Medication Summary
Serious and occasionally fatal hypersensitivity (ie, anaphylactoid) reactions have occurred in patients receiving antibiotics. These reactions are more likely to occur in persons with a history of sensitivity to multiple allergens. Cross-sensitivity between penicillins and cephalosporins has occurred. If a reaction occurs, discontinue the implicated drug unless the condition is life threatening and amenable only to therapy with that antibiotic. Serious anaphylactoid reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should also be used as indicated.
Pseudomembranous colitis has been reported with nearly all antibacterial agents and has ranged in severity from mild to life threatening. This diagnosis must therefore be considered in patients who present with diarrhea subsequent to the administration of antibacterial agents. Antibiotic treatment alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of antibiotic colitis. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate-to-severe cases, consider treatment with fluids and electrolytes, protein supplementation, and an antibacterial drug effective against C difficile.
Antibiotic therapy requires constant observation for signs of overgrowth of nonsusceptible organisms, including fungi. Overgrowth more usually occurs in the setting of chronic UTIs or in patients with indwelling catheters than in uncomplicated UTIs. If superinfection occurs (usually involving Aerobacter, Pseudomonas, or Candida organisms), discontinue the offending drug and/or institute appropriate therapy. As with any potent agent, it is advisable to periodically check for organ system dysfunction during prolonged therapy, to include the renal, hepatic, and hematopoietic systems. This measure is particularly important in premature infants, neonates, and other infants.
P mirabilis remains susceptible to nearly all antimicrobials except tetracycline. Resistance does not appear to be a significant clinical factor, but 10-20% of strains can acquire resistance to ampicillin and first-generation cephalosporins. Acquisition of resistance to extended-spectrum alpha-lactamases remains uncommon, but concern exists regarding the emergence of extended-spectrum beta-lactamase–producing organisms, most notably E coli. [1, 2, 3, 4] P mirabilis is likely to be sensitive to ampicillin; broad-spectrum penicillins (eg, ticarcillin, piperacillin); first-, second-, and third-generation cephalosporins; imipenem; and aztreonam. [5]
P vulgaris and P penneri are resistant to ampicillin and first-generation cephalosporins. Activation of an inducible chromosomal beta-lactamase (not found in P mirabilis) occurs in up to 30% of these strains. Imipenem, fourth-generation cephalosporins, aminoglycosides, TMP/SMZ, and quinolones have excellent activity (90-100%). Consult the local infectious disease sensitivity surveillance for appropriate empiric therapy.
In addition, the use of chlorhexidine and triclosan in closed urinary catheterization systems and drug-impregnated catheters reduce the incidence of Proteus UTI in patients with long-term indwelling urinary catheters. [6, 7] While the use of these types of catheters for Proteus UTIs is helpful in containing the migration of Proteus in experimental models, this practice is not widespread, as other, more common, uropathogens are resistant to the drugs used in these systems.
A vaccine derived from purified mannose-resistant Proteus -like (MR/P) fimbriae proteins has been proven to prevent infection in mouse models and is under clinical research, but it is not available commercially. Vaccine description is beyond the scope of this article.
Antibiotics
Class Summary
Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.
Ceftriaxone (Rocephin)
Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Bactericidal activity results from inhibiting cell wall synthesis by binding to one or more penicillin-binding proteins. Highly stable in presence of beta-lactamases, both penicillinase and cephalosporinase, of gram-negative and gram-positive bacteria. Approximately 33-67% of dose excreted unchanged in urine, and remainder secreted in bile and ultimately in feces as microbiologically inactive compounds. At 1-3 h after 1-g IV dose, average concentrations determined were 581 mcg/mL in gallbladder bile, 788 mcg/mL in common duct bile, 898 mcg/mL in cystic duct bile, 78.2 mcg/g in gallbladder wall, and 62.1 mcg/mL in concurrent plasma. In healthy adult subjects, over 0.15-3 g dose, range of elimination half-life is 5.8-8.7 h. Apparent volume of distribution is 5.78-13.5 L, plasma clearance is 0.58-1.45 L/h, and renal clearance is0.32-0.73.
L/h. Reversibly bound to human plasma proteins, and binding has been reported to decrease from 95% bound at plasma concentrations < 25 mcg/mL to 85% bound at 300 mcg/mL.
Trimethoprim and sulfamethoxazole, TMP/SMZ (Septra, Septra DS, Bactrim)
Blocks 2 consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria. SMZ inhibits bacterial synthesis of dihydrofolic acid by competing with PABA. TMP blocks production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting required enzyme, dihydrofolate reductase. In vitro studies indicate that bacterial resistance develops more slowly with TMP/SMZ combination than with either component alone. In vitro serial dilution tests indicate that the spectrum of antibacterial activity includes common urinary tract pathogens with exception of P aeruginosa. The following organisms are usually susceptible: E coli, Klebsiella and Enterobacter species, Morganella morganii,P mirabilis, and indole-positive Proteus species, including P vulgaris.
Additional information for PO use:
PO products available: Tab (80 mg TMP/400 mg SMZ); double-strength (DS) tab (160 mg TMP/800 mg SMZ); susp (TMP 40 mg/5mL and SMZ 200 mg/5 mL)
Levofloxacin (Levaquin)
Mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination. Has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. Fluoroquinolones, including levofloxacin, differ in chemical structure and mode of action from aminoglycosides, macrolides, and beta-lactam antibiotics, including penicillins. Fluoroquinolones may therefore be active against bacteria resistant to these antimicrobials.
