Potassium clavulanate uses

It was then assumed that bacterial eradication from the pharynx was the necessary step in prevention of ARF.

As a result, penicillins as a class were assumed to be efficacious in preventing ARF. No study has investigated the efficacy of other antibiotics in prevention of ARF.

Patients who develop ARF require continuous prophylaxis to prevent intercurrent and recurrent streptococcal infections and recurrent episodes of ARF. The preferred regimen consists of penicillin G benzathine, 1.2 million units given intramuscularly every 4 weeks (17). The recurrence rate of ARF with this regimen was reported to be 0.4 cases per 100 patient years of observation (8).

Alternative therapies include oral sulfadiazine (1 g/day for persons over 60 lb and 0.5 g/day for those weighing less than 60 lb) or penicillin V (250 mg, twice a day). Both of these regimens are considered less effective than penicillin G benzathine. This is thought to be due to lack of patient compliance with an oral regimen. Patients who are allergic to penicillin can be treated with erythromycin stearate (250 mg, twice a day) (8). Considerable debate has arisen over the optimal duration of prophylaxis.

Some investigators previously recommended lifelong prophylaxis. However, the risk of recurrence of ARF decreases with patient age and the number of years since the last attack and increases with the presence of rheumatic heart

disease

In 1995, the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the

American

last

Patients who had rheumatic fever with carditis but no valvular disease should receive prophylaxis until adulthood and until at least 10 years had passed since their last attack of ARF. Patients with valvular disease should receive prophylaxis until age 40 and until at least 10 years had passed since their last attack (20). Patients with residual rheumatic valvular disease must receive antibiotic prophylaxis whenever they undergo a surgical or dental

procedure

A cute Glomerulonephritis: Unlike rheumatic fever, post-streptococcal acute glomerulonephritis (AGN) has shown no increase in incidence.

Indeed, nephritogenic strains (particularly serotype M type 12) have decreased in prevalence (54). Treatment strategies in the approach to post-streptococcal acute glomerulonephritis are directed toward management of acute problems. All patients should be treated with penicillin to eradicate the nephritogenic strain regardless of culture results of group A streptococci or immunologic tests.

Paralleling the recent changes in the pathogenesis of ARF, a substantial number of patients who develop post-streptococcal AGN do not have a history of a preceding pharyngitis or soft tissue infection. Penicillin-allergic patients can be treated with erythromycin in doses adequate for treatment of streptococcal pharyngitis.

It is generally recommended that family members be cultured for group A streptococcus.

Family members with positive cultures should be treated appropriately.

Treatment of patients with post-streptococcal AGN or of family contacts is for epidemiologic purposes only.

Therapy will not alter pre-existent post-streptococcal AGN or prevent the disease in patients who are in the latent period.

Some data suggest that antibiotic therapy may have a small effect on prevention of post-streptococcal AGN, but this has not been substantiated.

However, antibiotic therapy is effective in epidemiologic efforts at eradicating nephritogenic strains of group A streptococcus. In high risk settings during an acute epidemic of AGN, universal penicillin prophylaxis can be considered. Recurrent episodes of AGN are rare, and continuous anti-streptococcal prophylaxis is generally not recommended. Long-term prognosis is generally thought to be excellent, but some studies found that up to 20% of patients develop urinary abnormalities (13).

In general, combination antimicrobial therapy offers no added benefit in the treatment of known GAS infections.

Antimicrobial agents possess sufficient activity in vitro to GAS and, when initiated promptly, are effective in the treatment of such infections. However, in clinical situations in which GAS is suspected but has not been identified (e.g., necrotizing fasciitis and TSS) antimicrobial therapy should be initiated with combinations effective against all possible pathogens. Invasive Streptococcal Infections: For necrotizing streptococcal infections, early and aggressive surgical debridement of the site of infection as well as appropriate antimicrobial therapy is required.

The patient with StrepTSS also requires intensive management of hemodynamic abnormalities and vital functions. Some investigators have suggested use of hyperbaric oxygen therapy (HBO) in treatment of necrotizing fasciitis (reviewed in (7)), however, HBO therapy is not without risks, and its use has not been well studied. Other proposed therapeutic interventions include the use of intravenous immunoglobulin (IVIG) and monoclonal antibodies. It is thought that IVIG may act by binding and inactivating toxins (3); however, use of IVIG in the treatment of StrepTSS has not been

thoroughly

Investigators are studying the use of monoclonal antibodies against specific group A streptococcal toxins and the neutralization of circulating cytokines in managing invasive streptococcal disease caused by toxin-producing strains.

