TABLE IV-114 Risk Factors for Active Tuberculosis Among Persons Who Have Been Infected With Tubercle Bacilli 5 page
IV-197. The answer is D. (Chap. 203) Reviews of cases reveal consistent conditions and risk factors associated with hematogenous dissemination of Candida. Many refer to the fact that innate immunity is the most important defense mechanism against hematogenous dissemination of the fungus and that neutrophils are the most important component of this defense. Many immunocompetent people have antibodies to Candida spp.; the role of these antibodies in the defense against hematogenous spread is not clear. Therefore, patients the conditions and risk factors listed in the question plus indwelling urinary catheters, parenteral glucocorticoids, neutropenia, cytotoxic chemotherapy, and immunosuppressive agents for organ transplantation all confer risk of disseminated candidiasis. Additionally, low birth weight infants, HIV-infected patients with low CD4 counts, and patients with diabetes are at great risk of local infection with Candida that may disseminate when other predisposing factors are present (e.g., catheters). Women receiving antibiotics are at risk of developing vaginal candidiasis. Patients with pulmonary alveolar proteinosis are at risk of infection with unusual organisms such as Nocardia, atypical mycobacteria, Aspergillus, and pneumocystis but are not at increased risk of disseminated candidiasis in the absence of other risk factors.
IV-198. The answer is D. (Chaps. 198 and 203) This patient presents with the classic skin presentation of disseminated candidiasis. The skin lesions, severe myalgias, joint pains, and fever are typical manifestations of hematogenous spread from either a gastrointestinal or skin source in a patient predisposed by neutropenia and indwelling catheters. The severe myalgias are a characteristic of this syndrome and should be taken seriously as a new complaint in a susceptible host. Blood culture results are likely be positive, but staining of the skin lesions is positive in virtually 100% of cases. Candida is the only fungus that can typically be visualized on tissue Gram stain in the form of pseudohyphae and hyphae. Aspergillus is seen in tissue as clumps of branching (45 degrees) septated hyphae often with angioinvasion and necrosis. Aspergillus may also disseminate in a prolonged neutropenic patient, usually from a lung infection, and cause rapidly progressive skin lesions, usually with a necrotic center. Histoplasma and Blastomyces can be visualized in tissue as budding yeast. Encapsulated yeasts on India ink are indicative of Cryptococcus. Spherules are specific to coccidioidomycosis.
IV-199. The answer is D. (Chap. 203) Candida spp. are susceptible to a number of systemic antifungal agents. Most institutions chose an agent based on their local epidemiology and resistance patterns. Fluconazole is the most commonly used agent for nonneutropenic hemodynamically stable patients unless azole resistance is considered an issue. In a hemodynamically unstable neutropenic patient, more broad-spectrum agents are typically used such as polyenes, echinocandins, or later-generation azoles such as voriconazole. (See Table IV-199 .) Lipid formulations of amphotericin, although not approved by the U.S. Food and Drug Administration as primary therapy, are commonly used because they are less toxic than amphotericin B deoxycholate. At present, the vast majority of isolates of Candida albicans are sensitive to fluconazole. Candida glabrata and Candida krusei are more sensitive to polyenes and echinocandins. Flucytosine is not used as sole therapy for Candida. It may be combined with amphotericin for treatment of Candida endophthalmitis and meningitis.
TABLE IV-199 Agents for the Treatment of Disseminated Candidiasis
IV-200. The answer is B. (Chap. 203) The use of antifungal agents to prevent Candida infections remains controversial, but some general principles have emerged in recent years. Most centers start prophylactic fluconazole to allogeneic stem cell transplant recipients. Many centers also administer them to high-risk liver transplant recipients but not routine living related renal transplant recipients. This prophylaxis should be differentiated from the administration of empiric broad-spectrum antifungal therapy in a patient with prolonged febrile neutropenia. Voriconazole is an appropriate choice for empiric broad-spectrum therapy in an unstable patient with suspected candidemia, but it has not been shown to be superior to any other agent for prophylaxis against Candida in any population. Complicated postoperative surgical patients are at risk of Candida infection, and some centers administer prophylaxis to very high-risk patients. However, the widespread use of Candida prophylaxis in surgical patients is not recommended because the incidence of disseminated candidiasis is low, the cost-benefit ratio is suboptimal, and there is reasonable rationale to believe that this strategy
could increase Candida resistance to current medications. Candida prophylaxis for HIV-infected patients is recommended to prevent frequent recurrent oropharyngeal or esophageal infection.
