1000-2000 5 ьшò

suppository), intravaginally QHS for 7 days

–Clotrimazole (Gyne-Lotrimin, Mycelex): intravaginal suppository (100 mg QHS for 7 days; 200 mg QHS for 3 days; 500 mg daily for 1 day) or 2% cream (one applicator QHS for 3 days)

–Fluconazole 150 mg PO single dose

Oropharyngeal

–Mild disease

Clotrimazole (Mycelex): oral 10-mg troche; 20 minutes 5 times daily for 7 to 14 days

Nystatin suspension: 100,000 U/mLswish and swallow 400,000 to 600,000 U 4 times per day

Nystatin pastilles: 200,000 U each, QID daily for 7 to 14 days (4)[A]

Denture wearers

■Nystatin ointment: 100,000 U/g under denture and corners of mouth for 3 weeks

■Remove dentures at night; clean 2× weekly with diluted (1:20) bleach.

–Moderate to severe disease

Fluconazole: 200 mg load and then 100 to 200 mg (>14 days of age: 6

mg/kg × 1 dose and then 3 mg/kg q24h × 7 to 14 days [max 100 mg/day]) Esophagitis

–Fluconazole: PO 400 mg load and then 200 to 400 mg/day for 14 to 21 days or IV 400 mg (6 mg/kg) daily if oral therapy not tolerated

Pregnancy Considerations

2% miconazole cream, intravaginally, for 7 days in uncomplicated candidiasis; systemic amphotericin B for invasive candidiasis in pregnancy

Second Line

Vaginal

–Terconazole (Terazol): 0.4% cream (one applicator QHS for 7 days of induction therapy); 0.8% cream/80-mg suppositories (one applicator or one suppository QHS for 3 days)

–For recurrent cases (≥4 symptomatic episodes in 1 year): induction therapy with 10 to 14 days of topical or oral azole and then fluconazole 150 mg once per week for 6 months (4)[A]

In HIV patients: Concerns with this regimen include emergence of drug resistance (5)[A].

Oropharyngeal

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–Miconazole oral gel (20 mg/mL): QID, swish and swallow.

–Itraconazole (Sporanox) suspension: 200 mg (20 mL) daily; swish-swallow for 7 to 14 days.

–Posaconazole (Noxafil) oral suspension: 400 mg BID for 3 days and then 400 mg daily for up to 28 days

–Amphotericin B (Fungizone) oral suspension (100 mg/mL): 1 mLQID

daily, swish and swallow; use between meals. Esophagitis

–Amphotericin B (variable dosing) IV dose of 0.3 to 0.7 mg/kg daily or an echinocandin should be used for patients who cannot tolerate oral therapy.

–For refractory disease:

Itraconazole (Sporanox) oral solution: 200 mg daily

Posaconazole (Noxafil) oral suspension: 400 mg BID

Voriconazole (Vfend) 100 to 200 mg q12h PO or IV for 14 to 21 days (4) [A]

Continue treatments for 2 days after infection gone:

–Contraindications

Ketoconazole, itraconazole, or nystatin (if swallowed): severe hepatotoxicity

Amphotericin B: can cause nephrotoxicity

–Precautions

Miconazole: can potentiate the effect of warfarin but drug of choice in pregnancy

Fluconazole: renal excretion: rare; hepatotoxicity: resistance frequent

Itraconazole: Doubling the dosage results in ~3-fold increase in itraconazole plasma concentrations.

Possible interactions (rarely seen with creams, lotions, or suppositories)

–Fluconazole

Rifampin: decreased fluconazole concentrations

Tolbutamide: decreased concentrations

Warfarin, phenytoin, cyclosporine: altered metabolism; check levels.

–Itraconazole: potent CYP3A4 inhibitor. Carefully assess all coadministered medications.

–Work in progress for a vaccine in patients with chronic mucocutaneous candidiasis (3)[A]

ISSUES FOR REFERRAL

Evaluate patients without obvious reasons for recurrent superficial candidal

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infections for immunodeficiency (5)[A].

GI candidiasis

ADDITIONALTHERAPIES

For infants with thrush: Boil pacifiers and bottle nipples; assess mother’s breasts/nipples for Candida infection.

For denture-related candidiasis: Disinfect dentures (using soak solution of benzoic acid, 0.12% chlorhexidine gluconate, 1:20 NaOCl or alkalize proteases) and treat orally.

COMPLEMENTARY& ALTERNATIVE MEDICINE

Probiotics: Lactobacillus and Bifidobacterium may inhibit Candida spp.

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

Proper oral hygiene. Protocols for brushing, denture care, and oral cavity moistening reduce oral candidiasis.

ONGOING CARE

FOLLOW-UPRECOMMENDATIONS

Patient Monitoring

Immunocompromised persons benefit from regular evaluation and screening.

DIET

Active-culture yogurt or other live lactobacillus may decrease colonization; indeterminate evidence

PATIENT EDUCATION

Advise patients at risk for recurrence about potential for overgrowth with antibacterial therapy.

