Broad penicillin

Bacteria produce chromosomady and R-plasmid (resistance factor) mediated P-lactamases. The plasmid-mediated enzymes can cross interspecific and intergeneric boundaries. This transfer of resistance via plasmid transfer between strains and even species has enhanced the problems of P-lactam antibiotic resistance. Many species previously controded by P-lactam antibiotics are now resistant. The chromosomal P-lactamases are species specific, but can be broadly classified by substrate profile, sensitivity to inhibitors, analytical isoelectric focusing, immunological studies, and molecular weight deterrnination. Individual enzymes may inactivate primarily penicillins, cephalosporins, or both, and the substrate specificity predeterrnines the antibiotic resistance of the producing strain. Some P-lactamases are produced only in the presence of the P-lactam antibiotic (inducible) and others are produced continuously (constitutive). 

Chemical Modification. The chemistry and synthetic strategies used in the commercial synthesis of cephalosporins have been reviewed (87) and can be broadly divided into ( /) Selection of starting material penicillin precursors must be rearranged to the cephalosporin nucleus (2) cleavage of the acyl side chain of the precursor (2) synthesis of the C-7 and C-3 side-chain precursors (4) acylation of the C-7 amino function to introduce the desked acylamino side chain (5) kitroduction of the C-3 substituent and 6) protection and/or activation of functional groups that may be requked. 

Norfloxacin (1, R = C2H5, R = H), a typical example, exhibits broad-spectrum activity and is useful in the treatment of upper respiratory tract and urinary infections [7] Lomefloxacin (2), a very recent introduction, is a third-generation product that, given once daily, is especially useful against pathogens resistant to cephalosponns, penicillins, and aminoglycosides [4] Floxacillin (J) is a stable, orally active antibacterial with improved activity over thenonfluonnated product (cloxacillin) [5]... 

Widespread clinical acceptance continues to be accorded to the cephalosporins, and the field is extremely active as firms search for the ultimate contender. Among the characteristics desired is retention of the useful features of the older members (relatively broad spectrum, less antigenicity than the penicillins, relative insensitivity toward 3-lactamases, and convenience of administration) while adding better oral activity and broader antimicrobial activity (particularly potency against Pseudomonas, anaerobes, meningococci, cephalosporinase-carrying organisms, and the like). To a considerable extent these objectives have been met, but the price to the patient has been dramatically increased. 

One of the most popular orally active penicillins in present clinical use is amoxicillin (12). Its oral effectiveness and broad spectrum of activity against common pathogens as well as its better absorption than its closest precedent competitor, ampicillin (14), largely accounts for this. Higher blood and tissue levels of antibiotics is another means of dealing with resistance. In an attempt to achieve yet further improvements in oral bioavailability and hence blood and ti.ssue levels of amoxicillin, the prodmg fumoxicillin (13) is prepared from amoxicillin (12) by treatment with furfural [3]. The imine moiety is less basic than the primary amine so that the isoelectric point of fumoxicillin is more on the acid side than is that of amoxicillin. 

Sheehan s concentrated attack upon the penicillin synthesis problem began in 1948 and was conducted on a broad front. It was anticipated at the outset that the formidable penicillin V molecule would succumb to organic synthesis only in the event that new powerful and selective methods of organic synthesis are brought to bear on the problem. But, in addition, and perhaps more importantly, these new synthetic methods must be mild enough to contend with... 

Because the natural penicillins have been used for many years, drug-resistant strains of microorganisms have developed, making the natural penicillins less effective than some of the newer antibiotics in treating a broad range of infections. Bacterial resistance has occurred within tire penicillins. Bacterial resistance is the ability of bacteria to produce substances that inactivate or destroy the penicillin. One example of bacterial resistance is tiie ability of certain bacteria to produce penicillinase, an enzyme that inactivates penicillin. The penicillinase-resistant penicillins were developed to combat this problem. 

Promoting Optimal Response to Therapy The results of a culture and sensitivity test take several days because time must be allowed for the bacteria to grow on the culture media However, infections are treated as soon as possible In a few instances, the primary health care provider may determine that a penicillin is the treatment of choice until the results of the culture and sensitivity tests are known. In many instances, the primary health care provider selects a broad-spectrum antibiotic (ie, an antibiotic that is effective against many types or strains of bacteria) for initial treatment because of the many penicillin-resistant strains of microorganisms. 

Acylation of 6-APA with appropriate substances results in new penicillins being produeed whieh differ only in the nature of the side chain (Table 5.1 Fig. 5.2). Some of these penieillins have considerable activity against Gram-negative as well as Grampositive baeteria, and are thus broad-spectrum antibiotics. Pharmacokinetic properties may also be altered. 

Penicillins (amoxicillin, ampicillin) Broad-spectrum antibiotics may alter intestinal flora, Decrease efficacy of COCs, although the... 