Ampicillin (Omnipen, Polycillin)
Like benzyl penicillin, is bactericidal against sensitive organisms during active multiplication. Inhibits biosynthesis of cell wall mucopeptide. Not effective against penicillin-producing bacteria, particularly resistant staphylococci. All strains of Pseudomonas and most strains of Klebsiella and Aerobacter organisms are resistant.
Aztreonam (Azactam)
Exhibits potent and specific activity in vitro against a wide spectrum of gram-negative aerobic pathogens, including P aeruginosa. Active over a pH range of 6-8 in vitro, as well as in presence of human serum and under anaerobic conditions. Combined with aminoglycosides, demonstrates synergistic activity in vitro against most strains of P aeruginosa. Duration of therapy depends on severity of infection and continues for at least 48 h after patient is asymptomatic or evidence of bacterial eradication is obtained. Doses smaller than indicated should not be used. Transient or persistent renal insufficiency may prolong serum levels. After an initial loading dose of 1 or 2 g, reduce dose by one half for estimated CrCl of 10-30 mL/min/1.73/m2. When only serum creatinine concentration is available, the following formula (based on sex, weight, and age) can approximate CrCl. Serum creatinine should represent a steady state of renal function.
Males: CrCl = [(weight in kg)(140 - age)] ÷(72 X serum creatinine in mg/dL)
Females: 0.85 X above value.
In patients with severe renal failure (CrCl < 10 mL/min/1.73/m2) and those supported by hemodialysis, usual dose of 500 mg, 1 g, or 2 g is initially administered. Maintenance dose is one fourth of usual initial dose given at usual fixed interval of 6, 8, or 12 h.For serious or life-threatening infections, supplement maintenance doses with one eighth of initial dose after each hemodialysis session. Elderly persons may have diminished renal function. Renal status is a major determinant of dosage in these patients. Serum creatinine may not be an accurate determinant of renal status. Therefore, as with all antibiotics eliminated by kidneys, obtain estimates of CrCl, and make appropriate dosage modifications. Insufficient data are available regarding IM administration to pediatric patients or dosing in pediatric patients with renal impairment. Administered IV only to pediatric patients with normal renal function.
Ticarcillin and Clavulanate (Timentin)
Demonstrates substantial in vitro bactericidal activity against gram-positive and gram-negative organisms. Not stable in presence of penicillinase. Exhibits in vitro synergism with aminoglycosides (gentamicin, tobramycin, amikacin) against certain strains of P aeruginosa.
Imipenem and cilastatin (Primaxin)
Demonstrates in vitro activity against a wide range of gram-positive and gram-negative organisms. Because of its broad spectrum of bactericidal activity against gram-positive and gram-negative aerobic and anaerobic bacteria, it is useful for the treatment of mixed infections and as presumptive therapy prior to the identification of the causative organisms. Although clinical improvement has been observed in patients with cystic fibrosis, chronic pulmonary disease, and lower respiratory tract infections caused by P aeruginosa, bacterial eradication may not necessarily be achieved.
Potent inhibitor of beta-lactamases from certain gram-negative bacteria that are inherently resistant to most beta-lactam antibiotics (eg, P aeruginosa,Serratia and Enterobacter species). As with some other beta-lactam antibiotics, some strains of P aeruginosa may develop resistance fairly rapidly during treatment. Therefore, perform periodic susceptibility testing when clinically appropriate. Base total daily dosage on type or severity of infection and administer in equally divided doses based on consideration of degree of susceptibility of the pathogen(s), renal function, and body weight. Dosage recommendations reflect quantity of imipenem component administered. Corresponding amount of cilastatin is also present in solution. A product that is only for IM use is available.
Piperacillin and Tazobactam (Zosyn)
Exerts bactericidal activity by inhibiting both septum and cell wall synthesis. Active against various gram-positive and gram-negative aerobic and anaerobic bacteria. Inactivated in vitro by staphylococcal beta-lactamase and beta-lactamase produced by gram-negative bacteria. Its broad spectrum of bactericidal activity against gram-positive and gram-negative aerobic and anaerobic bacteria makes it particularly useful for treatment of mixed infections and presumptive therapy prior to the identification of the causative organisms. Administered IM or IV.
Gentamicin (Garamycin)
Bactericidal antibiotic (demonstrated by in vitro tests) that inhibits normal protein synthesis in susceptible microorganisms. Active against a wide variety of pathogenic bacteria, including E coli, Proteus species (indole-positive and indole-negative), Pseudomonas aeruginosa; species of Klebsiella, Enterobacter, and Serratia; Citrobacter species; and Staphylococcus species (including penicillin- and methicillin-resistant strains). The following organisms are usually resistant to aminoglycosides: Streptococcus pneumoniae, most species of streptococci, particularly group D and anaerobic organisms (ie, Bacteroides or Clostridium species). In vitro studies demonstrate that an aminoglycoside combined with an antibiotic that interferes with cell wall synthesis may act synergistically against some group D streptococcal strains.
Combination of gentamicin and penicillin G has a synergistic bactericidal effect against virtually all strains of Streptococcus faecalis and its variants (ie, Streptococcus faecalis var liquefaciens,Streptococcus faecalis var zymogenes), Streptococcus faecium, and Streptococcus durans. An enhanced killing effect against many of these strains occurs in vitro when combined with ampicillin, carbenicillin, nafcillin, or oxacillin. Combined effect of gentamicin and carbenicillin is synergistic for many strains of P aeruginosa. In vitro synergism against other gram-negative organisms occurs when combined with cephalosporins.
-
After 24 hours, this inoculated MacConkey agar culture plate cultivated colonial growth of gram-negative, rod-shaped, and facultatively anaerobic Proteus vulgaris bacteria. Courtesy of the CDC.
