Penicillin vk what does v stand for

A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions. Penicillin V works by stopping the bacteria from multiplying. Syphilis : Penicillin is the preferred treatment for syphilis. Early treatment is crucial to prevent the bacteria from spreading to and damaging other organs.

Genital herpes : Once you are infected with genital herpes, the virus remains in your body for life. Amoxicillin is usually the first choice for tooth infection treatment. Clavulanate is a drug that makes amoxicillin even more effective when the two are combined.

So, if it appears that your tooth infection is more serious, your dentist may prescribe amoxicillin with clavulanate instead of plain amoxicillin. Medications like antibiotics can also cause your pee to smell, because those that contain penicillin are derived from mold. That can give your urine a yeasty or fungus-like funk, but it should dissipate once you run through your antibiotic course.

Adults and teenagers— to milligrams mg every six to eight hours. Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 2. Antibiotics begin to work right after you start taking them.

However, you might not feel better for two to three days. How quickly you get better after antibiotic treatment varies. Penicillin is considered a narrow-spectrum antibiotic because it is mainly effective against gram-positive aerobic organisms such as: Streptococcus pneumoniae.

Is Penicillin VK the same as amoxicillin? How long is Penicillin VK good for? How long does Penicillin VK stay in your system? What type of infections does Penicillin VK treat? Can penicillin VK make you tired? Can you overdose on penicillin VK?

What is penicillin VK mg used to treat? What is Penicillin VK mg used for? Is Phenoxymethylpenicillin stronger than amoxicillin? Is Penicillin an antimicrobial drug? What is a natural penicillin? Natural Penicillins.

Is Penicillin good for tooth infection? Can you buy penicillin over the counter? Why is it called penicillin V? What type of bacteria is penicillin most effective against?

What is procaine penicillin G used for? Take penicillin V potassium exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The recommended dose range for penicillin V potassium is mg to mg given several times a day. The frequency will depend on what kind of infection is being treated.

If you take too much penicillin V potassium, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away. Penicillin VK. Penicillin VK is an antibiotic and treats infection. Finish taking all of your medication.

Even if you feel better, do not stop taking medication unless your doctor tells you to stop. Updated: November 7, How was your experience with Phenoxymethylpenicillin? First, a little about yourself Male Female. What tips would you provide a friend before taking Phenoxymethylpenicillin? Choose one. Back Next. How well did Phenoxymethylpenicillin work for you?

Did you experience many side effects while taking this drug? How likely would you be to recommend Phenoxymethylpenicillin to a friend? Back Submit. By , benzylpenicillin could be produced in sufficient quantity to treat several infected patients. Clinical trials with the agent, conducted by Florey and colleagues, were successful and during World War II, benzylpenicillin was used to treat patients with streptococcal, gonococcal, and treponemal infections.

Shortages of the agent continued until the late s when production of large amounts of drug became possible by a deep-fermentation procedure Since then, many synthetic penicillins have been developed, but resistance to the agents has increased.

Despite the emergence of resistance to penicillins and the development of other classes of anti-infective agents, the penicillins remain one of the most important anti-infective classes of drugs well into the nineties. In fact, penicillin G is still the drug of choice for many types of infections, including syphilis and certain types of endocarditis. The basic chemical structure of all penicillins consists of a beta-lactam ring, a thiazolidine ring, and a side chain 6-aminopenicillanic acid.

The antibacterial activity of the penicillins lies within the beta-lactam ring. Any alteration in this ring structure forms penicilloic acid and the antibacterial activity of the compound is lost. The side chain varies with each penicillin compound and generally determines the spectrum of activity, as well as the pharmacokinetic properties of the compound.

There are several natural penicillins penicillin dihydro F, X, and K , of which benzylpenicillin penicillin G is the most active and is the only natural penicillin used clinically Manipulations of the side chain have produced compounds that are stable against certain bacteria, such as Staphylococcus aureus , which produce beta-lactamase enzymes penicillinase.

The side chain sterically inhibits the beta-lactamase hydrolysis of the beta-lactam ring. Other penicillin compounds have side chains, which are stable against beta-lactamases produced by gram-negative rods.

