Co-trimoxazole and Norepinephrine Bitartrate

• Generic Name: sulfamethoxazole / trimethoprim
• Dosage Forms: n.a.
• Other Brand Names: Bactrim, Bactrim DS, Septra, Septra DS, Sulfatrim, Bactrim IV, Septra IV, SMZ-TMP DS, Sulfatrim Pediatric, Bethaprim, Cotrim, Uroplus, Uroplus DS, Cotrim DS, Bactrim Pediatric, Bethaprim Pediatric, Sulfatrim Suspension, Cotrim Pediatric

Treatment of acute otitis media (AOM) in adults and children caused by susceptible Streptococcus pneumoniae or Haemophilus influenzae when the clinician makes the judgment that the drug offers some advantage over use of a single anti-infective.

Not a drug of first choice; considered an alternative for treatment of AOM, especially for those with type I penicillin hypersensitivity. Because amoxicillin-resistant S. pneumoniae frequently are resistant to co-trimoxazole, the drug may not be effective in patients with AOM who fail to respond to amoxicillin.

Data are limited regarding safety of repeated use of co-trimoxazole in pediatric patients <2 years of age; the drug should not be administered prophylactically or for prolonged periods for treatment of AOM in any age group.

GI Infections

Treatment of travelers’ diarrhea caused by susceptible enterotoxigenic Escherichia coli. Replacement therapy with oral fluids and electrolytes may be sufficient for mild to moderate disease; those who develop diarrhea with ≥3 loose stools in an 8-hour period (especially if associated with nausea, vomiting, abdominal cramps, fever, or blood in the stools) may benefit from short-term anti-infectives. Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin, ofloxacin) usually drugs of choice when treatment indicated; co-trimoxazole also has been recommended as an alternative when fluoroquinolones cannot be used (e.g., in children).

Prevention of travelers’ diarrhea in individuals traveling forrelatively short periods to areas where enterotoxigenic E. coli and other causative bacterial pathogens (e.g., Shigella) are known to be susceptible to the drug. CDC and others do not recommend anti-infective prophylaxis in most individuals traveling to areas of risk; the principal preventive measures are prudent dietary practices. If prophylaxis is used (e.g., in immunocompromised individuals such as those with HIV infection), a fluoroquinolone (ciprofloxacin, levofloxacin, ofloxacin, norfloxacin) is preferred. Resistance to co-trimoxazole is common in many tropical areas.

Treatment of enteritis caused by susceptible Shigella flexneri or S. sonnei when anti-infectives are indicated.

Treatment of dysentery caused by enteroinvasive E. coli (EIEC). AAP suggests that an oral anti-infective (e.g., co-trimoxazole, azithromycin, ciprofloxacin) can be used if the causative organism is susceptible.

Treatment of diarrhea caused by enterotoxigenic E. coli (ETEC) in travelers to resource-limited countries. Optimal therapy not established, but AAP suggests that use of co-trimoxazole, azithromycin, or ciprofloxacin be considered if diarrhea is severe or intractable and if in vitro testing indicates the causative organism is susceptible. A parenteral regimen should be used if systemic infection is suspected.

Role of anti-infectives in treatment of hemorrhagic colitis caused by shiga toxin-producing E. coli (STEC; formerly known as enterohemorrhagic E. coli) is unclear; most experts would not recommend use of anti-infectives in children with enteritis caused by E. coli 0157:H7.

Treatment of GI infections caused by Yersinia enterocolitica or Y. pseudotuberculosis. These infections usually are self-limited, but IDSA, AAP, and others recommend anti-infectives for severe infections, when septicemia or other invasive disease occurs, and in immunocompromised patients. Other than decreasing the duration of fecal excretion of the organism, a clinical benefit of anti-infectives in management of enterocolitis, pseudoappendicitis syndrome, or mesenteric adenitis caused by Yersinia has not been established.

