Piperacillin + Tazobactam Kabi 4 g + 0.5 g No. 10 bottles

Piperacillin + Tazobactam Kabi 4 g + 0.5 g No. 10 bottles

Content

Indications Dosage regimen Side effects Contraindications for use Use during pregnancy and breastfeeding Use for impaired renal function Use in children Special instructions Drug interactions

Indications

Bacterial infections caused by sensitive microflora in adults and children over 12 years of age: infections of the lower respiratory tract (pneumonia, lung abscess, pleural empyema); abdominal infections (peritonitis, pelvioperitonitis, cholangitis, gallbladder empyema, appendicitis (including complicated by an abscess or perforation)). urinary tract infections, incl. complicated (pyelonephritis, cystitis, prostatitis, epididymitis, gonorrhea, endometritis, vulvovaginitis, postpartum endometritis and adnexitis); infections of bones and joints, including osteomyelitis; infections of the skin and soft tissues (phlegmon, furunculosis, abscess, pyoderma, lymphadenitis, lymphangitis, infected trophic ulcers, infected wounds and burns); intra-abdominal infections (including in children over 2 years old); bacterial infection in patients with neutropenia (including children under 12 years of age); sepsis; meningitis; prevention of postoperative infection.

Dosage regimen

The method of administration and dosage regimen of a particular drug depend on its release form and other factors. The optimal dosage regimen is determined by the doctor. The compliance of the dosage form of a particular drug with the indications for use and dosage regimen should be strictly observed.

Intravenously.

Side effect

• Allergic reactions: urticaria, pruritus, rash, bullous dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylactic/anaphylactoid reactions (including anaphylactic shock).
• From the digestive system: diarrhea, nausea, vomiting, constipation, dyspepsia, jaundice, stomatitis, abdominal pain, pseudomembranous colitis, hepatitis.
• From the hematopoietic organs: leukopenia, neutropenia, thrombocytopenia, anemia, bleeding (including purpura, nosebleeds, increased time, bleeding), hemolytic anemia, agranulocytosis, false-positive direct Coombs test, pancytopenia, increased partial thromboplastin time, increased prothrombin time, thrombocytosis.
• From the urinary system: interstitial nephritis, renal failure.
• From the nervous system: headache, insomnia, convulsions.
• From the cardiovascular system: decreased blood pressure, “flushes” of blood to the facial skin.
• Laboratory indicators: hypoalbuminemia, hypoglycemia, hypoproteinemia, hypokalemia, eosinophilia, increased activity of “liver” transaminases (alanine aminotransferase, aspartate aminotransferase), hyperbilirubinemia, increased activity of alkaline phosphatase, gamma-glutamyltransferase, increased concentration of creatinine and urea in the blood serum.
• Local reactions: phlebitis, thrombophlebitis, hyperemia and compaction at the injection site.
• Other: fungal superinfections, fever, arthralgia.

Contraindications for use

Hypersensitivity (including to penicillins, cephalosporins, other beta-lactam antibiotic inhibitors); children's age (up to 2 years).

With caution

Severe bleeding (including history), cystic fibrosis (increased risk of developing hyperthermia and skin rash), pseudomembranous colitis, children over 2 years of age, chronic renal failure (creatinine clearance less than 20 ml/min), patients on hemodialysis , with the combined use of high doses of anticoagulants, with hypokalemia, pregnancy, lactation.

Use during pregnancy and breastfeeding

Use with caution during pregnancy and lactation (breastfeeding).

Use for renal impairment

With caution: chronic renal failure. For chronic renal failure, daily doses of piperacillin/tazobactam are adjusted depending on the CC.

Use in children

Contraindication: children under 2 years of age.

With caution: children over 2 years of age.

special instructions

During treatment, especially long-term treatment, leukopenia and neutropenia may develop, so it is necessary to periodically monitor peripheral blood levels.

In some cases (most often in patients with renal failure), increased bleeding and concomitant changes in laboratory parameters of the blood coagulation system (blood clotting time, platelet aggregation and prothrombin time) are likely to occur. If bleeding occurs, the drug should be discontinued and appropriate therapy should be prescribed.