Side chain changes can also increase the bacterial permeability of the compound and can result in increased oral absorption from the intestinal tract by rendering oral agents more stable to gastric acid breakdown , The penicillin compounds can be divided into categories based upon their spectrum of activity Table 1.

Penicillin G is a natural penicillin that is produced directly from fermentation of Penicillium crysogenum. Penicillin V is a derivative of penicillin G and because of similarities in spectrum of activity, is considered a natural penicillin.

The natural penicillins have activity against non-beta-lactamase producing gram-positive cocci, including viridans streptococci, group A streptococci, Streptococcus pneumoniae , and anaerobic streptococcus Peptostreptococcus , Peptococcus sp. Enterococcus sp. The natural penicillins have activity against Clostridium sp. Activity against gram-negative cocci is limited and includes Neisseria meningitidis , non- penicillinase producing Neisseria gonorrheae , and Pasteurella multocida.

Similar to staphylococcal infection, natural penicillins should not be used for treatment of gonorrhea due to the increased potential of a resistant organism and subsequent treatment failure. The anaerobic coverage of penicillin V is less than that of penicillin G.

Natural penicillins also have excellent activity against the spirochete, Treponema pallidum , the causative organism of syphilis. The agents in this group are also known as the antistaphylococcal penicillins. The addition of an isoxazolyl side chain to the penicillin compound protects the beta-lactam ring from acid hydrolysis by penicillinases produced by Staphylococcus sp.

Methicillin, the first agent synthesized in this group, is rarely used currently due to a higher incidence of occurrence of interstitial nephritis and is no longer commercially available in the United States. Nafcillin and oxacillin are the agents commonly used parenterally, while dicloxacillin is available for oral use. These agents have activity against Staphylococcus sp including penicillinase-producing strains.

Strains of methicillin-resistant Staphylococcus aureus MRSA and methicillin-resistant Staphylococcus epidermidis MRSE exist and can be the prevalent Staphylococcal organism in certain areas, such as certain hospitals or wards within the hospital. These organisms are not sensitive to the penicillinase-resistant penicillins. While less active against streptococcal sp. Clinically, in serious, life-threatening infections where a gram-positive organism is suspected, combinations of penicillin G plus a penicillinase-resistant penicillin can be utilized to achieve maximal streptococcal and staphylococcal coverage.

A notable exception to the gram-positive coverage of this class of penicillins is the Enterococci. These organisms are not susceptible to this class of penicillins. Anaerobic activity ranges from minimal to none and gram-negative activity is virtually nonexistent. Because of the need for improved coverage against gram-negative organisms, further manipulation of the side chain was conducted. By adding an amino group to the basic penicillin compound, the aminopenicillins were developed.

The spectrum of activity against gram-positive organisms is similar to that of the natural penicillins. These agents retain activity against streptococcal sp. The added side chain does not, however, inhibit hydrolysis by Staphylococcal penicillinases or gram-negative beta-lactamases.

The enhanced spectrum of these drugs includes activity against gram-negative bacilli, including H. These drugs were developed in the s and were, at that time, very effective against these organisms.

Presently, however, many strains of these gram-negative organisms are resistant to ampicillin. Combinations of an aminopenicillin plus a beta-lactamase inhibitor, such as clavulanic acid or sulbactam, are useful for treatment of infections caused by beta-lactamase producing organisms. A carboxyl group substitution in place of the amino group yields penicillin compounds that have a greater gram-negative spectrum of action, including activity against Pseudomonas aeruginosa , most likely due to increased bacterial penetration through the cell wall.

Carbenicillin and ticarcillin are the two drugs in this class. Their spectrum of activity includes that of ampicillin, while also encompassing Enterobacter , Providencia , Morganella , indole-positive Proteus , and Pseudomonas aeruginosa , with ticarcillin having slightly greater activity against Pseudomonas aeruginosa versus carbenicillin Coverage against Klebsiella and Serratia are less predictable and, unlike ampicillin, these compounds have little activity against Enterococcus.