IV-201. The answer is C. (Chap. 203) Isolation of yeast from the bloodstream can virtually never be considered a contaminant. Presentation may be indolent with malaise only or fulminant with overwhelming sepsis in the neutropenic host. All indwelling catheters need to be removed to ensure clearance of infection, and evaluation for endocarditis and endophthalmitis should be strongly considered, particularly in patients with persistently positive cultures or fever. Both of these complications of fungemia often entail surgical intervention for cure. A positive yeast culture in the urine is often difficult to interpret, particularly in patients taking antibiotics and in the intensive care unit. Most frequently, a positive culture result for yeast represents contamination even if the urinalysis suggests bladder inflammation. An attractive option is to remove the Foley catheter and recheck a culture. Antifungals are indicated if the patient appears ill, in the context of renal transplant in which fungal balls can develop in the graft, and often in neutropenic patients. Candida pneumonia is uncommon even in immunocompromised patients. A positive yeast culture of the sputum is usually representative of commensal oral flora and should not be managed as an infection, particularly as in this patient in whom acute bacterial pneumonia is likely.
IV-202. The answer is C. (Chap. 203) Candidemia may lead to seeding of other organs. Among nonneutropenic patients, up to 10% develop retinal lesions; therefore, it is very important to perform thorough funduscopy. Focal seeding can occur within 2 weeks of the onset of candidemia and may occur even if the patient is afebrile or the infection clears. The lesions may be unilateral or bilateral and are typically small white retinal exudates. However, retinal infection may progress to retinal detachment, vitreous abscess, or extension into the anterior chamber of the eye. Patients may be asymptomatic initially but may also report blurring, ocular pain, or scotoma. Abdominal abscess are possible but usually occur in patients recovering from profound neutropenia. Fungal endocarditis is also possible but is more common in patients who use intravenous drugs and may have a murmur on cardiac examination. Fungal pneumonia and pulmonary abscesses are very rare and are not likely in this patient.
IV-203. The answer is A. (Chap. 204) Aspergillus has a worldwide distribution, typically growing in decomposing plant materials. Immunocompetent individuals generally do not develop disease without intense exposure such as during construction or handling of moldy hay, bark, or compost. Nosocomial outbreaks are usually directly related to contaminated air source in the hospital. HEPA filtration is effective in eliminating infection from operating rooms and units with high-risk patients. Contaminated water sources are the typical reservoir of nosocomial Legionella outbreaks. Patient-to-patient spread in waiting rooms has been described for cystic fibrosis patients transmitting Burkholderia infection. Provider-to-patient transmission of methicillin-resistant Staphylococcus aureus and most other bacteria is reduced with effective use of alcohol-based disinfectant; however, in the case of Clostridium difficile, alcohol will not eliminate spores, and effective handwashing with soap and water is necessary.
IV-204. The answer is B. (Chap. 204) Diagnosis of invasive Aspergillus infection is often difficult because early therapy is essential, and approximately 40% of cases are missed clinically and are diagnosed at autopsy. Sputum culture is positive in only 10% to 30% of patients; the yield is higher when fungal media rather than bacterial agar is used. Thus, specifically requesting fungal culture is necessary. The Aspergillus antigen assay relies on galactomannan release during fungal growth. Antigen
testing results are positive days before clinical or radiologic abnormalities appear. The test may be falsely positive in patients receiving β-lactam/β-lactamase inhibitor antibiotics. The sensitivity in patients with prolonged neutropenia is likely about 80%. Prior therapeutic or empiric use of antifungal therapy lowers the sensitivity of the serum test. The test can be performed on bronchoalveolar lavage samples. The computed tomography findings in this case are also typical of the “halo sign” often seen in cases of invasive pulmonary aspergillosis. The halo of ground glass infiltrate surrounding an Aspergillus nodule represents hemorrhagic infarction. Other fungi may cause the halo sign, but Aspergillus, because of the tendency to be angioinvasive, is the most common. The other diagnoses in this case are much less likely given the clinical history and the radiologic signs.
IV-205. The answer is E. (Chap. 204) Intravenous voriconazole is currently the preferred therapy for invasive aspergillosis. Caspofungin, posaconazole, and lipid-based formulations of amphotericin are second-line agents. Amphotericin is not active against Aspergillus terreus or Aspergillus nidulans. Fluconazole is active against Candida spp. but not Aspergillus spp. Trimethoprim–sulfamethoxazole is used for therapy against Pneumocystis jiroveci.