Antibiotic-induced pseudomembranous colitis can present with severe, persistent diarrhea that is life-threatening. Pseudomembranous colitis can develop both during the period of antibacterial therapy and after its completion. In such cases, the drug should be stopped immediately and appropriate therapy should be prescribed (for example, oral metronidazole, vancomycin). Drugs that inhibit intestinal motility are contraindicated.

It is necessary to keep in mind the possibility of the emergence of resistant microorganisms that can cause superinfection, especially with a long course of treatment. This drug contains 2.79 mEq (64 mg) of sodium per gram of piperacillin, which may result in an overall increase in sodium intake. In patients with hypokalemia or taking drugs that promote potassium excretion, hypokalemia may develop during treatment (it is necessary to regularly check the content of electrolytes in the blood serum).

In patients with chronic renal failure on hemodialysis, the dose of the drug and frequency of administration must be adjusted depending on the CC.

During use, a false positive test result for glucose in urine is possible when using a method based on the reduction of copper ions. Therefore, it is recommended to carry out a test based on the enzymatic oxidation of glucose (glucose oxidase method).

Impact on the ability to drive vehicles and machinery

Considering the possibility of developing side effects from the nervous system during treatment with the drug, caution should be exercised when working with machinery and driving vehicles.

Drug interactions

Co-administration of the drug with probenecid increases the half-life and reduces the renal clearance of both piperacillin and tazobactam, however, Cmax in the plasma of both drugs remains unchanged.

The simultaneous use of the drug and vecuronium bromide can lead to a more prolonged neuromuscular blockade caused by the latter (a similar effect can be observed when piperacillin is combined with other non-depolarizing muscle relaxants).

With the simultaneous use of high doses of heparin, indirect anticoagulants or other drugs that affect the blood coagulation system, including platelet function, it is necessary to monitor the condition of the blood coagulation system more often.

Piperacillin may delay the elimination of methotrexate (to avoid toxic effects, it is necessary to monitor the concentration of methotrexate in the blood serum).

Pharmaceutical compatibility with other drugs

Do not mix in the same syringe or dropper with other medications, incl. with aminoglycosides. When used together with other antibiotics, the drugs should be administered separately; It is most preferable to separate the administration of piperacillin + tazobactam and aminoglycosides in time.

Should not be used in conjunction with solutions containing sodium bicarbonate or added to blood products or albumin hydrolysates.

Archives

Short Wiklad

Hauser AR, Sriram P. Postgrad Med 2005;117(1):41-8

The gram-negative bacterium P. aeruginosa can infect many organs and tissues (see Table 1). This is a problem that is most often seen in patients who have been hospitalized for more than 1 week. Fragments of the Pseudomonas aeruginosa suggest illness from overdose in patients with damage to the physical barrier against bacterial invasion (presence of tubes, intravenous, dissection or dialysis catheter, endotracheal tube) or immunodeficiency (neonatal period, evidence of cystic fibrosis, SNID, neutropenia, complement deficiency, hypogammaglobulinemia and iatrogenic immunosuppression), they are considered an opportunistic pathogen.

Table 1. Role of P. aeruginosa

as an alarmist of putrefactive processes (CDC, USA, 1990–1996)

In more than half of the cases, this bacterium synthesizes the blue-green pigment polycyanin. Often Pseudomonas produces a characteristic sweet smell. The blue stick is capable of metabolizing a large number of chemical compounds and therefore often infects internal diseases, medicinal properties and causes disinfection. This causes epidemics when many patients are infected with the same strain, which primarily comes from the same source.

Report on the presence of such an epidemic of P. aeruginosa

often causes nosocomial infection.
In hospitalized patients, there are numerous antimicrobial agents, but due to their initial resistance, this microbe has a selective advantage over others prior to colonization and subsequent development of infection. In addition, due to its polyresistance, Pseudomonas aeruginosa often poses a dilemma regarding therapeutic tactics. Infections caused by P. aeruginosa
are often accompanied by complications and can make life unsafe.

Bacteria, thought to be P. aeruginosa

, often stilet with evil shut -shaped, XIMIOTEPISIA, SNIDI, DeFICITI IMUNOGOBULINVAV, diffuse dermaty, Sepsisi at the Oppments, Tsugronaya Diabeti is the same Pislye Organizov. Risk factors for the development of cyst infections include injectable drug addiction, fibrotic diabetes, peripheral vascular disease, rheumatoid arthritis, advanced age or chronic decompensated illness, post-operation disease. this or penetrating trauma. The greatest risk for the development of SCC infection has been identified in young adults, sick children, especially those with neutropenia and hematological malignancies. The risk of contracting endocarditis among injectable drug addicts is much greater, lower among patients with rheumatism or abnormal heart valves.