T cells control these learned responses and decide which tools to use in the reaction. Sometimes they choose several different tools at once, and multiple reactions ensue, such as when a person becomes sensitized to penicillin and has not only anaphylaxis but hemolytic anemia and serum sickness. There are different types of T cells, and they communicate either directly with other cells or by chemical messages called cytokines. The pattern of cytokines released is one way T cells have of determining which kind of response will occur. They are broadly called Thl andTh2 responses, with Thl mostly responding to infections and Th2 often producing allergy or asthma. 

Broad intravenous antibiotic coverage for the encapsulated organisms can include ceftriaxone or cefotaxime. For patients with true cephalosporin allergy, clindamycin may be used. If staphylococcal infection is suspected owing to previous history or the patient appears acutely ill, vancomycin should be initiated. Macrolide antibiotics, such as erythromycin and azithromycin, may be initiated if Mycoplasma pneumonia is suspected. While the patient is receiving broad-spectrum antibiotics, their regular use of penicillin for prophylaxis can be suspended. Fever should be controlled with acetaminophen or ibuprofen. Because of the risk of dehydration during infection with fever, increased fluid may be needed.6,27... 

Ampicillin is the standard penicillin that has broad-spectrum activity, and is the drug of choice for enterococci sensitive to penicillin. Amoxicillin is frequently used as well. Increasing E. coli resistance has limited amoxicillin use in acute cystitis. Amoxicillin-clavulanate is empirically preferred due to resistance. 

Lactams are a broad class of antibiotics that include penicillin derivatives, cephalosporins, monobactams, carbapenems, and clavams (/8-lactamase inhibitors). The metabolic engineering of penicillin and cephalosporins production has been summarized by several good reviews [71,72], so the focus here is clavulanic acid, which has attracted interest in recent years. 

A recent prospective study of AAD and CDAD in five Swedish hospitals showed an increased risk of AAD with cephalosporins, clindamycin and broad-spectrum penicillins [42], While CDAD is well recognized as the most common nosocomial gastrointestinal pathogen, some... 

The answer is b. (Hardman, pp 1077—1086.) Piperacillin is a broad-spectrum, semisynthetic penicillin for parenteral use. Its spectrum of activity includes various Gram-positive and Gram-negative organisms including Pseudomonas. The indications for piperacillin are similar to those for car-benicillin, ticarcillin, and mezlocillin, with the primary use being sus-... 

The answer is b. (Hardman, p 1077.) Unlike the other listed drugs, oxacillin is resistant to penicillinase. The other four agents are broad-spectrum penicillins, while oxacillin is generally specific for Gram-positive microorganisms Use of penicillinase-resistant penicillins should be resewed for infections caused by penicillinase-producing staphylococci... 

Only patients with severe AP complicated by necrosis should receive infection prophylaxis with broad-spectrum antibiotics. Agents that cover the range of enteric aerobic gram-negative bacilli and anaerobic organisms should be started within the first 48 hours and continued for 2 to 3 weeks. Imipenem-cilastatin (500 mg every 8 hours) may be most effective a fluoroquinolone (e.g., ciprofloxacin, levofloxacin) with metronidazole should be considered for penicillin-allergic patients. 

In search of novel and more effective antibacterial agents, numerous /1-lactam antibiotics bearing a pyridazine core have been synthesized mainly in Japan. Thus, the penicillin derivative (125) characterized by a 3-hydroxypyridazine-4-carboxamido subunit has been patented as a broad-spectrum bactericide [342-345] likewise, the corresponding cephalosporin analogue has been claimed in a patent [346]. 

The efficacy of penicillin-type antibiotics is constrained by the ability of bacteria to induce enzymes for their destruction. In relation to this problem, Page and coworkers (Buckwell et al., 1988a,b) have studied the hydrolysis of acylated penicillins [55] and cephalosporins [56] catalysed by a bacterial /3-lactamase (Tables A6.9 and A6.10). It is noteworthy that the two series of substrates show quite different responses to changes in the length of the acyl side chain (C2 to C12). For the penicillins, which are cleaved much more efficiently, there is a broad maximum in the kinetic parameters around C5 to C7, whereas for the cephalosporins there is a linear increase in kc/KM and... 

Penicillinacylase is used industrially to catalyze the hydrolytic removal of the side chain in naturally occurring penicillins such as benzylpenicillin (4.49) and phenoxymethylpenicillin (4.50). The nucleus 6-aminopenicillic acid (4.48) is then used as the starting material for the preparation of semisynthetic penicillins. Appropriate acylation of the 6-NH2 group leads to )3-lactamase-stable and broad-spectrum penicillins. 

Amoxicillin is a broad spectrum penicillin antibiotic. Antibiotics tend to cause pseudomembranous colitis as a result of colonisation of the colon by Clostridium difficile following antibiotic therapy. 

A patient who is taking phenytoin and is hypersensitive to penicillin requires a broad-spectrum antibacterial agent for a respiratory tract infection. 

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