These agents are not effective against beta-lactamase producing organisms unless combined with a beta-lactamase inhibitor e. In order to increase gram-negative coverage and particularly coverage against Pseudomonas aeruginosa , a ureido group addition to the penicillin structure produces the compounds azlocillin and mezlocillin. A ureido group plus a piperazine side chain produces piperacillin.

The gram-negative coverage of this class of penicillins includes that of the carboxypenicillins, plus coverage against Klebsiella , Serratia , Enterobacter , Enterococcus , and increased anaerobic coverage The activity against Streptococci is slightly less that of the natural penicillins and ampicillin. Of the drugs in this class, piperacillin has the most activity against Pseudomonas aeruginosa 52 , As with the carboxypenicillins, drugs in this class are susceptible to inactivation by bacterial beta-lactamase production, unless combined with a beta-lactamase inhibitor e.

When choosing an antimicrobial agent and designing appropriate dosing regimens for the drug, it is important to consider spectrum of activity, but also incorporate known pharmacodynamic principles about the drug. In this manner, efficacy can potentially be maximized while toxicity can be minimized. Some excellent reviews on these concepts have been published 71 , All beta-lactam drugs including the penicillins exert relatively concentration-independent bactericidal activity, meaning that the concentration of drug does not appreciably affect its ability to exert an antibacterial effect 25 , However, once the drug concentration falls below the level of the MIC and the PAE has ceased, the kill rate diminishes.

This effect, however, does not appear to be clinically significant, as there is very limited data to support decreased bactericidal activity in vivo due to high serum concentrations. Another factor that may influence bactericidal activity is bacterial inoculum size. Generally, the more dense the bacterial population i. This may be the case with nosocomial gram-negative pneumonias or other serious infections. Treatment with a penicillin as monotherapy may result in a relapse after completion of therapy when the resistant sub-variants are no longer suppressed and begin to regrow.

This scenario is not unique to the penicillins, and in fact may occur with other antibiotics when used as monotherapy. The bactericidal activity of the penicillins does not appear to be affected by changes in pH or oxygen tension. The location of the organism is important, however, as in vitro efficacy may not correspond to in vivo efficacy.

Penicillins and other beta-lactams do not penetrate well into phagocytes , thus limiting their ability to kill intracellular pathogens. In addition, penicillins only exert their bactericidal effect on bacteria that are actively replicating. Combinations of a beta-lactam plus another agent, such as an aminoglycoside, kill some organisms most effectively. In these cases, antibacterial synergy occurs.

Synergy is defined as an effect, such as bactericidal activity, that is significantly greater with the combination than the sum of the two agents when used alone. The mechanism of this effect with penicillins and aminoglycosides may be due to cell wall disruption by the penicillin, facilitating increased entry of the aminoglycoside into the bacteria Enterococcal endocarditis is such an example, as penicillin monotherapy results in bacteriostatic activity and very high relapse rates after treatment , while the combination of penicillin plus an aminoglycoside is bactericidal Other organisms for which synergy seems to be important with regard to the penicillins includes Pseudomonas aeruginosa.

Again, a combination of an antipseudomonal penicillin plus an aminoglycoside may result in increased bactericidal activity. This has been demonstrated in vitro and animal studies 5 , 77 , , but there is limited data in humans to support these findings.

In vitro synergy between the extended spectrum penicillins azlocillin, mezlocillin and ciprofloxacin has also been demonstrated , , Immunocompromised patients are a population who may benefit the most from antipseudomonal synergy.

There is data to suggest that synergistic combination therapy results in increased survival versus non-synergistic combinations of drugs , , Antibacterial antagonism is defined as a resulting effect that is significantly less in combination than with either of the two drugs when used as monotherapy. This effect has been demonstrated with the penicillins in combination with chlortetracycline in patients with pneumococcal meningitis, when penicillin monotherapy was more effective that the combination of agents Combinations of penicillin plus chloramphenicol have demonstrated in vitro antagonism against pneumococci , however, clinically this may be of little importance since the combination only diminished penicillins bactericidal activity resulting in bacteriostatic activity and chloramphenicol retains its antibacterial effect.

