Drug
Mechanism
Indication
Dosing options
Drug interactions
Side effects
Monobactam (aztreonam)
Inhibition of cell wall mucopeptide synthesis
Strong activity against gram-negative bacteria; may be substituted for penicillins or cephalosporin
IV, IM
Few reported
Rash, GI upset, rarely toxic epidermal necrolysis
Streptogramin (quinupristin dalfopristin)
Inhibition of protein synthesis through binding to ribosomal subunits
Vancomycin-resistant infections
IV
Increased plasma concentration of drugs metabolized by CYP3A4 (includes fentanyl) [7]
Phlebitis with peripheral intravenous administration, arthralgias, myalgias, and increased levels of bilirubin
Polymyxins (polymyxin B polymyxin E)
Altered bacterial cytoplasmic membrane permeability through phospholipid binding
Specific gram-negative bacilli including E. coli, Klebsiella, and Pseudomonas aeruginosa; useful in treatment of severe urinary tract infections and sensitive strains of P. aeruginosa for patients with cystic fibrosis, neutropenia, and/or immune compromise
IV, IM, and topical for infections of the skin, mucous membranes, eyes, and ears
Few reported
Pain with IM injection, skeletal muscle weakness, potentiation of nondepolarizing muscle relaxants, and nephrotoxicity
Nitrofurantoin
Inhibition of bacterial enzymes and possibly cell wall synthesis
Uncomplicated mild urinary tract infections
PO
Probenecid decreases renal clearance
GI upset, rarely pneumonitis, neuropathies, chronic active hepatitis
Metronidazole
Deactivates bacterial enzymes
Most anaerobic gram-negative bacilli and clostridium species
PO, IV
Disulfiram-like reaction with concurrent alcohol ingestion
Dry mouth, metallic taste, nausea, and rarely pancreatitis and neuropathy
Monobactams
The most common in this class is aztreonam.
Mechanism of Action
Inhibits cell wall mucopeptide synthesis
Indication
Strong activity against gram-negative bacteria; may be used for penicillin or cephalosporin allergic patients due to lack of cross-reactivity
Dosing Options
IV, IM
Drug Interactions
Few reported
Side Effects
Rash, GI upset, rarely toxic epidermal necrolysis
Streptogramins
Quinupristin and dalfopristin are in the class of streptogramins.
Mechanism of Action
Bind to bacterial ribosomal subunits and inhibit protein synthesis
Indication
Vancomycin-resistant infections
Dosing Options
IV
Drug Interactions
Increase plasma concentrations of drugs such as fentanyl that depend on CYP3A4 for hepatic metabolism [7]
Side Effects
Phlebitis with peripheral intravenous administration, arthralgias, myalgias, and increased levels of bilirubin
Polymyxins
This class includes both polymyxin B and polymyxin E (colistimethate).
Mechanism of Action
Bind to phospholipids, altering their permeability and damaging the bacterial cytoplasmic membrane
Indication
Certain gram-negative bacilli including E. coli, Klebsiella, and Pseudomonas aeruginosa; useful in treatment of severe urinary tract infections and sensitive strains of P. aeruginosa, which are a significant problem for patients with cystic fibrosis, neutropenia, and/or immune system compromise
Dosing Options
IV, IM; topical for infections of the skin, mucous membranes, eyes, and ears
Drug Interactions
Few reported
Side Effects
Pain with IM injection, skeletal muscle weakness, potentiation of nondepolarizing muscle relaxants, and nephrotoxicity
Sulfonamides
Clinically useful sulfonamides include sulfisoxazole, sulfamethoxazole, sulfasalazine, sulfacetamide, trimethoprim, and trimethoprim-sulfamethoxazole.
Mechanism of Action
Competitive inhibitors of the bacterial enzyme responsible for the incorporation of para-aminobenzoic acid into the immediate precursor of folic acid; trimethoprim prevents the reduction of dihydrofolate to tetrahydrofolate by selectively inhibiting dihydrofolate reductase.
Indication
Uncomplicated urinary tract infections and H. influenza otitis media in children
Dosing Options
PO, IV
Drug Interactions
May increase the effect of oral anticoagulants, methotrexate, sulfonylurea, hypoglycemic drugs, and thiazide diuretics; indomethacin, probenecid, and salicylates may displace sulfonamides from plasma albumin and increase the concentrations of free drug in the plasma.
Side Effects
Allergic reactions ranging from skin rash to anaphylaxis, drug fever, hepatotoxicity (<0.1 %), acute hemolytic anemia, and agranulocytosis; hemolytic anemia may occur in patients with glucose-6-phosphate deficiency syndrome.
Nitrofurantoin
Mechanism of Action
Inhibits bacterial enzymes, possibly cell wall synthesis
Indication
Uncomplicated mild urinary tract infections
Dosing Options
PO
Drug Interactions
Probenecid decreases renal clearance.
Side Effect
GI upset, rarely pneumonitis, neuropathies, chronic active hepatitis
Metronidazole
Mechanism of Action
Deactivates bacterial enzymes
Indication
Most anaerobic gram-negative bacilli and Clostridium species
Dosing Options
PO, IV
Drug Interactions
Disulfiram-like reaction with concurrent alcohol ingestion
Side Effects
Dry mouth, metallic taste, nausea, and rarely pancreatitis and neuropathy
Antifungals
See Table 32.2.
Table 32.2
Antifungals
|
Drug |
Administration |
Indications |
Side effects |
Notes |
|---|---|---|---|---|
|
Nystatin |
PO, vaginal tablets, topical |
Candida |
Rare |
Candidal infections are common in immunosuppressed |
|
Amphotericin B |
IV |
Cryptococcus, histoplasmosis, coccidioidomycosis, blastomycosis, disseminated candidiasis |
Renal impairment possibly permanent, hypokalemia, hypomagnesemia, fever, chills, dyspnea during infusion, anemia, thrombocytopenia, seizures, allergic reactions |
Does not penetrate CSF or vitreous humor; intrathecal injection may be needed; decrease dose when Cr >3.5 |
|
Flucytosine |
PO |
In combination with amphotericin B |
Transaminitis and hepatomegaly |
Rapid resistance; clearance dependent on renal function |
|
Griseofulvin |
PO |
Fungal infections of skin, hair, nails |
Headache in up to 15 % (can be severe), peripheral neuritis, fatigue, blurred vision, syncope, hepatotoxicity |
Decreases activity of warfarin-like anticoagulants |
Antituberculous Drugs
Due to varying mechanisms and the possibility of antimicrobial resistance, a multidrug regimen is required for patients with active tuberculosis without known drug sensitivities. During the initial 2 months of treatment, a combination of daily isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin is employed, after which only isoniazid and rifampin are needed assuming the organism is drug sensitive. The goal of treatment is an additional 4 months of treatment or 3 months of negative sputum cultures. Active pulmonary tuberculosis with positive sputum cultures, on the other hand, must be treated in a negative pressure isolation room until three consecutive sputum cultures from separate days are negative [22].
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