Table 2. Typical localization of synoma infection in early illness and clinical situations (per S. Qarah, BA Cunha)

LIKUVALNA TACTICS

Against P. aeruginosa

active antibiotics, including β-lactams (Table 3).
To treat infections caused by this microbe, extended-spectrum penicillins such as sodium peperacillin and ticarcilin disodium are often used. In this infection, ticarcilin is less active and less active. It should be noted that the combination of these antibiotics with β-lactamase inhibitors—sodium tazobactam and potassium clavulanate—promotes their effectiveness. Therefore, for the successful treatment of serious infections caused by P. aeruginosa
, use the combination of piperacillin and tazobactam (Tazocin, Lederle Laboratories) in higher doses, lower than essential.
Although most cephalosporins are not active against P. aeruginosa
, ceftazidime (Fortum, GlaxoSmithKline) - a third-generation drug - and cefepime hydrochloride (Maxipim, BMS) - a fourth-generation drug - are characterized by high and even lower effectiveness Yu.
An antibiotic of the monobactam class, aztreons (Azactam, BMS), can be administered to patients with a non-inflammatory allergic reaction to penicillins. The carbapenem meropenem (Meronem, AstraZeneka) is very active against P. aeruginosa
, and the carbapenem meropenem (Tienam, MSD).

Table 3. Antibiotics that are especially useful for the treatment of Pseudomonas aeruginosa infection

The advantage of representatives of the class of fluoroquinolones ciprofloxacin, levofloxacin and gatifloxacin lies in the fact that they can be administered both internally and per os, therefore it is possible to administer them on an outpatient basis. These three antibiotics are most effective against P. aeruginosa

є ciprofloxacin.

Representatives of the aminoglycosides gentamycin, tobramycin and amikacin were the mainstay of treatment for Pseudomonas aeruginosa infection. Of these antibiotics, the most active in vitro is tobramycin. Prote aminoglycosides have a strong effect on the skin: the smell penetrates the legion and the secretion of the broncholegene tree and does not affect the acidic medium. It has become clear that these drugs in monotherapy may be insufficiently effective for the treatment of many important forms of Pseudomonas aeruginosa infection. In addition, stench often causes serious side effects, such as nephrotoxicity and ototoxicity.

THE PROBLEM OF RESISTANCE

P. aeruginosa

it is easy to develop resistance to almost any antibacterial drug (Table 4).
Resistance manifests itself on three levels: primary, nourished, and at the hour of celebration. When choosing an antibiotic for the treatment of patients infected with P. aeruginosa
, be sure to cover all types of resistance.
Table 4. Sensitivity of P. aeruginosa
to various antibiotics (%)

Primary resistance

Zagalom P. aeruginosa

naturally less sensitive, lower gram-negative bacilli, to a large number of antibiotics, such as ampicillin, more cephalosporins and macrolides, due to the apparently non-penetrating external cells This is the case before the active transport of certain antibiotics from the tissue, preventing their accumulation.
P. aeruginosa
also interferes with β-lactamase, which can destroy many β-lactam antibiotics.

Pseudomonas aeruginosa can grow in organized colonies on the surface of foreign bodies in the body (for example, catheters), soothing biofuels, as a result of which some bacteria become more resistant to antibiotics, at least when they grow in the form of plankton (suspension in the country).

Resistance is on the rise

Inheritance of mutations or removal of exogenous genetic material in P. aeruginosa

Resistance to any anti-pseudomonal antibiotic may develop. For example, β-lactamase type AmpC can interfere with β-lactam antibiotics such as piperacillin and ceftazidime. Before speaking, β-lactamase inhibitors - tazobactam, sodium sulbactam and clavulanate - do not act on β-lactamase type AmpC. The mechanisms of resistance to different members of the aminoglycoside class may vary, so resistance to gentamicin and tobramycin is often not accompanied by resistance to amikacin.