Also, the use of chloramphenicol has decreased dramatically in the last decade due to the availability of newer agents that are equally efficacious and less toxic. Antagonism can also occur due to a physical incompatibility with inactivation between two drugs when infused together. This can occur with carbenicillin or ticarcillin with an aminoglycoside.

These drugs should therefore not be mixed in the same infusion. The PAE is defined as a persistent suppression of bacterial growth after effective exposure to an antimicrobial agent when serum concentrations of the drug have fallen to levels below the MIC. This effect differs between infecting organisms and between drugs. The mechanism of the PAE is not entirely clear, but may be due to persistent binding of the penicillin to penicillin-binding proteins PBPs and the time that is necessary for the organism to resynthesize new PBPs The PAE was first noted with penicillin G and Staphylococcus aureus , when it was noted that there was a short period of time where bacterial regrowth did not occur after exposure to the drug.

Subsequently, this phenomenon has been described with the penicillins for other gram-positive organisms 42 , , including Streptococcus pneumoniae and Enterococcus faecalis. The length of the PAE can range from hours Table 4 , depending upon the penicillin. As stated previously, the type of organism can affect the PAE.

The penicillins do not exhibit an appreciable PAE against gram-negative organisms. Also, combinations of antimicrobial agents can result in a synergistic PAE.

Combinations of penicillins plus various aminoglycosides have resulted in synergistic or additive PAEs for Enterococcus faecalis and Enterococcus faecium 86 , , along with Staphylococcus aureus A number of studies of beta-lactam agents demonstrated that increased half-life and not peak concentration influenced bactericidal activity 97 , , , This implies that increased duration of drug exposure above the MIC would be more predictive of positive outcome versus increased drug doses and subsequent increased peak concentrations.

In a neutropenic mouse model infected with Pseudomonas aeruginosa , the impact of different dosing intervals of ticarcillin was studied.

Equivalent daily doses were administered every hour or every 3 hours. The mice that received drug every hour a lower dose administered more frequently had a greater antibacterial effect These findings were also supported by studies of Klebsiella pneumoniae pneumonia in rats , in Klebsiella pneumoniae lung and thigh infections in neutropenic mice , Pseudomonas aeruginosa infection in neutropenic rats , Staphylococcus aureus in rats recovering from hemorrhagic shock , and in Enterococcal endocarditis For gram-negative infections, continuous infusion of the penicillin may be most appropriate to maintain serum concentrations above the MIC for the entire dosing interval.

One study examined combinations of carbenicillin plus continuous infusion cefamandole, carbenicillin plus intermittent cefamandole, and carbenicillin plus continuous infusion tobramycin in febrile, neutropenic cancer patients The most effective regimen was the carbenicillin plus continuous infusion cefamandole.

The use of cefuroxime as a single drug in the setting of in vitro resistance was associated with an increase in mortality, but this was not seen with discordant therapy when penicillins, ceftriaxone, or cefotaxime were used. In vitro data support more frequent administration of piperacillin in suppression of microbial growth As previously stated, data in humans comparing continuous infusion with intermittent dosing is limited.

The study by Bodey et al appears to support such dosing, however some small studies did not demonstrate any differences in response rates , The study by Zeisler et al. The advantage of continuous infusion would be the potential maximization of efficacy and potentially decreased costs Disadvantages, however, include patient inconvenience with a continually infusing solution, lack of knowledge about proper dosing, and compatibility issues with other necessary intravenous drugs Many of these concerns may be addressed by educational efforts.

Other concerns include adequate tissue penetration with continuous infusion. Some studies have demonstrated good penetration of continuous infusion beta-lactams into extravascular space , Other data appear to support intermittent injections resulting in increased tissue penetration, as seen in models of rabbit fibrin clots 14 , , however the concentrations achieved with continuous infusion may be adequately above the organism MIC to treat the infection.

Continuous infusion may be most beneficial in patients with impaired host defenses or in life-threatening infections. In these cases, patient convenience is less of an issue and the potential benefit from maximizing efficacy is greatest. Dosing by continuous infusion can be accomplished by use of nomograms or by monitoring a steady-state serum concentration after half-lives or approximately hours into the infusion for most penicillins and adjusting the dose in relation to the serum concentration and the organism MIC.