IV-206. The answer is A. (Chap. 204) Aspergillus infection has many clinical manifestations. Invasive aspergillosis typically occurs in immunocompromised patients and presents as rapidly progressive pulmonary infiltrates. Infection progresses by direct extension across tissue planes. Cavitation may occur. Allergic bronchopulmonary aspergillosis (ABPA) is a different clinical entity. It often occurs in patients with preexisting asthma or cystic fibrosis. It is characterized by an allergic reaction to Aspergillus spp. Clinically, it is characterized by intermittent wheezing, bilateral pulmonary infiltrates, brownish sputum, and peripheral eosinophilia. Immunoglobulin E may be elevated, suggesting an allergic process, and a specific reaction to Aspergillus spp. that is manifested by serum antibodies or skin testing is common. Although central bronchiectasis and fleeting infiltrates caused by mucus plugging are common radiographic findings in ABPA, the presence of peripheral cavitary lung lesions is not a common feature.
IV-207. The answer is E. (Chap. 204) Allergic bronchopulmonary aspergillosis (ABPA) is not a true infection but rather a hypersensitivity immune response to colonizing Aspergillus spp. It occurs in about 1% of patients with asthma and in up to 15% of patients with cystic fibrosis. Patients typically have wheezing that is difficult to control with usual agents, infiltrates on chest radiographs caused by mucus plugging of airways, a productive cough often with mucus casts, and bronchiectasis. Eosinophilia is common if glucocorticoids have not been administered. The total immunoglobulin E (IgE) is of value if greater than 1000 IU/mL in that it represents a significant allergic response and is very suggestive of ABPA. In the proper clinical context, a positive skin test result for Aspergillus antigen or detection of serum Aspergillus-specific IgG or IgE precipitating antibodies are supportive of the diagnosis. Galactomannan enzyme immunoassay is useful for invasive aspergillosis but has not been validated for ABPA. There is no need to try to culture an organism via bronchoalveolar lavage to make the diagnosis of ABPA. Chest computed tomography, which may reveal bronchiectasis, or pulmonary function testing, which will reveal an obstructive defect, will not be diagnostic.
IV-208. The answer is B. (Chap. 204) The primary risk factor for developing invasive Aspergillus infection is neutropenia and glucocorticoid use (Figure IV-208). Risk is proportional to the degree and length of neutropenia and the dose of glucocorticoid. Stable HIV patients rarely develop invasive
aspergillosis. Patients with AIDS are at some risk, typically in the context of prolonged neutropenia or advanced disease. Patients with graft-versus-host disease and uncontrolled leukemia are at particularly elevated risk. The infection is seen in solid organ transplant patients, particularly those requiring high cumulative doses of glucocorticoids for graft rejection. Recent reports describe an increasing incidence of invasive Aspergillus infection in medical intensive care units, particularly in patients with preexisiting lung disease such as pneumonia or chronic obstructive pulmonary disease. Glucocorticoid use does not appear to increase the risk of invasive sinus disease, only lung infection. Anti–tumor necrosis factor therapy also increases the risk of invasive Aspergillus infection.
25-
?20-
FIGURE IV-208
Degree of :ninjntranpromi$6
IV-209. The answer is B. (Chap. 205) Mucormycosis refers to life-threatening infection caused by the Mucorales (formerly known as Zygomycetes) family of fungi. The most common fungus accounting for these infections is Rhizopus oryzae. The mortality rate of these infections approaches 50%. The Mucorales are environmentally ubiquitous; infection requires a defect in the patient’s ability to killing or phagocytic function. The most common predisposing factors are diabetes, glucocorticoid therapy, neutropenia, and iron overload. Free iron supports fungal growth in serum and tissues, enhancing survival and virulence. Deferoxamine therapy predisposes to fatal infection because the chelator acts as a siderophore, directly delivering iron to the fungi. Acidosis also causes dissociation of iron from serum proteins, promoting growth of Mucorales. Patients with diabetic ketoacidosis are at particularly high risk of developing rhinocerebral mucormycosis likely because of the combination of acidosis and phagocytic defects associated with hyperglycemia. Hypoglycemia is not an identified risk factor for mucormycosis.
