Which medications in the drug class Antibiotics are used in the treatment of Proteus Infections?

Updated: Mar 03, 2020
  • Author: Shirin A Mazumder, MD, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
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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.

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