Penicillins are bactericidal agents that exert their mechanism of action by inhibition of bacterial cell wall synthesis and by inducing a bacterial autolytic effect. Penicillins exert their bactericidal activity primarily by inhibiting bacterial cell wall synthesis. Though the exact mechanism of action is not fully elucidated, it appears that penicillins bind to penicillin-binding proteins PBPs , which are enzymes transpeptidases, carboxypeptidases, and endopeptidases that play an important role in the formation and maintenance of the cell wall structure.

The cell wall is made up of peptidoglycan, or murein sacculus, which is a polymeric component consisting of long polysaccharide chains of N-acetylglucosamine and N-acetylmuramic acid cross-linked by shorter peptide chains.

The formation of peptidoglycan can be divided into three stages, including precursor formation in the cytoplasm, linkage of precursor products into a long polymer, and finally cross-linking by transpeptidation. It is the final transpeptidation process that is inhibited by penicillins by acting as a structural analog of acyl-D-alanyl-D-alanine the substrate of the enzyme and acylating the transpeptidase enzyme. The peptidoglycan structure, and therefore the cell wall structure, is weakened, leading to cell death , , Other mechanisms of cell death are also possible.

Also, there are differences in PBPs between gram-positive and gram-negative bacteria and there are differences in affinity between penicillin compounds to various PBPs. These differences can affect spectrum of activity.

There are several PBPs that the penicillins simultaneously inactivate. Inhibition of certain PBPs may be related to the activation of a bacterial autolytic process by inactivation of endogenous inhibitors of these autolysins or murein hydrolases These enzymes cleave parts of the cell wall to make room for peptidoglycan synthesis for cell wall expansion With inhibition of cell wall synthesis, bacterial lysis can occur due to increased osmotic pressure. This autolysis may be cell cycle dependent, that is, most likely to occur while the cell is dividing These organisms are inhibited, but not killed by penicillins A limitation to the clinical use of penicillins is the emergence of resistant organisms.

Antimicrobial resistance can arise during therapy by selective pressure or can be present due to acquisition of a naturally resistant strain.

A classic example of penicillin resistance is the case of Staphylococcus aureus , which was susceptible to penicillin G when the compound was first discovered around Resistance of other gram-positive and gram-negative organisms also occurs, which can lead to challenges in treatment of active infection.

Resistance rates for different organisms vary according to geographic location and are summarized in Table 5 93 , , , , , Of particular concern in the United States is the emergence of penicillin-resistant and multi-drug resistant pneumococci and methicillin-resistant staphylococci, as treatment options in these scenarios are limited 8 , Inactivation by beta-lactamase enzymes is the most common mechanism of resistance to the beta-lactam agents.

The beta-lactamase reacts with the beta-lactam bond by hydrolysis forming acidic derivatives and subsequent loss of antibacterial activity. There are several classification schemes for the numerous beta-lactamases, including those of Jack and Richmond , Richmond and Sykes , and Bush 44 , The Bush scheme classifies according to substrate preference and susceptibility to clavulanate inhibition. A limitation of these schemes, however, is that they can be confusing due to numerous codes and abbreviations Both gram-positive and gram-negative organisms produce beta-lactamases, mediated either by plasmids or chromosomes.

Gram-positive bacteria that produce beta-lactamases particularly Staphylococcus can transfer resistance through plasmids or transposons. Plasmids are extrachromosomal genetic material that are autonomous, self-reproducing and can be conjugating.

By conjugation, the genetic information is transferred to other Staphylococcus species, including aureus and epidermidis. Transposons are DNA elements that can move from one part of the bacterial chromosome to another. Beta-lactamases of Staphylococcus can be inducible by use of beta-lactam antibiotics, meaning that after exposure to a beta-lactam agent, the organism can greatly increase beta-lactamase production.

The inducible production generally ceases after the beta-lactam is removed As stated previously, gram-negative bacteria secrete beta-lactamases into the periplasmic space and are effective in protecting the PBPs located on the bacterial inner membrane from the antibiotic.