IV-210. The answer is E. (Chap. 205) This patient has evidence of invasive rhinocerebral mucormycosis with risk factors including acute and chronic hyperglycemia and metabolic acidosis caused by chronic renal insufficiency. With a greater than 50% mortality rate, therapy of rhinocerebral mucormycosis requires early diagnosis, reversal of underlying predisposing conditions, surgical debridement, and immediate antifungal therapy. Insulin and hemodialysis should be initiated to correct hyperglycemia and metabolic acidosis. Amphotericin products remain the treatment of choice for mucormycosis. Liposomal amphotericin has improved central nervous system penetration compared with the lipid complex formations. Surgical debridement is also an important component of early therapy. If untreated, the infection quickly spreads from the ethmoid sinus to the orbit and into the cavernous sinus. Development of contralateral signs suggests cavernous sinus thrombosis and portends a very poor prognosis. Differentiation of mucormycosis from Aspergillus is important because they tend to infect similar hosts and are rapidly fatal. In contrast to mucormycosis species, the hyphae of Aspergillus spp. are septated, are thinner, and branch at acute angles. Voriconazole, the initial therapy for Aspergillus infection, is not indicated in mucormycosis and in fact has been shown to exacerbate mucormycosis in animal models. Echinocandin antifungal agents have activity against Mucorales, and animal data suggest that they may have a role in combination with lipid polyene agents.
IV-211. The answer is E. (Chap. 205) The sites of infection due to Mucorales fungal infection tend to affect patients with specific host defense defects. The most common clinical manifestation of mucormycosis is rhinocerebral. Most cases occur in patients with diabetes or hyperglycemia caused by glucocorticoid therapy (e.g., solid organ transplantation). The initial symptoms usually include facial or orbital pain or numbness, facial suffusion, and soft tissue swelling. The infection usually originates in the ethmoid sinus region and spreads rapidly to the orbit and central nervous system. Painful necrotic lesions may be seen in the mouth. Pulmonary mucormycosis is the second most common manifestation of Mucorales infection. Human stem cell transplantation is a common risk factor for pulmonary mucormycosis. The risk factors and presentation are similar to that of invasive pulmonary Aspergillus infection. Differentiation is important because antifungal therapy differs. The two diseases appear similar on chest computed tomography, although the presence of more than 10 nodules, pleural effusion, or concomitant sinusitis makes mucormycosis more likely. Other sites of involvement with mucormycosis are described but less common. Cutaneous disease may result from external implantation
(soil-related trauma or plant penetration) or hematogenous dissemination. Implanted cutaneous disease is also highly invasive; the development of fasciitis has a greater than 70% mortality rate. Rapid surgical debridement is essential. Hematogenous dissemination has a very high mortality rate; involvement of the brain has a near 100% mortality rate. Gastrointestinal mucormycosis is most common in neonates with necrotizing enterocolitis.
IV-212. The answer is E. (Chap. 206) This patient has tinea capitis most likely caused by the dermatophytic mold, Trichophyton spp. The other dermatophytes that less frequently cause cutaneous infection include Microsporum and Epidermophyton spp. They are not part of the normal skin flora but can live in keratinized skin structures. Infections with these organisms are extremely common and are often called ringworm, although the causative organisms are fungi, not worms. They manifest as infection of the head (tinea capitis), feet (tinea pedis), crotch (tinea cruris), and nails (tinea unguium or onychomycosis). Tinea capitis is most common in children ages 3 to 7 years but also occurs in adults. Usually, the typical appearance, as in this case, is diagnostic. Scrapings may be taken from the edge of lesion and stained with KOH to reveal hyphae. Dermatophyte infections often respond to topical therapy. For troublesome infections, itraconazole or terbinafine for 1 to 2 weeks can hasten resolution. Terbinafine is often preferred because of fewer drug interactions.
IV-213. The answer is D. (Chap. 206) Sporothrix schenckii is a thermally dimorphic fungus found in soil, plants, and moss and occurs most commonly in gardeners, farmers, florists, and forestry workers. Sporotrichosis develops after inoculation of the organism into the skin with a contaminated puncture or scratch. The disease typically presents as a fixed cutaneous lesion or with lymphocutaneous spread. The initial lesion typically ulcerates and become verrucous in appearance. The draining lymphatic channels become affected in up to 80% of cases. This presents as painless nodules along the lymphatic channel, which ulcerate. A definitive diagnosis is made by culturing the organism. A biopsy of the lesion may show ovoid or cigar-shaped yeast forms. Treatment for sporotrichosis is systemic therapy. Options include oral itraconazole, saturated solution of potassium iodide, and terbinafine. However, terbinafine has not been approved for this indication in the United States. Topical antifungals are not effective. In cases of serious system disease such as pulmonary sporotrichosis, amphotericin B is the treatment of choice. Caspofungin is not effective against S. schenckii.
