Amoxicillin for stomach flu

Production of stably derepressed mutants is a concern during therapy with beta-lactam agents that are weak inducers of beta-lactamase production, such as extended-spectrum and third generation cephalosporins.

These mutants produce increased quantities of beta-lactamases (hyperproduction) despite removal of the inducible antibiotic.

This is most likely to occur

with

The only effective beta-lactam would be a carbapenem, as Class I beta-lactamases can hydrolyze all other types of beta-lactams agents. Extended-spectrum beta-lactamases (ESBLs) are plasmid mediated with a wide substrate profile.

These enzymes are a relatively recent problem, affecting some strains ofВ Klebsiella sp. The emergence of ESBL-producing organisms has been linked with the widespread use of extended-spectrum cephalosporins (154,190).

A carbapenem is a drug of choice against these organisms, while beta-lactamase inhibitor combinations may also be effective (93). It is easier for penicillins to acetylate the PBPs in gram-positive bacteria because these

bacteria

Gram-negative bacteria, however, have an outer membrane composed of a lipopolysaccharide and phospholipid bilayer and between the layers is a periplasmic space. Another space separates the inner membrane with the cytoplasmic membrane. PBPs are located in the cytoplasmic membrane and are protected by beta-lactamases. In the outer membrane there are proteins, known as porins, which act as channels for nutrients and waste products into and out of the bacteria. Penicillins may enter amoxicillin for throat pain the gram-negative bacteria by this route.

Porin permeability to penicillins depends upon size of the molecule, hydrophilicity, and electrical charge (267).

Decreases in the number of porin

channels

Most research has been conducted with the outer-membrane proteins (Omp) ofВ E. Omp F and Omp C are the two main porins, with Omp F being most permeable to beta-lactam agents.

Some mutants which lack Omp F porins can be resistant to beta-lactams due to decreased and slower penetration through the remaining porins (Omp C) and subsequent increased beta-lactamase degradation (66).

Binding to the PBP is necessary for the penicillin to exert its antibacterial effect.

There are natural differences in the affinity for penicillin to a PBP.

For instance, the affinity of the Enterococcal PBP to the antistaphylococcal penicillins is very low versus a high affinity to penicillin G or ampicillin.

This accounts for the resistance seen in the case of oxacillin and Enterococcus. Mutations can occur which can result in changes in susceptibility of an organism, which is “normally” susceptible to a particular penicillin, usually by producing PBPs with a decreased affinity to the penicillin.

An alteration in PBP2 byВ Staphylococcus В to PBP2a results in methicillin resistance, as PBP2a exhibits a decreased affinity for methicillin and most other beta-lactam agents (102).

WithВ Staphylococcus aureus В (241) this type of production of PBPs with decreased affinity for the penicillin is inducible by exposure to the agent, resulting in decreased susceptibility to clamoxyl amoxicillin low concentrations of the drug. An important example of bacteria that can develop such mutations that confer resistance isВ Streptococcus pneumoniae В that is penicillin-resistant.

The resistance mutation is genetically coded with "mosaics" that are made up of native pneumococcal DNA and DNA that is presumably from another streptococcal species, such as viridans streptococci, more resistant to penicillin (93,127).

The genes that appear to be most affected are PBP 2b and 2x.

The current interpretive MIC breakpoints for penicillin as determined by the National Committee for Clinical Laboratory Standards (NCCLS) are 48 hours is an indication for repeat desensitization (210). Cross-Reactivity with Other Beta-Lactams and Related Compounds.

There is a concern over the potential for allergy to other beta-lactam compounds, such as cephalosporins, aztreonam, and the carbapenems, in patients allergic to penicillin. Estimates of cross-reactivity with cephalosporins range from 2-10% (182,В 195), though there is data to suggest that the incidence is much lower (6).

No major or minor determinants exist with cephalosporins, which could account for the low cross-reaction potential.

Cross reaction with the carbapenems may also occur, however the monobactams (aztreonam) appear the have a low propensity for eliciting an immune response and have not shown a cross-reaction with penicillin antibodies when testedВ in vitro В (1).

The bulky side chain, rather than the beta-lactam ring may be the site of immunologic reactivity.

TheВ in vitro В studies (1,В 201) also demonstrated that cross-reaction between aztreonam and ceftazidime occurred, which is expected since the two compounds have identical side chains. Though the risk of cross-reactivity appears to be low, in patients with a history of severe allergy it may be prudent to avoid the use of cephalosporins as good therapeutic alternatives are available. The potential for a cross-reaction with penicillamine has also been explored, as penicillamine is a metabolite of penicillin degradation. A study examined 40 patients with a positive history of penicillin allergy.

Sixteen patients skin tested positive for sensitivity to penicillin only and 1 patient had a positive penicillamine skin test (21).

This data suggests that the incidence of cross-reaction is low, but that penicillamine should be administered with caution to these patients. The penicillins are associated with several adverse effects. These adverse effects will be discussed according to

body

Antibiotic-associated pseudomembranous colitis caused byВ Clostridium difficile , may occur during or immediately after therapy with a penicillin due to changes in normal bowel flora from the broad spectrum coverage and overgrowth of this organism. WhileВ Clostridium difficile В is “sensitive” to ampicillin and amoxicillin, it produces spore form, which survives. In the scenario of diarrhea associated with presence ofВ Clostridium difficile В and depending upon the severity of illness, appropriate treatment with metronidazole or oral vancomycin should be considered. Rash may occur with administration of any penicillin. Patients are over twice as likely to develop a rash while receiving ampicillin or amoxicillin (5-10%) versus the other penicillins (2%) (138).

The ampicillin rash is amoxicillin for dry cough maculopapular and is often self-limited. Patients who have infectious mononucleosis, cytomegalovirus infection, chronic lymphocytic leukemia, or are on concurrent allopurinol are at increased risk of development of such a rash.

Neutropenia can occur with administration of any penicillin at an estimated incidence of 3-8%.

Risk factors include high doses for a prolonged (> 10 day) period of time (166,В 176) and hepatic impairment (212). The mechanism may be due to immune complex deposition on the neutrophil cell membranes (198).

Patients should be monitored for this adverse effect if prolonged treatment courses are used. Inhibition of platelet aggregation can occur due to alterations in adenosine diphosphate responses, particularly with ticarcillin and carbenicillin. Prolonged bleeding times can result, along with actual bleeding (2,В 4,В 82,В 226).

Patients with thrombocytopenia and/or azotemia appear to be at increased risk.

Increased bleeding times were seen in a study of 156 patients receiving ticarcillin (73%), piperacillin (43%), mezlocillin (25%), or cefotaxime (17%). Though some patients were receiving chemotherapy, which could confound results, the trend remained after those patients were removed from the analysis.