It was recently suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDS) in the treatment of fever in patients with GAS infections may predispose the patient to a more severe invasive infection.

NSAIDs may inhibit neutrophil function and enhance cytokine production (79).

In addition, their use may mask some of the early signs and symptoms of invasive GAS infections and has been associated with episodes of necrotizing fasciitis and toxic shock syndrome in patients with varicella (79).

P haryngitis : Tonsillectomy may help reduce the number of acute infections in children with recurrent GAS pharyngitis and is generally recommended for children who have 6 to 7 documented GAS infections in a given year or 3 to 4 infections in each of 2 years (8).

It may also be desirable as a method to eliminate the carrier state in a select group of patients such as those with a family history of rheumatic fever.

Other alternative therapies that have been suggested to reduce the incidence of treatment failures in GAS pharyngitis include using ?-streptococci to replace normal pharyngeal flora, delaying treatment of GAS pharyngitis 48 h to promote the host's immune system (discussed above), and using topical antibiotics.

Elimination of ?-streptococci from the pharynx after therapy for acute GAS pharyngitis has been proposed as a possible explanation for treatment failures, development of the carrier phenomenon, and frequent recurrences (76). ?-Streptococci interfere strongly against GAS (73).

?-Streptococci share pharyngeal epithelial receptor sites in the posterior pharynx with GAS, and elimination of ?-streptococci may provide

more

None of the patients treated with ?-streptococci had a recurrence of GAS pharyngitis over a period of 3 months, while the control group had an 8% recurrence rate (73). A cute Rheumatic Fever: Salicylates and steroids are very effective in suppressing the acute manifestations of rheumatic fever, but neither has been shown to proven chronic valvular rheumatic heart disease (55). Patients with definite clinical evidence of arthritis should receive aspirin starting at a total dose of 100 mg/kg/day in divided doses for the first two

weeks

Corticosteroid therapy is only for patients with significant carditis, amoxicillin and clavulanate potassium 625mg especially cardiomegaly or congestive heart failure.

Prednisone is the drug of choice, starting at 2 mg/kg/day in

divided

After 2 - 3 weeks, a slow taper may begin, decreasing the daily dose at the rate of 5 mg every 2 - 3 days.

When tapering is started, aspirin at 75 mg/kg/day should be added and continued for 6 weeks after prednisone is stopped (55).

The problem of bacteriologic and clinical failures in the treatment of GAS pharyngitis has led some investigators to suggest that all patients should receive a test of cure at the end of treatment.

The patient who is symptomatic and culture positive at the end of treatment for acute pharyngitis may represent either failed treatment or acquisition of a new strain of GAS and should receive further treatment.

Clearly, patients with previous rheumatic fever who have symptoms of strep throat should be re-cultured at the end of treatment.

Development of an effective group A streptococcal vaccine continues to be of interest; currently, none are commercially available. Researchers have looked at the conserved region of the M protein since this region is shared by all serotypes of GAS and because long-term exposure to group A streptococci results in acquired immunity (29). A vaccine incorporating the conserved region of the M protein of group A streptococcus may stimulate a rapid rise in protective antibodies, but may also stimulate development of cross-reactive antibodies that recognize heart tissue.

Because of these potential safety issues, recent efforts have been directed at developing a vaccine against certain epitopes of the M protein that do not cross-react with myocardial tissue, providing a safer vaccine for immunizations (22). To provide immunity against the 150 or so known M-types of GAS, the vaccine would

need

Group A streptococci are highly contagious and epidemics of pharyngitis, impetigo, scarlet fever, rheumatic fever, post-streptococcal glomerulonephritis, bacteremia, puerperal sepsis, streptococcal toxic shock syndrome and necrotizing fasciitis have been described (reviewed in (82)).

The acquisition of GAS in the family environment poses problems for individuals in that environment who may have previously acquired rheumatic fever. In the hospital environment, group A streptococcus can spread rapidly to patients with surgical wounds, burns or chicken pox or post-partum patients.