Respiratory Tract Infections

Treatment of acute exacerbation of chronic bronchitis caused by susceptible S. pneumoniae or H. influenzae when the clinician makes the judgment that the drug offers some advantage over use of a single anti-infective.

A drug of choice for treatment of upper respiratory tract infections and bronchitis caused by H. influenzae; an alternative to penicillin G or penicillin V for treatment of respiratory tract infections caused by S. pneumoniae.

Alternative for treatment of infections caused by Legionella micdadei (L. pittsburgensis) or L. pneumophila.

Urinary Tract Infections (UTIs)

Treatment of UTIs caused by susceptible E. coli, Klebsiella, Enterobacter, Morganella morganii, Proteus mirabilis, or P. vulgaris. A drug of choice for empiric treatment of acute uncomplicated UTIs.

Brucellosis

Treatment of brucellosis; alternative when tetracyclines are contraindicated (e.g., children). Used alone or in conjunction with other anti-infectives (e.g., streptomycin or gentamicin and/or rifampin), especially for severe infections or when there are complications (e.g., endocarditis, meningitis, osteomyelitis).

Burkholderia Infections

Treatment of infections caused by Burkholderia cepacia. Co-trimoxazole considered drug of choice; ceftazidime, chloramphenicol, or imipenem are alternatives.

Treatment of melioidosis caused by susceptible B. pseudomallei; used in multiple-drug regimen with chloramphenicol and doxycycline. Ceftazidime or imipenem monotherapy may be preferred. B. pseudomallei is difficult to eradicate and relapse of melioidosis is common.

Cholera

Treatment of cholera caused by Vibrio cholerae. Alternative to tetracyclines; used as an adjunct to fluid and electrolyte replacement in moderate to severe disease.

Cyclospora Infections

Treatment of infections caused by Cyclospora cayetanensis. The drug of choice.

Granuloma Inguinale (Donovanosis)

Treatment of granuloma inguinale (donovanosis) caused by Calymmatobacterium granulomatis. CDC recommends doxycycline or co-trimoxazole.

Isosporiasis

Treatment of isosporiasis caused by Isospora belli. The drug of choice.

Listeria Infections

Treatment of infections caused by Listeria monocytogenes; a preferred alternative to ampicillin in penicillin-allergic patients.

Mycobacterial Infections

Treatment of cutaneous infections caused by Mycobacterium marinum; alternative to minocycline.

Nocardia Infections

Treatment of infections caused by Nocardia, including N. asteroides, N. brasiliensis, and N. caviae. Drugs of choice are co-trimoxazole or a sulfonamide alone (e.g., sulfisoxazole, sulfamethoxazole).

Pertussis

Treatment of the catarrhal stage of pertussis to potentially ameliorate the disease and reduce its communicability. Recommended by CDC, AAP, and others as an alternative to erythromycin.

Prevention of pertussis in household and other close contacts (e.g., day-care facility attendees) of patients with the disease. Alternative to erythromycin.

Plague

Has been used for postexposure prophylaxis of plague. Although recommended by CDC and others for such prophylaxis in infants and children <8 years of age, efficacy of the drug for prevention of plague is unknown. Most experts (e.g., CDC, AAP, the US Working Group on Civilian Biodefense, US Army Medical Research Institute of Infectious Diseases) recommend oral ciprofloxacin or doxycycline for postexposure prophylaxis in adults and most children. Postexposure prophylaxis recommended after high-risk exposures to plague, including close exposure to individuals with naturally occurring plague, during unprotected travel in active epizootic or epidemic areas, or laboratory exposure to viable Yersinia pestis.

Has been used for treatment of plague, but appears to be less effective than other anti-infectives used for treatment of the disease (e.g., streptomycin, gentamicin, tetracycline, doxycycline, chloramphenicol). Because of lack of efficacy, some experts state that co-trimoxazole should not be used for the treatment of pneumonic plague.