“Azole” medications are pregnancy Category C.

Polyene medications are pregnancy Category B; however, only give orally when benefits outweigh risks.

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PROGNOSIS

Benign prognosis in immunocompetent patients

For immunosuppressed persons, Candida may become an AIDS-defining illness with significant morbidity.

COMPLICATIONS

In HIV patients, moderate immunosuppression (e.g., CD4 200 to 500 cells/mm3) may be associated with chronic candidiasis (5)[A]. With more severe immunosuppression (e.g., CD4 <100 cells/mm3), esophagitis or systemic infection are possible.

REFERENCES

1.Yang IA, Clarke MS, Sim EH, et al. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012; (7):CD002991.

2.Coronado-Castellote L, Jiménez-Soriano Y. Clinical and microbiological diagnosis of oral candidiasis. J Clin Exp Dent. 2013;5(5):e279–e286.

3.Hani U, Shivakumar HG, Vaghela R, et al. Candidiasis: a fungal infection— current challenges and progress in prevention and treatment. Infect Disord Drug Targets. 2015;15(1):42–52.

4.Martins N, Ferreira IC, Barros L, et al. Candidiasis: predisposing factors, prevention, diagnosis and alternative treatment. Mycopathologia. 2014;177(5–6):223–240.

5.Wang X, van der Veerdonk FL, Netea MG. Basic genetics and immunology of Candida infections. Infect Dis Clin North Am. 2016;30(1):85–102.

ADDITIONALREADING

Glenny AM, Gibson F, Auld E, et al. The development of evidence-based guidelines on mouth care for children, teenagers and young adults treated for cancer. Eur J Cancer. 2010;46(8):1399–1412.

Kumar S, Bansal A, Chakrabarti A, et al. Evaluation of efficacy of probiotics in prevention of candida colonization in a PICU—a randomized controlled trial. Crit Care Med. 2013;41(2):565–572.

Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for

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Disease Control and Prevention, the National Institutes of Health, and the HIV

Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed December 13, 2016.

SEE ALSO

Candidiasis, Invasive; HIV/AIDS

CODES

ICD10

B37.9 Candidiasis, unspecified

B37.0 Candidal stomatitis

B37.49 Other urogenital candidiasis

CLINICALPEARLS

Candidiasis is generally a clinical diagnosis. KOH preparations are a simple confirmatory office test. Culture and biopsy are rarely needed.

Person-to-person transmission is rare.

If tongue pain continues after treatment, consider burning mouth syndrome. Obtain a biopsy if there is concern for oral cancer.

Oral antifungal medications are hepatically metabolized and may have serious side effects.

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CARBON MONOXIDE POISONING

Viren Kaul, MD Ahmed Agameya, MBBCh Anthony W.

Gray Jr., MD, FCCP, FCCM

BASICS

DESCRIPTION

Carbon monoxide (CO) is an odorless, tasteless, colorless gas that has the potential to cause sudden illness and death if inhaled.

CO is produced by combustion of carbon-containing compounds (wood, charcoal, oil, gas):

–CO inhalation leads to displacement of oxygen from binding sites on hemoglobin.

–Detrimental effects are related to tissue hypoxia from decreased oxygen content and a (left) shift of the oxyhemoglobin dissociation curve that

impairs oxygen unloading from hemoglobin.

CO binds to mitochondrial cytochrome oxidase, impairing adenosine triphosphate (ATP) production. It also binds to myoglobin, affecting muscle function.

System(s) affected: cardiovascular, pulmonary, musculoskeletal, nervous

Pregnancy Considerations

Tissue hypoxia due to CO poisoning may cause significant fetal abnormalities. CO has a greater affinity for (and longer half-life bound to) fetal hemoglobin. A pregnant mother may be unaffected, whereas the fetus is adversely impacted.

EPIDEMIOLOGY

Incidence

Third leading cause of unintentional poisoning deaths in the United States with an average 438 deaths annually

~50,000 emergency department visits annually

Unintentional poisoning is most common during winter months in cold climates.

Intentional CO poisoning ~10 times higher than unintentional poisonings Likely underdiagnosed because some patients may not seek medical attention

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due to vague symptoms

ETIOLOGYAND PATHOPHYSIOLOGY

CO is rapidly absorbed in lungs.

CO has ~240 times the affinity for hemoglobin compared to oxygen.

CO binds to hemoglobin to form carboxyhemoglobin (COHb), resulting in impaired oxygen-carrying capacity, utilization, and delivery:

–CO interferes with peripheral oxygen utilization by inactivating cytochrome oxidase.

Delayed neurologic sequelae, related to lipid peroxidation by toxic oxygen species generated by xanthine oxidase

The half-life of CO on room air is ~320 minutes, whereas breathing 100% oxygen via a tight-fitting, nonrebreathing face mask decreases to ~74 minutes. With 100% hyperbaric oxygen, T1\2 is ~30 minutes (1).

CO can promote nitric oxide release causing profound hypotension.

