Sulbactam

CAS Reglatry Na 68373-14-8 (sulbactam), 83031-43-0 (sulbactam benzathine), 69388-79-0 (sulbactam pivoxil), 69388-84-7 (sulbactam sodium) 

Sample preparation 1 mL Serum + 400 p.L 10 m mL zinc sulfate containing 350 j.g/mL benzoic acid, vortex for 30 s, centrifuge at 5500 g for 5 min, iiyect a 20 ixL aliquot of the supernatant. 

Guillaume, Y. Peyrin, E. Guinchard, C. Rapid determination of sulbactam and tazobactam in human serum by high-performance liquid chromatography. J.Chromatogr.B, 1995, 665, 363-371 

Sample preparation Filter (Amicon MPS-1 with YMT membrane) while centrifuging at 1500 g for 10 min, ii ject a 20 pL aliquot of the ultrafiltrate. 

Mobile phase MeOH buffer 1 1.5 (Prepare buffer by dissolving 1.791 g Na2HP04.12H20 and 0.780 g NaH2P04.2Ha0 in 10 L water, add tetrabutylammonium bromide to a final concentration of 5 mM.) 

---

Sugars, special Sugar trading Suhr s borate Sulbactam [68373-14-8]... 

Penam Sulfone B-Lactamase Inhibitors. Natural product discoveries stimulated the rational design of p-lactamase inhibitors based on the readily accessible penicillin nucleus. An early success was penicillanic acid sulfone, (2(5)-cis)-3,3-dimethyl-7-oxo-4,4-dioxide-4-thia-l-a2abicyclo [3.2.0]heptane-2-carboxylic acid [68373-14-8] (sulbactam) (25, R = = H, R" = R" = CH ), CgH NO S. The synthesis (118), microbiology (119—121),... 

Fig. 3. Species in the inhibition pathway for sulbactam with P-lactamase.

The 6-methoxymethylene penicillanic acid [93040-42-7] (31, R = CH OCH (2)-isomer, R" = R " = 3) designed to mimic the amino acrylate species found usiag clavulanic acid and sulbactam. Upon the reaction of this compound with the enzyme, the potential exists for further Michael addition to inactivate the enzyme. The compound is indeed a -lactamase inhibitor but no synergy data have been reported. The related imine stmcture... 

Although a broad range of P-lactamase inhibitors has been discovered, only clavulanic acid and sulbactam have been commercialized. Clavulanic acid (12, R = CH2OH, R = H), manufactured by SmithKlinp Beecham, is sold as an oral and parenteral product in combination with amoxicillin under the trade name Augmentin. A parenteral product in combination with ticarcillin [34787-01-4], C25H2gN20 S, has the trade name, Timentin. In 1990 worldwide sales of clavulanic acid containing products were about 725 million. 

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. 

Pd/C-hydrogen [6. An alternate synthesis of sulbactam is also available [7]. 

Inactivators of class A (3-lactamases (clavulanate, sulbactam, tazobactam) are themselves (3-lactams and act as suicide substrates. They can be used in... 

Augmentin-eombination of amoxicillin and clavulanic add Hmentin-combination of ticardllin and davulanicaad Unasyn-eombination of ampidllin and sulbactam Zosyn-eombination of piperadllin and tazobactam... 

Fig. 5.6 A, Nocardicin A B, 3-aminomonobactamic acid (3-AMA) C, aztreonam D, penicillanic acid sulphone (sodium salt) E, / -bromopenicillamc acid (sodium salt) F, tazobactam G, sulbactam.

Sulbactam (Tig. 5.6G) is a semisynthetic 6-desaminopenicillin sulphone stmcturally related to tazobactam. Not only is it an effective inhibitor of many /Mactamases but it is also active alone against certain Gram-negative bacteria. It is used in combination with ampicillin for clinical use. 

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 child is not admitted to the ICU, then the CDC recommends the use of intravenous cefuroxime, cefotaxime, ceftriaxone, or ampicillin-sulbactam plus a macrolide or azalide. If... 

Injection drug use MSSA GAS Gram-negatives Anaerobes CA-MRSAd Amoxicillin-clavulanate 500 mg every 8 hours Fluoroquinolone + clindamycin 300 mg every 6 hours TMP-SMX DS 1-2 tabs every 12 hours + clindamycin 300 mg every 6 hours Ampicillin-sulbactam 3 g every 6 hours Piperacillin-tazobactam 3.375 g every 6 hours Ceftriaxone 1 g daily + clindamycin 600 mg every 8 hours Ertapenem 1 g daily... 

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... 

Normal or inflamed Antianaerobic cephalosporins3 (discontinued immediately postoperation) 1. Ampicillin-sulbactam... 

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

Ampicillin, ampicil I in-sulbactam, ticarci 11 i n-clavu lanate, piperaci 11 in piperaci 11 i n-tazobactam Cephalosporins... 

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... 

Community-acquired pneumonia Health care-associated, ventilator-asociated, or nosocomial pneumonia (Early onset no risk factors for MDR pathogens) Third-generation cephalosporin plus a macrolide or doxycycline Third-generation cephalosporin OR Fluoroquinolone OR Ampicillin-sulbactam OR Ertapenem... 

Intra-abdominal Ampicillin-sulbactam OR Fluoroquinolone + metronidazole Piperacillin-tazobactam OR Imipenem or meropenem OR Cefepime plus metronidazole OR Ciprofloxacin or levofloxacin plus metronidazole... 

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. 

---