Strict adherence to infection control measures is crucial.

Because there are over 150 different M-types of GAS this means that nosocomial isolates should be saved for subsequent epidemiologic comparisons should additional cases be identified. Performing M-typing or comparing RFLP patterns is extremely important to determine if these cases originated from a common source such as an employee who is a carrier of GAS. Strict isolation procedures should be employed in patients who are admitted to hospitals with GAS infections. Close contacts of primary cases of severe invasive GAS infections are at greater risk than the general population for development of colonization or superficial infection. The risk for invasive infection is less, but still higher than the general population. The clinician

managing

In a situation such as military barracks, benzathine penicillin administered intramuscularly on a monthly basis has been very useful to prevent streptococcal pharyngitis and rheumatic fever. Group A streptococcus has the unique ability to cause both acute purulent infections and nonpurulent complications that develop days after an initial infection. With a recognized increase in incidence and severity of invasive group A streptococcal infections and changes in the epidemiology of ARF, treatment of group A streptococcal infections has taken on even greater importance. While penicillin remains the mainstay of treatment, its use has recently been brought into question.

New antibiotics and new strategies for treatment are being evaluated, and a vaccine effective against group A streptococcus is being developed. Once thought to have been relegated to simple sore throats, group A streptococcus has returned to the forefront of infectious diseases.

In Vitro Susceptibilities of Streptococcus pyogenes to Common Antibiotics.

Bone Penetration of Amoxicillin and Clavulanic Acid Evaluated by Population Pharmacokinetics and Monte Carlo Simulation. Find this author on Google Scholar Find this author on PubMed Search for this author on this site. Find this author on Google Scholar Find this author on PubMed Search for this author on this site.

Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: ibmp@osn.de. Amoxicillin (amoxicilline)-clavulanic acid has promising activity against pathogens that cause bone infections.

We present the first evaluation of the bone penetration of a beta-lactam by population pharmacokinetics and pharmacodynamic profiling via Monte Carlo simulations. Twenty uninfected patients undergoing total hip replacement received a single intravenous infusion of 2,000 mg/200 mg amoxicillin-clavulanic acid before surgery. Bone samples were pulverized under liquid nitrogen with a cryogenic mill, including an internal standard.

The drug concentrations in serum and total bone were analyzed by liquid chromatography-tandem mass spectrometry. We used NONMEM and S-ADAPT for population pharmacokinetic analysis and a target time of the non-protein-bound drug concentration above the MIC for ?50% of the dosing interval for near-maximal bactericidal activity in serum. The median of the

ratio

For a 30-min infusion of 2,000 mg/200 mg amoxicillin-clavulanic acid every 4 h, amoxicillin achieved robust (?90%) probabilities of target attainment (PTAs) for MICs of ?12 mg/liter in serum and 2 to 3 mg/liter in bone and population PTAs above 95% against methicillin-susceptible Staphylococcus aureus in bone and serum. The AUC of amoxicillin-clavulanic acid was 5 to 10 times lower in bone than in serum, and amoxicillin-clavulanic acid achieved a rapid equilibrium and favorable population PTAs against pathogens commonly encountered in bone infections. Osteomyelitis is difficult to diagnose and treat and may cause irreversible damage. Antibiotic treatment over weeks to months is required, often in addition to surgical debridement.

To reduce the incidence of infections after orthopedic surgery, perioperative prophylaxis is standard practice.

Each year more than a million hip replacements are done worldwide.

Prosthetic devices are particularly susceptible to infections, more than 50% of which are due to Staphylococcus aureus or coagulase-negative staphylococci, such as S.

It is vitally important that adequate surgical prophylaxis be used and that sufficient concentrations of antibiotic with activity against frequently encountered

pathogens

Amoxicillin (amoxicilline) in combination with clavulanic acid is active against pathogens commonly found in prosthesis-related bone infections (MICs at which 90% of bacteria are inhibited [MIC 90 s], 1 mg/liter for methicillin-susceptible S. Successful treatment of infections with amoxicillin-clavulanic acid after molar extraction (22), peri-implantitis (52), osteomyelitis due to diabetic foot infections (40), prophylaxis of infections after orthognathic surgery (6), and staphylococcal osteomyelitis in a rat model (23) has been reported.