Based on recent research, two unsafe trends have been identified: over time, the sensitivity of Pseudomonas aeruginosa to antibiotics decreases, with particular resistance to piperacillin, ceftazidime, Used with ciprofloxacin; Alternatively, more than 10% of the observed bacteria do not respond adequately to most antibiotics, which is primarily indicated empirically in the form of monotherapy. Thus, the sensitivity of P. aeruginosa

, seen in patients treated in US intensive care units, to ciprofloxacin decreased from 89% in 1990–1993. up to 68% in 2000 births (Neuhauser MM et al., 2003).

Development of resistance under the hour of treatment

However, if antibiotics are used, the results of antibiotic therapy will not necessarily be successful. Sorry, P. aeruginosa

Resistance to antibiotics may develop during treatment and a mutation may appear that alters the penetration or activity of the antibiotic. With the influx of antibiotic activity in the infected tissue, a natural selection of bacteria with underlying mutations occurs, causing microorganisms to become larger in population.

Antibiotics, which require only one mutation to reduce their effectiveness, are the most susceptible to the emergence of resistance during treatment. Before them there should be imipine and fluoroquinolones. For example, resistance has developed in 25–50% of patients infected with P. aeruginosa

, who were treated with Thienam monotherapy, in 33–58% of patients who were treated with ciprofloxacin only.

ANTIBIOTIC THERAPY

Optimal treatment of important infections caused by P. aeruginosa

, is initiating empirical antibiotic therapy until culture results appear with further necessary adjustments.

Empirical antibiotic therapy

It is suspected or confirmed that an important infection is caused by P. aeruginosa

, and the results of the test for sensitivity to antibiotics have not yet been determined, it is necessary to empirically reverse the antibiotics that will ensure the maximum therapeutic effect. The consequences of delayed treatment for 2–3 days can be disastrous. In doctors, it is common to see the emergence of resistance, it is important to consider a combination of two antibiotics.

The choice of antibiotics depends on regional resistance and a history of contact with antibiotics. Frontal treatment with Thienam, ciprofloxacin, piperacillin or ceftazidime increases the likelihood that the patient’s strain of Pseudomonas aeruginosa is already resistant to these drugs. Regardless of which antibiotic is prescribed, the maximum dose must be determined to enhance its activity.

Changing the healing strategy

How to deal with the results of antibiotic therapy: combine treatment with two drugs or will monotherapy with one antibiotic be sufficient? This situation combines treatment with two advantages: synergistic interaction between drugs and prevention of developmental resistance.

In vitro studies indicate that single combinations of antibiotics can act synergistically against P. aeruginosa

. Synergistic antibiotics should be preceded by: (1) antipseudomonal β-lactams (for example, piperacillin, ceftazidime, cefepime, imipenem, meropenem or aztreone) with an aminoglycoside; (2) extended spectrum antipseudomonal penicillins with fluoroquinolone. Before speaking, these data point out that when stagnated for one hour, two β-lactams can act antagonistically, so that they are less effective, even if they are not used on the skin. As a rule, you can use a combination of it with piperacillin: it is a strong inducer of chromosomal β-lactamase of the AmpC type, which ensures that the antibiotic is resistant to inactivation by lactamase; On the other hand, piperacillin is not a β-lactamase inducer, but rather is strongly influenced by β-lactamase at high concentrations. When combining these two β-lactams, it induces the synthesis of AmpC type β-lactamase, which produces piperacillin.

The rationale for holding two antibiotics to prevent the emergence of resistance lies in the fact that bacteria that have developed mutations to develop resistance to one antibiotic will be greatly reduced by the others before they develop. All resistance and up to now. The effectiveness of combinations of antibiotics in preventing the development of resistance in humans is undermined. For example, under investigation by Carmeli Y. et al. (1999) 271 patients infected with P. aeruginosa

It was found that the combined treatment did not lead to a decrease in the incidence of resistance.

On the other hand, Jacobson KL et al. (1995) under a prospective controlled study of patients infected with P. aeruginosa

, Enterobacter, Citrobacter or Serratia marcescens, found that when combined with an extended-spectrum cephalosporin and an aminoglycoside, resistance developed earlier than with monotherapy with an extended-spectrum cephalosporin alone.