IV-214. The answer is C. (Chap. 207) Patients receiving biologic agents, including the tumor necrosis factor antagonists infliximab and etanercept, are at increased risk of multiple infections, including pneumocystis. Pneumocystis is thought to be a worldwide organism with most people exposed before 5 years of age. Airborne transmission has been demonstrated in animal studies, and epidemiologic studies suggest person-person transmission in nosocomial settings. Patients with defects in cell and humoral immunity are at risk for developing pneumonia. Most cases are in HIV-infected patients with CD4 counts less than 200/μL. Others at risk include patients receiving immunosuppressive agents (particularly glucocorticoids) for cancer or organ transplantation, children with immunodeficiency, premature malnourished infants, and patients receiving biologic immunomodulating agents. Pneumocystis pneumonia typically presents in non–HIV-infected patients with several days of dyspnea, fever, and nonproductive cough. Often symptoms develop during or soon after a glucocorticoid taper. Pneumocystis is associated with a reduced diffusing capacity on pulmonary function that typically causes mild hypoxemia and significant oxygen desaturation with exertion. Chest radiography often shows bilateral diffuse infiltrates without pleural effusion. Early in the disease, the radiograph may be
unremarkable, but chest computed tomography (CT) will show diffuse ground glass infiltrates as in this case. Patients receiving biologic agents are at risk of pneumonia caused by tuberculosis (the patient was on prophylaxis in this case), Aspergillus spp., and Nocardia spp. Aspergillus spp., Nocardia spp., and septic emboli typically appears as nodules on chest CT. Rheumatoid nodules would be unlikely in the context of improving joint disease.
IV-215. The answer is D. (Chap. 207) Prophylaxis is effective in decreasing the risk of Pneumocystis pneumonia. It is clearly indicated in HIV-infected patients with oropharyngeal candidiasis or CD4 count below 200/μL and in HIV-infected or non–HIV-infected patients with a history of prior Pneumocystis pneumonia. Prophylaxis may be discontinued in HIV-infected patients who respond to therapy after the CD4 count has risen more than 200/μL for more than 3 months. Indications for primary prophylaxis for at-risk non-HIV infected patients without prior pneumocystis pneumonia (e.g., patients receiving induction chemotherapy or high-dose corticosteroids) are less clear. Trimethoprim– sulfamethoxazole remains the drug of choice for primary and secondary prophylaxis. It also provides protection from opportunistic toxoplasmosis and some bacterial infections.
IV-216. The answer is E. (Chap. 207) Pneumocystis jiroveci lung infection is known to worsen after initiation of treatment, likely caused by lysis of organisms and immune response to their intracellular contents. It is thought that adjunct administration of glucocorticoids may reduce inflammation and subsequent lung injury in patients with moderate to severe pneumonia caused by P. jiroveci . Adjunct administration of glucocorticoids in patients with moderate to severe disease as determined by a room air below 70 mmHg or an A–a gradient greater than 35 mmHg has been shown to decrease mortality. Glucocorticoids should be given for a total duration of 3 weeks. Patients often do not improve until many days into therapy and often initially worsen; steroids should be used early in the course of illness rather than waiting for lack of improvement. Pneumothoraces and adult respiratory distress syndrome (ARDS) are common feared complications of Pneumocystis infection. If patients present with ARDS caused by Pneumocystis pneumonia, they meet the criterion for adjunct glucocorticoids because of the severe nature of disease. The use of glucocorticoids as adjunctive therapy in HIV-infected patients with mild disease or in non–HIV-infected patients remains to be evaluated.
