy in HACEK group infections.
  • Persistent or recurrent fever may be a sign of treatment failure, but it also may be due to hypersensitivity reactions, thrombophlebitis, or sterile embolization.
  • Observe patients closely for signs of complications, such as embolic events or CHF.
• Repeat blood cultures every 48 hours until they become negative.
• Fever that lasts longer than 10 days after starting appropriate antibiotics should cause concern.
• Causes of persistent fever include drug fever, antibiotic resistance, myocardial or septal abscesses, large vegetations that are difficult to sterilize, and metastatic infection (intracerebral mycotic aneurysms).

Further Outpatient Care

• Relapse may occur during the first 6 months following the end of treatment. Patients should be counseled and observed regarding relapse.

Inpatient & Outpatient Medications

• In general, the entire course should be with intravenous antibiotics. Once the patient is stable and cultures are negative, completing intravenous therapy on an outpatient basis is reasonable. However, even in the outpatient setting, frequent evaluations are necessary to assess for response to therapy and for drug toxicity.
• Although little evidence exists to support its use in this setting, ciprofloxacin could be used in oral form in certain circumstances. However, given the lack of evidence, this be reserved for special circumstances and in consultation with an infectious disease specialist.⁷

Transfer

• If HACEK infection is diagnosed early, managing the infection in a center that does not offer cardiovascular surgery services may be possible. However, consider transfer to a health center with complete cardiac and neurological care for any patient at high risk for complications.
• If the patient is stable, has good social support, and is afebrile with negative blood cultures, outpatient therapy can then be offered for the remainder of the treatment course.

Deterrence/Prevention

• The risk of endocarditis due to HACEK organisms may be reduced by maintenance of good dental hygiene.
• Guidelines for infective endocarditis (IE) prophylaxis prior to dental procedures were updated in 2007. Current recommendations support the use of prophylactic antibiotics for high-risk lesions only.
• Antibiotic prophylaxis should be considered before oral/dental procedures in patients with high-risk cardiac conditions.¹⁴
• High-risk conditions include the following:
  • Prosthetic valves
  • Previous bacterial endocarditis
  • Complex cyanotic congenital heart disease
  • Surgically constructed systemic pulmonary shunts or conduits
  • Valvulopathy in cardiac transplantation recipients

Complications

• Many complications can result from IE, regardless of the causative organisms.
  • CHF is the complication of IE that has the greatest impact on prognosis. It may develop acutely from perforation of a valve leaflet, rupture of an infected chordae, valve obstruction, or because of sudden intracardiac shunts from fistulous tracts. When it appears more insidiously, CHF usually develops during the first month of therapy. Any deterioration in heart function should be taken very seriously because operative mortality increases dramatically after frank ventricular decompensation.
  • Neurologic complications, whether from emboli, abscess, hemorrhage, or arteritis, are the most frequent causes of death in patients with IE. Mycotic aneurysms are usually clinically silent until they rupture. Consider performing a magnetic resonance angiogram or cerebral CT scan to look for aneurysm in patients with subacute IE.
  • Splenic infarctions can occur in more than one third of patients but are often clinically silent.
  • Septic or bland emboli may reach the lung in right-sided endocarditis. These may cause pulmonary infarction, pneumonia, and empyema.

Prognosis

• The prognosis is quite variable, depending on many factors, such as delay in diagnosis, age of the patient, and occurrence of complications. Patients with uncomplicated IE caused by HACEK organisms generally respond well to therapy and have an excellent prognosis.¹

Miscellaneous

Medicolegal Pitfalls

• HACEK group infections are a diagnostic challenge. Infective endocarditis (IE), the most frequent infection caused by these organisms in adults, is often subacute and may present in myriad ways, resulting in a delay in diagnosis. The way to overcome this is to include IE in the differential diagnoses in any patient presenting with nonspecific symptoms, such as weight loss and fatigue, in the presence or absence of fever. Suspicion should be even greater in intravenous drug addicts, patients with periodontitis, and patients with a heart murmur.
• The fastidious nature of these organisms makes microbiological identification difficult. Communication with the medical microbiologist is of important to optimize yield.

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Keywords

species, endocarditis, gram-negative endocarditis

Contributor Information and Disclosures

Author

Isaac P Humphrey, MD, Assistant Professor of Internal Medicine, Uniformed Services University of the Health Sciences; Clinical Assistant Professor of Internal Medicine, Wright State University Boonshoft School of Medicine
Isaac P Humphrey, MD is a member of the following medical societies: American College of Physicians and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Mirabelle Kelly, MD, Fellow, Department of Microbiology and Infectious Disease, University of Sherbrooke, Canada
Mirabelle Kelly, MD is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Barnett Gibbs, MD, Assistant Chief, Department of Clinical Trials, Walter Reed Army Institute of Research, Infectious Disease Service, National Capital Consortium; Assistant Professor of Medicine, Uniformed Services University of the Health Sciences
Disclosure: Nothing to disclose.

Christian P Sinave, MD, Associate Professor, Department of Medical Microbiology and Infectious Diseases, University of Sherbrooke, Canada
Christian P Sinave, MD is a member of the following medical societies: American Society for Microbiology and Canadian Infectious Disease Society
Disclosure: Nothing to disclose.

Medical Editor

Kenneth C Earhart, MD, Deputy Head, Disease Surveillance Program, United States Naval Medical Research Unit #3
Kenneth C Earhart, MD is a member of the following medical societies: American College of Physicians, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and Undersea and Hyperbaric Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

John L Brusch, MD, FACP, Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance
John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

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, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

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