These enzymes can be either chromosomally-encoded or plasmid-encoded They are produced either constitutively production of a constant amount of beta-lactamase regardless of exposure to beta-lactam agents or are inducible and can affect beta-lactam compounds in different ways. Some agents are quickly destroyed, while others are destroyed at a much slower rate and therefore have increased antibacterial activity.

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 chromosomally- mediated Bush Group I enzymes for which the preferred substrate is cephalosporins. Rapid emergence of resistance can occur in this circumstance, particularly in infections caused by Pseudomonas aeruginosa or Enterobacter cloacae 50 , , due to selection of the mutants after the more susceptible organisms are killed during treatment.

In this instance, the mutants can proliferate and can become the predominant infecting organism. 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 of Klebsiella sp. The emergence of ESBL-producing organisms has been linked with the widespread use of extended-spectrum cephalosporins , A carbapenem is a drug of choice against these organisms, while beta-lactamase inhibitor combinations may also be effective Video: Mechanism of Resistance -- Destruction.

It is easier for penicillins to acetylate the PBPs in gram-positive bacteria because these bacteria have only a thick cell wall layer protecting the PBPs on the inner membrane. Gram-negative bacteria, however, have an outer membrane composed of a lipopolysaccharide and phospholipid bilayer and between the layers is a periplasmic space. An inner membrane is composed of peptidoglycan. 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 the gram-negative bacteria by this route. Porin permeability to penicillins depends upon size of the molecule, hydrophilicity, and electrical charge Decreases in the number of porin channels have been reported to be a mechanism of resistance to beta-lactam agents Most research has been conducted with the outer-membrane proteins Omp of E.

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 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. With Staphylococcus aureus this type of production of PBPs with decreased affinity for the penicillin is inducible by exposure to the agent, resulting in decreased susceptibility to low concentrations of the drug. An important example of bacteria that can develop such mutations that confer resistance is Streptococcus pneumoniae 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 , The genes that appear to be most affected are PBP 2b and 2x. Because of resistance, penicillin may not achieve adequate concentrations in the cerebrospinal fluid to treat meningitis if the infecting organism is intermediate or highly resistant to the drug.

The clinical impact of penicillin resistant Streptococcus pneumoniae outside the setting of the central nervous system has been uncertain, however one large prospective study of hospitalized patients with positive blood cultures for Streptococcus pneumoniae examined the impact of resistance, antibiotics administered, and clinical outcome.

Because of concerns over infectious organisms that are emerging resistant to our standard therapies, there is a need for prevention. Infection control practices should be followed, which include hand washing and changing gloves between examination of patients. These methods can limit the dissemination of a resistant organism in a hospital environment Unfortunately, such practices are not routinely followed by health-care providers despite educational efforts 94 , Optimization of antimicrobial use in hospitals is desirable as it is has been demonstrated that use and overuse of broad-spectrum antimicrobials is associated with emergence of resistant organisms 50 , , particularly with ESBL-producing organisms , and it is suspected with penicillin and vancomycin resistant enterococcus.

Antibiotic control programs have been implemented in many institutions with some success 79 , Successful policies, however, can be time and labor intensive and require a full institutional commitment in the form of adequate personnel for implementation and medical staff support for the program.

Pharmacologically, there are strategies to overcome and prevent resistance. The use of combination antimicrobial therapy is a method to provide adequate coverage against suspected organisms There is animal model data to suggest that combination chemotherapy that is synergistic may have a benefit in prevention of emergence of resistance 89 , , however clinical data is limited. The pharmacokinetics of the penicillins varies between compounds.

Absorption between oral agents varies greatly, with amoxicillin and dicloxacillin producing adequate serum concentrations and penicillin G and carbenicillin producing very poor serum concentrations. The penicillins are widely distributed in the body, with adequate levels achieved in serum, tissues, bile, and synovial fluid. Penetration into the cerebrospinal fluid CSF in patients with uninflamed meninges is relatively poor with only 0. The primary route of elimination for most penicillins is renal, with some hepatic metabolism.

