Ampicillin and sulbactam

Sulbactam is marketed by Pfizer, in combination with ampicillin under the name of Unasyn and in combination with cefoperazone under the name of Sulperazon, both as injectable products. The oral version of sulbactam is the mutual pro-drug of sulbactam and ampicillin (sultamicillin) and is sold by Pfizer under the brand name of Unasyn Oral. Uses of Unasyn Oral are similar to those of Augmentin and include infections of the upper and lower... 

Another (3-laotamase-disabling agent is sulbactam. Sulbactam is prepared by partial chemical synthesis from penioillins. The oxidation of the sulfur atom to a sulfone greatly enhances the potency of sulbactam. The combination of sulbactam and ampicillin (Unasyn) is now olinically popular. 

L B. The patient has complicated urinary tract infection and nonsevere sepsis syndrome caused by P. aeruginosa. Effective antibiotics for Pseudomonas spp. include mezlocillin, piperacillin, piperacillin-tazobactam, ticarcillin, and ticarciUin-clavulanate. The carbapenems (imipenem and meropenem) and the monobactam (aztreonam) are also active against P. aeruginosa. Ampicillin-sulbactam and cefazolin are ineffective against P. 

Current commercial inhibitors of /3-lactamases include clavulanic acid (an oxapenam see Table 1), sulbactam, and tazobactam (two penam sulfones see Table 1). They are effective only against the class A serine /3-lactamases and they are administrated in the form of antibiotic/inhibitor combinations <2006BP930> Augmentin (amoxicillin/clavulanic acid), Timentin (ticarcillin/clavulanic acid), Unasyn (ampicillin/Sulbactam), Zosyn (piperacillin/tazobactam). 

Amoxicillin/clavulanate and ampicillin/sulbactam are useful for treating lower respiratory infections, otitis media, and sinusitis caused by p-lactamase-producing strains of H. influenzae (see Table 11-3). They are also... 

Like clavulanic acid, sulbactam possesses only weak antibacterial activity but displays synergistic activity in combination with many penicillins and cephalosporins. Comparative synergistic activity of sulbactam and other y5-lactamase inhibitors, in combination with ampicillin and amoxycillin, is presented in later sections. 

Continuing use of the third-generation cephalosporins and the introduction of p-lactamase inhibitor combinations (clavulanate with amoxycillin or ticarcillin, sulbactam with ampicillin, and tazobactam with piperacillin see section 4.2) resulted in the appearance of plasmids encoding class C P-lactamases. After several unconfirmed reports, the first proof that a class C P-lactamase had been captured on a plasmid came in 1990 when transmissible resistance to a-methoxy and oxyimino-P-lactams was shown to be mediated by an enzyme whose gene was 90% identical to the ampC gene of E. cloacae. They have subsequently been found worldwide. Strains with plasmid-mediated AmpC enzymes are typically resistant to aminopenicillins (ampicillin or amoxycillin), carboxypenicillins (carbenicillin or ticarcillin) and ureidopenicillins (piperacillin). The enzymes also provide resistance to the oxyimino cephalosporins (ceftazidime, cefo-... 

Clavulanic acid was discovered in 1976 and is a 15-lactam antibiotic with low antibiotic activity, but does protect 3-lactamase-sensitive compounds of high intrinsic activity such as benzylpenicillin, ampicillin, and amoxicillin from 3-lactamase destruction. Subsequently other 3-lactamase inhibitors such as sulbactam and tazobactam were developed [4]. 

Many in vitro studies have firmly established a synergism between sulbactam and various P-lactam antibiotics including piperacillin, amdinocillin, ampicillin, and penicillin G. These studies included bacterial strains resistant to ampicillin or penicillin G alone, which became sensitive upon addition of sulbactam. Carbenicillin-resistant Pseudomonas, however, was not potentiated. 

Belliveau, P.P. Nightingale, C.H. Quintiliani, R. Stability of aztreonam and ampicillin sodium-sulbactam sodium in 0.9% sodium chloride injection. Am.J.Hosp.Pharm., 1994, 51, 901-904... 

