(HOSPITAL ACQUIRED)
(<30 DAYS POST-IMPLANTATION)*
NOTE: *After 30 days postimplantation, the microbiology of prosthetic valve endocarditis increasingly resembles community-acquired native valve endocarditis.
DIAGNOSIS
The typical symptoms of endocarditis are prolonged fever, fatigue, weight loss, and back pain. Patients with this constellation of symptoms should be closely evaluated for cardiac murmurs. Additional findings on physical examination can include Roth spots, Osler nodes, Janeway lesions, splinter hemorrhages, and conjunctival petechiae. These findings are typically only present, however, in patients with subacute disease who have been infected for weeks to months. Patients should be carefully examined for metastatic sites of infection—typical destinations include the brain, vertebrae, joints, liver, spleen, and eye. Draw at least two sets of blood cultures before beginning any empirical antibiotics.
Echocardiography is the test of choice for patients with suspected endocarditis. A transthoracic echocardiogram is a reasonable place to start because it is noninvasive, but endocarditis cannot be excluded until the patient gets a transesophageal echocardiogram. Transthoracic studies are only about 50–60% sensitive compared to transesophageal imaging.
TREATMENT
Consultation with an infectious disease specialist is recommended for all patients with proven endocarditis to help guide management. In general terms, however, treatment is tailored to the antimicrobial susceptibility of the specific pathogen isolated from the patient’s blood or resected valve. Typical agents include penicillin or ceftriaxone for streptococci, with the addition of gentamicin for isolates with partial resistance to penicillin; nafcillin for methicillin-susceptible S. aureus or vancomycin for methicillin-resistant organisms; and a combination of penicillin or vancomycin and gentamicin for enterococcal infections. Patients should have daily blood cultures drawn daily until bacteremia has cleared. The length of treatment varies between 4 and 6 weeks depending on the specific pathogen. The duration of therapy is counted from the first day of negative blood cultures rather than from the first day antibiotics were administered. Some patients require surgical therapy in addition to antibiotics. Indications for surgery include hemodynamic compromise, significant valvular dysfunction, myocardial abscess, and persistently positive blood cultures despite appropriate therapy. In the case of hemodynamic compromise or congestive heart failure, surgery should not be delayed even when signs and symptoms suggest ongoing active infection.
PROPHYLAXIS
Only patients with cardiac conditions associated with a high risk of adverse outcomes from endocarditis are targeted for antibiotic prophylaxis. These include patients with prosthetic valves or prosthetic cardiac repair materials, previous endocarditis, unrepaired or incompletely repaired congenital cyanotic heart disease, and cardiac transplant patients with valve disease. These patients should receive 2 g of amoxicillin 30–60 minutes prior to dental work, respiratory tract procedures that include incision or biopsy, and surgery on infected skin, muscle, or bones. Antibiotic prophylaxis is not recommended for patients with other cardiac conditions (such as mitral valve prolapse) or for any patient undergoing gastrointestinal or genitourinary procedures.
CLOSTRIDIUM DIFFICILE
EPIDEMIOLOGY AND RISK FACTORS
Clostridium difficile is the most frequent pathogen associated with nosocomial diarrhea. The disease has taken on new importance in the past few years as a result of the emergence of a hypervirulent strain associated with a substantially increased risk of colectomy and death. Evaluation of every hospitalized patient with diarrhea should include testing for C. difficile. The major risk factors for C. difficile are antibiotic exposure and hospitalization. Any antibiotic can precipitate C. difficile, including quinolones, cephalosporins, and penicillins as well as clindamycin. Rarely, C. difficile can occur after cancer chemotherapy due to the antimicrobial activity of chemotherapeutic agents.
NOSOCOMIAL TRANSMISSION
Nosocomial transmission of C. difficile is distressingly common because the organism forms spores that are resistant to conventional hospital cleaning agents. Bleach is the only common cleaning agent that kills C. difficile spores. Similarly, alcohol-based hand washes are also ineffective against C. difficile spores. Clinicians need to wash their hands with soap and water for at least 2 minutes to mechanically rid their hands of C. difficile after touching a contaminated patient or environment. Patients suspected of having C. difficile should be isolated from the moment of suspicion to prevent the spread of infection to uninfected patients.