Some compounds, however, are primarily eliminated by the hepatic route. The absorption, distribution, metabolism, and excretion will be described for each class of penicillins. Pharmacokinetic properties for the penicillins are summarized in Table 6. Aqueous crystalline penicillin G, or benzylpenicillin, administered intravenously is the most commonly utilized formulation for this class of penicillins. This route of administration is preferred in ill patients due to increased serum concentrations achieved versus oral or intramuscular IM routes of administration with penicillin G or other natural penicillins.

The drug is widely distributed with an apparent volume of distribution Vd of 0. Distribution into the CSF is minimal with uninflamed meninges, but increases with inflammation. There is, however, some hepatic elimination. The pharmacokinetic advantage to this drug is that high serum concentrations are achieved rapidly, but the half-life is approximately 30 minutes, necessitating redoing every hours. The environment of the stomach decreases its absorption due to gastric acid breakdown.

In hypochlorhydric patients, such as the elderly, oral penicillin G has an increased absorption due to an increasing gastric pH. Penicillin V, administered orally, has an increased absorption compared to penicillin G due to its increased acid stability nearly double the peak serum concentrations. Low concentrations are attained in tissues.

Concurrent administration of food can decrease the absorption of the oral natural penicillins, most likely due to binding of the penicillin onto the food particles. Because of poor absorption and limited clinical utility, oral penicillin G is no longer available in the United States.

Procaine penicillin G PPG and benzathine penicillin G BPG are repository forms of penicillin administered intramuscularly IM , with prolonged absorption and subsequent extended serum concentrations of penicillin G. The advantage of these long acting agents is that dosing can be less frequent if the organism is susceptible to the lower levels achieved, such as in the case of BPG and Treponema pallidum , the causative agent of syphilis, where MICs are usually 0.

PPB contains mg procaine with every , units penicillin G. Patients who are hypersensitive to procaine may experience adverse reactions, particularly when high doses e. Methicillin is not orally absorbed and is therefore only given by the intravenous route.

Nafcillin has poor oral absorption and its use is generally limited to intravenous or intramuscular routes. Methicillin is eliminated primarily through the kidney by glomerular filtration or tubular secretion. Oxacillin is both renally eliminated and hepatically metabolized. Nafcillin, however, is primarily hepatically metabolized; therefore a dosage adjustment in renally impaired patients is not necessary. Unlike the natural penicillins, these agents exhibit increased stability to gastric acid hydrolysis.

Because of this difference, oral ampicillin has been favored for treatment of a localized Shigella infection when lack of absorption is desirable. Food delays the absorption of ampicillin and amoxicillin, however the extent of absorption is decreased only for ampicillin. Penetration of ampicillin into the CSF in patients with inflamed meninges occurs with CSF concentrations of approximately 1. Bacampicillin is a prodrug of ampicillin and is hydrolyzed to ampicillin by esterases during absorption and distribution.

The use of this drug, however, has decreased since the availability of orally administered quinolones for these indications. Ticarcillin, mezlocillin, and piperacillin penetrate fairly well into the CSF in patients with inflamed meninges. They also distribute well into bile, with concentrations of piperacillin nearly 50 times higher than that seen in the serum 92 , Penetration into diseased biliary tracts e. Elimination of these compounds is by both renal and nonrenal routes.

Because many of the penicillins are renally excreted, impairment in renal function can result in prolonged half-lives and subsequent increased serum concentrations of drug 18 and can increase the propensity for adverse effects. It is therefore important to adjust doses or dosing intervals for many of the penicillins in these patients Table 7.

Other penicillins, including mezlocillin and piperacillin 24 , 64 should also have their dosing regimen adjusted in renal impairment. With these drugs, however, biliary excretion also occurs, resulting in serum concentrations that are not in proportion to the degree of renal impairment. Oxacillin, cloxacillin, and dicloxacillin, while partially renally excreted, have only moderate increases in half-life 1.

Nafcillin and oxacillin are not appreciably cleared by hemodialysis, so supplemental dosing is not necessary. Peritoneal dialysis does not significantly remove any of the penicillins; therefore supplemental dosing is not necessary. Most penicillins are primarily renally eliminated and do not require a dosage adjustment on hepatic impairment.