Immunologic There have been further reports of drug rash with eosinophilia and systemic symptoms (DRESS) in patients taking sulfasalazine, a 47-year-old white Brazilian woman who developed DRESS after 8 weeks [104" ], a 60-year-old man with polyarthritis who also developed fulminant liver failure after additional vancomycin treatment [lOS ], and a 68-year-old woman in whom the reaction may have been precipitated by the addition of sulbactam -f ampicillin [lob ll. In another case, drug-induced hypersensitivity syndrome was associated with reactivation of an infection with human herpesvirus-6 in a 15-year-old boy with juvenile rheumatoid arthritis who was taking sulfasalazine [107 ]. 

Sulbactam (25, R = R = H, R" = R " = dl ) is produced by Pfizer. The oral version of sulbactam in combination with ampicillin is called Unasyn Oral which is the mutual prodmg sultamicillin. Two sulbactam parenteral products are sold, a combination product with ampicillin called Unasyn and a combination with cefoperazone [62893-19-0] called Sulperazon. In addition, sulbactam is sold alone for parenteral use with any P-lactam antibiotic as Betamaze. In 1990 worldwide sales of sulbactam containing products were over 280 million. 

Complicated exacerbation FEV, less than 50% predicted Comorbid cardiac disease Greater than or equal to 3 exacerbations per year Antibiotic therapy in the previous 3 months Above organisms plus drug-resistant pneumococci, P-lactamase-producing H. influenzae and M. catarrhalis, Escherichia coli, Proteus spp., Enterobacter spp., Klebsiella pneumoniae Oral P-Lactam/P-Iactamase inhibitor (amoxicil 1 i n-clavulanate) Fluoroquinolone with enhanced pneumococcal activity (levofloxacin, gemifloxacin, moxifloxacin) Intravenous P-Iactam/P-Iactamase inhibitor (ampicillin-sulbactam) Second- or third-generation cephalosporin (cefuroxime, ceftriaxone) Fluoroquinolone with enhanced pneumococcal activity (levofloxacin, moxifloxacin)... 

If a patient aspirates his or her oral contents and pneumonia develops, then anaerobes and Streptococcus spp. are the primary pathogens. Antibiotics active against these organisms include penicillin G, ampicillin/sulbactam, clindamycin, and metronidazole. 

If the wound is associated with significant cellulitis and edema, systemic signs of infection, or possible joint or bone involvement, hospitalization and IV antibiotics (typically ampicillin-sulbactam 3 g IV every 6 hours) should be initiated. Bone and joint infections will require longer durations of therapy of up to 6 weeks.44... 

Pelvic Inflammatory Disease Cefotetan or cefoxitin with doxycycline 1. Clindamycin with gentamicin 2. Ampicillin-sulbactam with doxycycline 3. Ciprofloxacin with doxycycline and metronidazole... 

Levofloxacin 500 mg IV every 24 hours with or without metronidazole 500 mg IV every 8 hours Ampicillin-sulbactam, 3 g IV every 6 hours and doxycycline 100 mg PO or IV every 12 hours Oral... 

Treatment for septic patients with hospital-acquired, ventilator-acquired, and health care-associated pneumonia is dependent on risk factors for multi-drug resistant (MDR) organisms (Fig. 79-2). Recommended treatment for patients with no MDR risk factors are third-generation cephalosporins, fluoroquinolones, ampicillin-sulbactam, or ertapenem (see Table 79-3).35 Recommended treatment for patients with MDR risk factors are P-lactam/p-lactamase inhibitors (piperacillin-tazobactam), antipseudomonal cephalosporin, or carbapenem, plus an aminoglycoside, plus vancomycin or linezolid (see Table 79-3).35 If an aminoglycoside is undesirable, a antipseudomonal fluoroquinolone may be utilized with a P-lactam/p-lactamase inhibitor. 

When combined with a (i-lactam antibiotic, both clavulanic acid and sulbactam provide very effective treatments for general bacterial infections, and overcome the resistance that would otherwise been encountered due to the expression of (i-lactamases. Clavulanic acid is sold in combination with the antibiotic amoxicillin and sulbactam is sold in combination with ampicillin. 

Treatment options for patients requiring intravenous therapy include /J-lactam-/3-lactamase inhibitors (ampicillin-sulbactam or piperacillin-tazobactam), second-generation cephalosporins with antianaerobic activity (cefoxitin), and carbapenems. 

Aninoglycosides Gentamicin Tobramycin Amikacin Penicillins Ampicillin Ampicillin-sulbactam Ticarcillin-davulanate Piperacillin-tazobactam Cephalosporins, first-, second-, and third-generation... 

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