CLINICAL PRESENTATION
The clinical manifestations of C. difficile infection include fever, abdominal cramping or bloating, severe diarrhea, and leukocytosis. Computed tomography findings can include colonic dilatation and colonic wall thickening (Figure 9.1). The organism is difficult to culture, hence diagnosis is accomplished by assaying stool for C. difficile toxins using an enzyme immunoassay or polymerase chain reaction (PCR). The immunoassay has variable sensitivity; thus, a negative test in a patient with a high clinical probability of disease should prompt repeat enzyme immunoassay testing or PCR. Some hospitals begin testing with PCR. About 5% of health community dwellers carry C. difficile in their intestines. Hence, PCR testing should be reserved for patients that have symptoms of invasive disease (i.e., diarrhea) in order to avoid false-positive results. Likewise, “test of cure” is not recommended in patients responding to treatment since the organism often persists after treatment.
Figure 9.1. Severe Clostridium difficile colitis (toxic megacolon).
TREATMENT
The treatment strategy for C. difficile depends on the severity of the infection. Patients with relatively mild disease (diarrhea but minimal abdominal pain, fever, or leukocytosis) can be treated with oral vancomycin or oral metronidazole. A recently added option for treatment is fidaxomicin; it is as effective as vancomycin, but much more expensive. Patients with refractory or severe disease (septic physiology, high fever, severe abdominal pain, marked leukocytosis) should be treated with oral vancomycin along with intravenous metronidazole. A surgeon should be consulted in all patients with severe infection because early colectomy is sometimes the only way to save the life of someone infected with a hypervirulent strain. Consultation with an infectious disease specialist is also advised to guide the management of severe infections.
Up to a third of patients infected with C. difficile will develop one or more recurrent infections. Initial therapy of recurrent infection is typically the same as an initial infection, but preventing further recurrences infections can be very challenging. Potential strategies include prescribing an extended course of vancomycin with gradually increasing intervals between doses, vancomycin pulse therapy, alternative agents such as fidaxomicin, and fecal microbiota transplantation. Consultation with an infectious disease specialist is recommended for patients with recurrent disease.
TRAVEL MEDICINE
PREVENTION
Pre-trip counseling and vaccination are the keystones of travel medicine. Advice and immunizations ought to be tailored to the traveler’s destination, duration of time abroad, and planned activities. First ensure that the patient is up-to-date in routine immunizations such as measles–mumps–rubella, tetanus–diphtheria–acellular pertussis, Haemophilus influenzae, Streptococcus pneumoniae, and influenza. Depending on destination and activities, the patient might also merit vaccines against hepatitis A and B, Neisseria meningitidis, polio, typhoid fever, yellow fever, rabies, and Japanese encephalitis. Travelers to malaria-endemic regions should be offered malaria prophylaxis tailored to the resistance profile of parasites in the traveler’s destination. Clinicians are advised to check the website of the Centers for Disease Control and Prevention (www.cdc.gov/travel) for specific recommendations on vaccines and malaria prophylaxis.
TRAVELER’S DIARRHEA
Diarrhea is the most common illness afflicting travelers to developing countries. Half or more of travelers to developing countries for 2–3 weeks develop diarrhea. The management of diarrhea begins with prevention. Advise travelers to avoid drinking untreated water and eating uncooked produce or vegetables that have come into contact with untreated water. The catch phrase is “peel it, boil it, or don’t eat it.”
Should diarrhea develop, travelers should focus on aggressive self-hydration followed by empiric therapy with a quinolone (e.g., ciprofloxacin, 250 mg twice daily for 1–3 days) or single dose of azithromycin (1000 mg orally). Patients can also take loperamide for symptom relief so long as they are not experiencing fever or hematochezia.
