Antimicrobial parenteral

Solutions for external or oral use do not require sterilization but generally contain antimicrobial preservatives. Ophthalmic solutions and parenteral solutions require sterilization (qv). 

Mineral oil and paraffins should not be used, because these are not metabolized and may irritate tissue. Various other additives are needed for stabiUty, stefihty, and isotonicity antimicrobial preservatives, antioxidants (qv), chelating agents (qv), and buffers. No parenteral container material is completely inert to parenteral solvent systems. 

Cefmenoxime (61) is a third generation parenteral cephalosporin whose in vitro antimicrobial spectrum approximates that of cefotaxime. Its side chains consist of the common methyltetrazo lylthio group at C-3 and the familiar oximinoether aminothiazole moiety at C-7. It is synthesized... 

Prompt initiation of intravenous high-dose cidal antimicrobial therapy directed at the most likely pathogen (s) is essential due to the high morbidity and mortality associated with CNS infections parenteral (intravenous) therapy is administered for the full course of therapy for CNS infections to ensure adequate CSF penetration throughout the course of treatment. 

Patients with complicated typhoid fever (i.e., metastatic foci, ileal perforation, etc.) should receive parenteral therapy with ciprofloxacin 400 mg twice daily or ceftriaxone 2000 mg once daily. Antimicrobial therapy can be completed with an oral agent after initial control of the symptoms of typhoid fever. In persons with AIDS and a first episode of Salmonella bacteremia, a longer duration of antibiotic therapy (1-2 weeks of parenteral therapy followed by 4 weeks of oral fluoroquinolone) is recommended to prevent relapse of bacteremia. 

On the fifth day of antimicrobial treatment, determine if parenteral antimicrobial agents can be switched to oral agents to complete therapy. 

O A risk assessment should be performed at presentation of febrile neutropenia to identify low-risk patients for potential outpatient treatment (see Table 96-3). Patients who do not meet low-risk criteria should be hospitalized for parenteral administration of broad-spectrum antibacterials. The IDSA has published evidence-based guidelines for the management of febrile neutropenia5,12 (Fig. 96-1). The choice of initial antimicrobial agent(s) depends on the following factors ... 

Substances that have been used as preservatives for disperse systems include chlorocresol, chlorobutanol, benzoates, phenylmercuric nitrate, parabens, and others [76,77]. The use of cationic antimicrobial agents such as quaternary ammonium compounds (e.g., benzalkonium chloride) is contraindicated in many cases because they may be inactivated by other formulation components and/or they may alter the charge of the dispersed phase. Clay suspensions and gels should be adequately preserved with nonionic antimicrobial preservatives. The use of preservatives is generally limited to products that are not intended for parenteral use. Intravenous injectable... 

Large-volume parenterals (LVPs) and small-volume parenterals (SVPs) containing no antimicrobial agent should be terminally sterilized. It is common practice to include an antimicrobial agent in SVPs that cannot be terminally sterilized or are intended for multiple-dose use. The general exceptions are products that pass the USP Antimicrobial Preservative Effectiveness Test [1] because of the antimicrobial activity of the active... 

Aqueous products that are at greatest risk from microbial spoilage include solutions, suspensions, and emulsions for repeated oral, parenteral, or external use and include critical products such as multidose injections and eye drops. Unpreserved products without adequate antimicrobial efficacy should not be presented in containers intended for use on more than one occasion unless justified. When antimicrobial preservatives are used, their efficacy has to be demonstrated using the Ph Eur test for antimicrobial preservative efficacy. Factors to be taken into account in designing a preserved product include the nature of the preservative, its concentration in the product, the... 

Perioperative parenteral antibiotics yes with appropriate aerobic and anaerobic antimicrobial coverage with a single dose within 30 min of incision yes with appropriate aerobic and anaerobic antimicrobial coverage with a single dose within 30 min of incision... 

Perioperative parenteral antibiotics parenteral antibiotics with appropriate aerobic/anaerobic antimicrobial coverage should be administered preoperatively, intraoperatively and postoperatively depending upon the length of surgery, operative findings and clinical course... 