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia

Treatment of Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP). Initial drug of choice for most patients with PCP, including HIV-infected individuals.

Prevention of initial episodes of PCP (primary prophylaxis) in immunocompromised individuals at increased risk, including HIV-infected individuals. Drug of choice.

Long-term suppressive or chronic maintenance therapy (secondary prophylaxis) to prevent recurrence following an initial PCP episode in immunocompromised patients, including HIV-infected individuals. Drug of choice.

Toxoplasmosis

Prevention of toxoplasmosis encephalitis (primary prophylaxis) in HIV-infected adults, adolescents, and children who are seropositive for Toxoplasma IgG antibody. Drug of choice.

Not recommended for long-term suppressive or chronic maintenance therapy (secondary prophylaxis) to prevent recurrence of toxoplasmosis encephalitis; regimen of choice for secondary prophylaxis of toxoplasmosis is sulfadiazine and pyrimethamine (with leucovorin).

Typhoid Fever and Other Salmonella Infections

Alternative for treatment of typhoid fever (enteric fever) caused by susceptible Salmonella typhi. Drugs of choice are fluoroquinolones and third generation cephalosporins (e.g., ceftriaxone, cefotaxime); consider that multidrug-resistant strains of S. typhi (strains resistant to ampicillin, amoxicillin, chloramphenicol, and/or co-trimoxazole) reported with increasing frequency.

Alternative for treatment of gastroenteritis caused by nontyphoidal Salmonella.

Wegener’s Granulomatosis

Treatment of Wegener’s granulomatosis. Effect on long-term morbidity and mortality unclear, but may prevent relapse and reduce need for cytotoxic (e.g., cyclophosphamide) and corticosteroid therapy in some patients.

Whipple’s Disease

Treatment of Whipple’s disease caused by Tropheryma whippelii. Alternative or follow-up to penicillin G.

• Generic Name: norepinephrine
• Dosage Forms: n.a.
• Other Brand Names: Levophed, Levophed Bitartrate

Used as adjunctive therapy to produce vasoconstriction and maintain BP in the management of certain acute hypotensive states (e.g., pheochromocytomectomy, sympathectomy, poliomyelitis, spinal anesthesia, MI, septicemia, blood transfusion, drug reactions).

Pressor therapy is not a substitute for replacement of blood, plasma, fluids, and/or electrolytes. Correct blood volume depletion as fully as possible before administration.

The Surviving Sepsis Campaign International Guidelines for Management of Sepsis and Septic Shock recommend norepinephrine as the vasopressor of choice in adults with septic shock; if adequate BP not achieved, vasopressin or epinephrine may be added. Vasopressin also may be given in conjunction with norepinephrine to reduce dosage requirements of norepinephrine.

Also used to provide vasopressor support in other types of shock (e.g., cardiogenic, hemorrhagic), generally as a temporary measure until underlying cause can be treated.

In patients who are hypotensive from blood volume deficits, manufacturer states to use norepinephrine only as an emergency measure to maintain coronary and cerebral artery perfusion until blood volume replacement therapy can be completed.

Early revascularization is standard of care in patients with cardiogenic shock; individualize use of vasopressors in this setting.

Has been used to treat hypotension during spinal anesthesia; however, other vasopressors with a longer duration (e.g., phenylephrine) more commonly used.

Used adjunctively in the management of cardiac arrest to restore and maintain adequate BP after an effective heartbeat and ventilation have been established by other means.

High-quality CPR and defibrillation are the only proven interventions to increase survival to hospital discharge in ACLS. Other resuscitative efforts, including drug therapy, are considered secondary and should be performed without compromising the quality and timely delivery of chest compressions and defibrillation.

Principal goal of pharmacologic therapy during cardiac arrest is to facilitate the return of spontaneous circulation (ROSC), and epinephrine is the drug of choice for this use. Vasoactive drugs such as norepinephrine may be used for hemodynamic support following resuscitation.