Persistent diarrhea in a returning traveler can be divided into bloody and nonbloody categories. Bloody diarrhea is usually caused by enteroinvasive strains of E. coli, Salmonella, Shigella, Campylobacter, Yersinia, and Entamoeba histolytica. The stool of patients with acute bloody diarrhea should be cultured for these pathogens to confirm diagnosis and determine antibiotic susceptibility. Empiric treatment with a quinolone or azithromycin is reasonable after a specimen has been taken. Patients with subacute, nonbloody diarrhea more typically have parasitic infections with organisms like Giardia lamblia or Cryptosporidium sp. These can be diagnosed with stool antigen detection assays or microscopic examination for ova and parasites. In the case of Cryptosporidium sp., laboratories will need to utilize special stains to visualize the organism, and the clinician should alert the laboratory that this diagnosis is being considered. Some travelers with persistent symptoms despite negative stool studies have developed a postinfectious irritable bowel syndrome rather than active, ongoing infection.
FEVER IN THE RETURNING TRAVELER
The first priority in a returning traveler with fever is evaluation for malaria. A delay in the diagnosis or treatment of malaria can lead to substantial morbidity and death. Returning travelers with fever should have thin and thick blood smears sent to assess for malaria. Antigen detection assays can supplement visual examination. A diagnosis of malaria should prompt rapid consultation with an infectious disease expert or a malaria clinician at the Centers for Disease Control and Prevention (Malaria Hotline in the United States: 770-488-7788 or 770-488-7100 after working hours, weekends, or holidays).
Other causes of fever in returning travelers include enteric fever caused by Salmonella typhi or paratyphi, dengue, viral hepatitis, acute HIV, leptospirosis, schistosomiasis, tick bite fever, and tuberculosis (table 9.2). Dengue is becoming increasingly prevalent.
Table 9.2 SOURCES OF FEVER IN THE RETURNING TRAVELER
| Malaria | 35% |
| Viral hepatitis | 5% |
| Respiratory tract infections | 5% |
| Dysentery | 5% |
| Dengue fever | 5% |
| Urinary tract infections | 3% |
| Typhoid fever | 2% |
| Tuberculosis | 1% |
| Rickettsial infection | 1% |
| Acute HIV infection | 1% |
| Amebic liver abscess | 0.5% |
LYME DISEASE
EPIDEMIOLOGY
Lyme disease is the most common tick-borne illness in the United States and Europe. The causative pathogen is the spirochete Borrelia burgdorferi. Borrelia is transmitted to humans by the deer tick Ixodes scapularis or Ixodes pacificus. Lyme disease is found throughout the United States but it is most commonly reported in the US northeast and in northwest California. Most cases occur during the summer months, but cases can present year round. People with dogs and those living in or visiting wooded areas are at greatest risk.
CLINICAL PRESENTATION
The clinical presentation of Lyme occurs in three stages (table 9.3). The disease begins at the site of a tick bite with an erythema migrans rash (Figure 9.2). In order for disease transmission to occur, an infected tick must feed on its human host for at least 36 hours. Nonetheless, many patients do not recall the precipitating tick bite. The appearance of an erythema migrans rash is diagnostic of Lyme disease. Patients with an erythema migrans rash ought to be treated without further investigation because up to 60% of patients with primary disease will have negative Lyme enzyme-linked immunosorbent assays (ELISA). Since ticks often bite in areas that are not easily visualized (such as in the gluteal folds or back of the neck), patients may not be aware that they have erythema migrans and therefore do not present for medical care.
Table 9.3 LYME DISEASE—STAGES, PRESENTATION, TREATMENTS
NOTE: * Alternatives: amoxicillin 500 mg orally three times daily or cefuroxime 500 mg orally twice daily.
Figure 9.2. Erythema migrans rash of early Lyme disease.
Within days to weeks of inoculation, the Borrelia spirochetes disseminate through the body. Patients at this second stage of infection can present with multiple erythema migrans rashes spread over the body and with systemic symptoms such as fever, chills, headache, myalgias, and fatigue (Figure 9.3). A small subset of patients go on to develop transient focal disease in just about any organ of the body including meningitis, facial palsy, neuritis, conjunctivitis, atrioventricular heart block, myocarditis, migratory joint pains, and mild hepatitis. Patients at this stage of infection typically have positive Lyme ELISA tests.
Figure 9.3. Disseminated Lyme disease.
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