CO affects L-type myocardial calcium channels causing myocardial depression.

Inhaled or ingested methylene chloride (from paint remover [dichloromethane]) is metabolized to CO by the liver, potentially resulting in acute CO toxicity.

RISK FACTORS

Alcohol use; smoking

Elderly and infants at higher risk if exposed

Closed or improperly ventilated space with faulty furnace, stove, engine, or other fuel-burning device

Cigarette smoking

Use of generators during power outages and storms

Underlying cardiovascular disease, anemia, chronic respiratory conditions

Exposure to exhaust (e.g., riding in the back of enclosed pickup trucks or swimming near a motor boat) in precatalytic converter era automobiles Employment in a coal mine, as an auto mechanic, paint stripper, or in the

solvent industry

Increased endogenous production in patients with hemolytic anemia

GENERALPREVENTION

Appropriate ventilation, especially around fuel-burning devices Use of CO monitors

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Determining the mechanism of exposure is critical in cases of accidental poisoning helps limit future risk.

Victims must not return to contaminated environment.

Regular building maintenance to ensure safe environment and adequate ventilation

Public policy to ensure building code safety

COMMONLYASSOCIATED CONDITIONS

CO and cyanide poisoning can occur simultaneously following smoke inhalation (synergistic effect).

Consider CO poisoning in a burn victim who has been in an enclosed space.

DIAGNOSIS

Acute CO poisoning: inhalation of air with high concentrations of CO, usually after a single occasion, leading to a spectrum of nonspecific symptoms ranging from headaches, nausea, malaise, and dizziness to seizures, syncope, coma, arrhythmias, myocardial ischemia, and profound lactic acidosis

Chronic CO poisoning: repeated exposure to low concentrations of CO

Older pulse oximeters do not differentiate COHb from oxyhemoglobin, causing normal pulse oximeter readings in hypoxic patients. Eight-wavelength CO-oximeters that can detect CO exposure are not yet routinely available for diagnostic purposes.

Level >3% in a nonsmoker and >10% in a smoker confirms exposure. The level does not correlate with the severity of the illness or long-term prognosis (1).

HISTORY

Duration and mechanism of exposure

Exclude pregnancy

Minor nonspecific symptoms

–Headaches: occurs in 84% patients

–Dizziness

–Nausea, vomiting, diarrhea

–Weakness or fatigue

Major symptoms

–Confusion or impaired judgment

–Seizures

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–Chest pain

–Shortness of breath

–Loss of consciousness

–Visual disturbances

PHYSICALEXAM

Patients usually present with confusion or altered mental status.

Examine for signs of burns (enclosed space fires) or other secondary injuries.

“Cherry red” appearance of the lips and skin (<1% cases)

Respiratory depression or tachypnea

Cyanosis

Visual-field defects, papilledema, or nystagmus

CNS depression or coma, ataxia, seizure

Tachycardia, hypotension, cardiac dysrhythmias, or even (cardiac) arrest

Mental status examination

DIFFERENTIALDIAGNOSIS

Cyanide toxicity

Methylene chloride (dichloromethane) inhalation or ingestion

Viral syndromes

Psychological disorders including major depressive disorder Other causes of mental status changes:

–Infections such as meningitis or encephalitis

–Metabolic causes such as hypoglycemia

–Drugs: alcohol (EtOH) intoxication, opiates, acetylsalicylic acid (ASA) overdose

–Trauma

–CNS lesions

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

Measurement of COHb (may be low despite significant poisoning if patient had been treated with O2 or if significant time elapses before the level is

drawn)

ABG (metabolic acidosis)

–Blood PO2 (PaO2) tends to be normal as O2 dissolved in blood is not affected by CO.

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Anion gap = ([Na+] + [K+]) − ([Cl−] + [HCO3−]); >16

Pregnancy test in all women of childbearing age

Toxicology screen

Serum chemistries

ECG in all patients

Hemoglobin/hematocrit

CK to evaluate rhabdomyolysis

Consider cardiac enzymes if:

–≥65 years

–Patient with cardiac risk factors or anemia

–Symptoms suggestive of cardiac ischemia

Head CT/MRI scan can help rule out other causes of neurologic decompensation; may also show infarction due to hypoxia/ischemia

Follow-Up Tests & Special Considerations

Consider CO poisoning in younger patients with chest pain or symptoms suggestive of ischemia.

Consider the diagnosis and explore potential exposure in afebrile patients with “flulike” symptoms, (especially in the winter when influenza and CO poisoning are both more common).

Look for clusters of patients (coworkers, family members, school children) with similar symptoms.

Patients with intentional poisoning require behavioral evaluation when medically stable.

Implement acute suicide precautions if appropriate.

TREATMENT

GENERALMEASURES

Prompt removal from the CO source

Supportive care as necessary

Intubation and mechanical ventilation may be necessary for severe intoxication, if patient is not able to protect airway, or if patient has significant respiratory depression.

Poison Control: 800-222-1222 (United States only)

MEDICATION

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