IV-217. The answer is A. (Chap. 208) Mefloquine remains the preferred drug for malaria prophylaxis in areas where chloroquine resistance is prevalent. High doses may be used for treatment. Drug resistance has been reported in parts of Africa and Southeast Asia. Mefloquine, similar to quinine and chloroquine, is only active against the asexual erythrocytic stages of malarial infection. Mefloquine is poorly water soluble and is not available parenterally. Oral absorption is enhanced when taken with or after food. Mefloquine is excreted mainly in bile and feces. Dosage adjustment is not necessary in patients with renal failure, and the drug is not removed with hemodialysis. Sleep abnormalities, psychosis, and seizures have been reported with mefloquine administration. Mefloquine should not be prescribed to patients with neuropsychiatric conditions, including depression, generalized anxiety disorder, psychosis, or seizure disorders. If acute anxiety, depression, restlessness, or confusion develops during prophylaxis, the drug should be discontinued. Quinine, quinidine, and beta-blockers may interact with mefloquine to cause significant electrocardiographic abnormalities or cardiac arrest. Halofantrine must not be administered with mefloquine within 3 weeks because of the potential for fatal QTc prolongation. Mefloquine may also alter ritonavir pharmacokinetics.
IV-218. The answer is E. (Chap. 209) Entamoeba histolytica is a common pathogen in areas of the
world with poor sanitation and crowding. Transmission is oral–fecal, and the primary manifestation is colitis, often heme positive. Liver abscess is a common complication, occurring after the organism crosses the colonic border and travels through the portal circulation, subsequently lodging in the liver. At the time of presentation with liver abscess, the primary gastrointestinal infection has usually cleared, and organisms cannot be identified in the stool. Suggestive imaging with a positive serologic test result for E. histolytica is diagnostic. When a patient has a diagnostic imaging procedure, a positive amebic serology result is highly sensitive (>94%) and highly specific (>95%) for diagnosis of amebic liver abscess. Treatment for amebic liver abscess is generally with metronidazole. Luminal infection can be treated with paromomycin or iodoquinol. Campylobacter is a major cause of foodborne infectious diarrhea. Although usually self-limited, it may cause serious enteritis and inflammatory diarrhea but not liver abscess.
IV-219. The answer is B. (Chap. 210) The patient presents with signs of an acute infectious illness in an endemic area for malaria. A thick and thin preparation of her peripheral blood is indicated to evaluate for trophozoites, and indeed they are found in this case. Her neurologic findings suggest cerebral malaria, a defining feature of severe malaria. She is treated with intravenous quinidine. Hypoglycemia is a frequent finding in severe malaria; is associated with a poor prognosis; and may be worsened by quinidine or quinine therapy, which promotes pancreatic insulin secretion. Quinine causes fewer arrhythmias and hypotension with infusion than quinidine, but it is often not available in U.S. hospital pharmacies. Malaria itself causes hypoglycemia through failure of hepatic gluconeogenesis as well as increased glucose consumption by the host and parasite. Seizures may be caused by cerebral malaria but are not a complication of quinidine. Nightmares are frequently found with mefloquine, and retinopathy is a complication of prolonged chloroquine dosing.
IV-220. The answer is C. (Chap. 210) Severe malaria is a medical emergency. The patient has infection with Plasmodium vivax, which is less likely than Plasmodium falciparum to be associated with severe disease. Clinical manifestations of severe disease that cannot be managed as an outpatient include the presence of coma or cerebral malaria, two or more seizures over 24 hours, severe academia or anemia, renal failure, pulmonary edema or adult respiratory distress syndrome, hypoglycemia, hypotension or shock, evidence of disseminated intravascular coagulation, hemoglobinuria, extreme weakness, and jaundice with bilirubin above 3 mg/dL if combined with other organ dysfunction. Finally, if more than 5% of the erythrocytes are affected on the peripheral smear in a non-immune patient, severe malaria is present, and outpatient therapy is not advised.
IV-221. The answer is B. (Chap. 210) Artemisinin-containing regimens are now recommended by the World Health Organization as first-line agents for Plasmodium falciparum malaria. In severe P. falciparum malaria, intravenous (IV) artesunate reduced mortality by 35% compared with IV quinine. Artemether and artemotil are given intramuscularly and are not as effective as artesunate. Although safer and more effective than quinine, artesunate is not available in the United States. In the United States, quinidine or quinine is used as a necessary choice. Intravenous quinine is as effective as and safer than IV quinidine. Quinine causes fewer arrhythmias and hypotension with infusion than quinidine, but it is often not available in U.S. hospital pharmacies. Chloroquine is only effective for Plasmodium vivax and in Plasmodium ovale and Plasmodium falciparum infection in certain pockets of the Middle East and Caribbean where resistance has not yet developed. Mefloquine comes only as an oral formulation. It is most commonly used as a prophylactic agent but is also used for treatment of