Table 5. Parenterally administered antimicrobial agents which can be used alone or combined to provide effective coverage of the mixed aerobic-anaerobic infections arising from human colonic bacteria for patients requiring preventive therapy...

Large doses of parenteral antimicrobials usually are necessary to achieve bactericidal concentrations within vegetations. 

Monotherapy with broad-spectrum parenteral antimicrobials, along with appropriate medical and/or surgical management, is often effective in treating moderate to severe infections (including those in which osteomyelitis is present). 

All preservative systems for both parenteral and nonsterile dosage forms should meet the 3 log reduction at 14 days for bacteria, that is, USP category I requirements. Both EP and BP Antimicrobial Effectiveness Testing would be run only if specially requested by the marketing group. 

The IM and SC routes are by far the most frequently used extravascular parenteral routes of drug administration in farm animals. The less frequently used parenteral routes have limited application, in that they aim at directly placing high concentrations of antimicrobial agent close to the site of infection. These routes of administration include intra-articular or subconjuctival injection and intra-mammary or intra-uterine infusion. These local routes differ from the major parenteral routes in that absorption into the systemic circulation is not a prerequisite for delivery of drug to the site of action. The combined use of systemic and local delivery of drug to the site of infection represents the optimum approach to... 

Age or body weight can affect the systemic availability of many antimicrobial agents. In the physically smaller animal (sheep and pig) the peak serum concentration of a drug is usually higher and is followed by a rapid decline compared with a lower peak and a slower decline of the antibiotic in seruon of the larger animal (cow and horse). The limited experimental data appear to indicate that the extent of systemic availability of IM-administored antibiotics can vary as widely between different sites as between IM and SC sites. A corollary to this observation is that the location of the extra-vascular injection site should be well-defined when determining the systemic availability of parenteral preparations (9). 

Sporadic clinical reports, without the support of data from controlled studies, repeatedly indicate the effectiveness of intratracheal administration of parenteral antimicrobial preparations in the treatment of tracheobronchitis and pneumonia in cattle. The expectation when using this route of administration is that a greater therapeutic effect will be achieved when the drug is placed as close to the infection site as possible, rather than relying on the systemic circulation for drug delivery. 

Parenteral Serious or severe infections not treatable with other antimicrobials, including the penicillins and cephalosporins. 

Drugs given into the rectum are usually wrapped up in some slow delivery matrix so that they are absorbed slowly. An exception is the antimicrobial metronidazole, which can be given through the rectum to achieve as high plasma concentrations as can be achieved with oral or even parenteral administration. 

For parenteral therapy, nafciUin and oxacillin offer comparable efficacy and antimicrobial spectra of activity. Although both drugs undergo hepatic metabolism, only nafcillin requires dose adjustment in patients with combined hepatic and renal insufficiency. Other pharmacokinetic data for nafcillin and oxacillin appear in Table 45.1. Indications for nafcillin or oxacillin include severe staphylococcal infections like cellulitis, empyema, endocarditis, osteomyelitis, pneumonia, septic arthritis, and toxic shock syndrome. 

Many antimicrobial agents have similar pharmacokinetic properties when given orally or parenterally (ie, tetracyclines, trimethoprim-sulfamethoxazole, quinolones, chloramphenicol, metronidazole, clindamycin, rifampin, linezolid and fluconazole). In most cases, oral therapy with these drugs is equally effective, is less costly, and results in fewer complications than parenteral therapy. 

Another important component of most vaccine formulations is a suitable preservative. The three most commonly used preservatives in available vaccines are phenol, 2-phenoxyethanol, and ethyl mercurithiosalicylate (thimerosal). Thimerosal, in particular, is used in multidose vials as an antimicrobial preservative. Concerns about the presence of mercury in thimerosal (25 pg/dose) has led to FDA stopping the use of this preservative in all vaccines by an amendment to the FDA Modernization Act of 1997. By 2001, thimerosal was removed from most childhood vaccines as a precautionary measure. The sources of all of the preservatives for vaccines are the same suppliers that supply preservatives for the parenteral dosage forms (J. T. Baker, Aldrich, Spectrum, etc. from U.S.A.). Table 2 lists some of the preservative concentrations in common vaccines. 

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