Efficiency of combined treatment

What are the clinical data to determine the best results of treatment with a combination of two antibiotics for important infections such as P. aeruginosa

?
In support of combined therapy, the most commonly cited prospective multicenter study is Hilf M. et al. (1989), who analyzed the results of a combined treatment of 200 patients with a clearly identified bacterium identified as P. aeruginosa
. The mortality rate with two antibiotics was 27%, compared with 47% with monotherapy (P = 0.023). The main limitations of this study: it was not randomized, and 37 (86%) of 43 patients in the monotherapy group were treated with only aminoglycosides—so treatment was not entirely optimal.

Chamot E. et al. (2003) reported a 4-fold reduction in mortality in patients with a bacterium called P. aeruginosa

, in which the combined bathing was carried out, combined with adequate monotherapy, for the washes, which the bathing began after blood sampling for culture for sterility.
Even though treatment began even after the results were reversed by antibiotics, no significant difference in mortality was detected. Based on these data and two other studies (Vidal F. et al., 1996 and Leibovici L. et al., 1997), no better results were achieved with the use of combined treatment. Thus, the current clinical data regarding the combined treatment of patients with serious infections called P. aeruginosa
are ambiguous.

Polyresistance

P. aeruginosa strains are multiresistant

, resistant to piperacillin, ceftazidime, imepenem, gentamicin and ciprofloxacin. In Europe and Latin America, the number of these strains is 3.6–7.7%.

Fatery fact that the herds of the new antipse herds, Likari will be at a beast of the old man, to the old man, such yak Kolstin1 (Kolstimetata of the NATO), and a new grocery antibiotics, Although colistimethate has significant side effects (mainly nephrotoxicity, neurotoxicity and neuromuscular blockade), it is active against most multi-resistant strains and has been successfully used to treat infections, tumors these microorganisms. The recommended dose for intravenous administration is 2.5–5.0 mg/kg/day, and the maximum is 300 mg.

1Polypeptide antibiotic of the polymyxin group. (Note switch)

It is also possible to use different methods of administering antibiotics that achieve a high concentration of the drug at the site of infection (for example, aerosols of aminoglycosides or colistimethate for the treatment of pneumonia). In severe cases, surgical intervention is necessary to drain the purulent cavity.

Forecast

The forecast depends on the localization of the infection. Bacteria, septicemia, meningitis, sepsis in ophthalmology and eye infections are associated with an unfavorable prognosis.

Table 5. Factors associated with an unfavorable prognosis in patients with septicemia or bacteria

Table 6. Factors associated with an unfavorable prognosis in patients with infection of the cardiovascular system

RECOMMENDATIONS

Looking for more aspects of the treatment of important infections caused by P. aeruginosa

, will be deprived of controversial ones, you can make a few recommendations:

1. It is known or suspected that a serious infection is caused by P. aeruginosa

, and the result of the test for sensitivity to antibiotics has not yet been cleared, there is evidence of empirical treatment for the use of two antibiotics with high activity against Pseudomonas aeruginosa.

2. In case of empirical treatment, the use of antibiotics is avoided if the disease has recently been resolved.

3. Once the results of antibiotic therapy have already been eliminated, antibiotic therapy can be carried out in combination or monotherapy mode. For serious infections, such as nosocomial pneumonia, septic endocarditis, bacteremia in patients with neutropenia, sepsis, we prefer the immediate use of two antibiotics. Although such an approach can overcome resistance or not help at times when treatment occurs, there is an imminent likelihood that patients will be treated with at least one drug, to which bacteria will be sensitive in the future when resistance develops.

4. In monotherapy, there is no indication of the use of aminoglycosides, fluoroquinolones and imepenem (Thienam).

5. In case of a combined treatment, the trace should be supplemented with antipseudomonal β-lactams (for example, extended-spectrum penicillins, cephalosporins, aztreones, carbapenems) with aminoglycosides or fluoroquinolones with extended-spectrum penicillins. of a wide spectrum. Zagalom requires a unique combination of two β-lactams.

6. In patients with multidrug-resistant strains of P. aeruginosa

You can also take colistimethate if this drug is toxic.

When preparing statistics, also note:

• 1. Selina Chen, Ralph Rudoy. Pseudomonas Infection. — https://www.emedicine.com/ped/topic2701.htm
• 2. Samer Qarah, Burke A. Cunha. Pseudomonas Aeruginosa Infections. — https://www.emedicine.com/med/topic1943.htm

Prepared by Bogdan Boris

• 1 Polypeptide antibiotic of the polymyxin group. (Note switch)