Antibiotics for pyelonephritis

Antibiotics for pyelonephritis should have high bactericidal properties, a broad spectrum of action, minimal nephrotoxicity and be excreted in urine in high concentrations.

The following medications are used:

• antibiotics;
• nitrofurans;
• non-fluorinated quinolones (derivatives of nalidixic and pipemidic acid);
• 8-hydroxyquinoline derivatives;
• sulfonamides;
• herbal uroantiseptics.

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Antibiotics used in the treatment of pyelonephritis

The basis of antibacterial treatment are antibiotics, and among them the beta-lactam group: aminopenicillins (ampicillin, amoxicillin) are characterized by very high natural activity against E. coli, Proteus, enterococci. Their main disadvantage is susceptibility to the action of enzymes - beta-lactamases, produced by many clinically significant pathogens. Currently, aminopenicillins are not recommended for the treatment of pyelonephritis (except for pyelonephritis in pregnant women) due to the high level of resistant E. coli strains (over 30%) to these antibiotics. Therefore, the drugs of choice for empirical therapy are protected penicillins (amoxicillin + clavulanate, ampicillin + sulbactam), which are highly active against both gram-negative bacteria producing beta-lactamases and gram-positive microorganisms, including penicillin-resistant aureus and coagulase-negative staphylococci. The level of resistance of E. coli strains to protected penicillins is not high. Amoxicillin + clavulanate is prescribed orally at 625 mg 3 times a day or parenterally at 1.2 g 3 times a day for 7-10 days.

"Flemoklav Solutab" is an innovative dosage form of amoxicillin with clavulanic acid. The drug belongs to the group of inhibitor-protected aminopsninillinone and has proven effectiveness in kidney and lower genitourinary tract infections. It is approved for use in children from 3 months and pregnant women.

The Solutab tablet is formed from microspheres, the protective shell of which protects the contents from the action of gastric juice and dissolves only at an alkaline pH value. i.e. in the upper sections of the small intestine. This provides the drug Flemoklav Solutab with the most complete absorption of active components compared to analogues. At the same time, the effect of clavulanic acid on the intestinal microflora remains minimal. A reliable decrease in the frequency of adverse drug reactions (especially diarrhea) when using Flemoklav Solutab in children and adults has been confirmed by clinical studies.

The form of the drug "Flemoklav Solutab" (dispersible tablets) ensures ease of use: the tablet can be taken whole or dissolved in water, or prepared as a syrup or suspension with a pleasant fruity taste.

In complicated forms of pyelonephritis and suspected infection caused by Pseudomonas aeruginosa, carboxypenicillins (carbenicillin, ticarcillin) and ureidopenicillins (piperacillin, azlocillin) can be used. However, the high level of secondary resistance of this pathogen to these drugs should be taken into account. Antipseudomonal penicillins are not recommended for use as monotherapy, since rapid development of resistance of microorganisms is possible during treatment, therefore, combinations of these drugs with beta-lactamase inhibitors (ticarcillin + clavulanic acid, piperacillin + tazobactam) or in combination with aminoglycosides or fluoroquinolones are used. The drugs are prescribed for complicated forms of pyelonephritis, severe hospital infections of the urinary tract.

Along with penicillins, other beta-lactams are also widely used, primarily cephalosporins, which accumulate in the renal parenchyma and urine in high concentrations and have moderate nephrotoxicity. Cephalosporins currently occupy first place among all antimicrobial agents in terms of frequency of use in hospital patients.

Depending on the spectrum of antimicrobial action and the degree of resistance to beta-lactamases, cephalosporins are divided into four generations. First-generation cephalosporins (cefazolin, etc.) are not used in acute pyelonephritis due to their limited spectrum of activity (mainly gram-positive cocci, including penicillin-resistant Staphylococcus aureus). Second-generation cephalosporins (cefuroxime, etc.) are characterized by a broader spectrum of activity, including E. coli and a number of other enterobacteria. They are used in outpatient practice to treat uncomplicated forms of pyelonephritis. Often, the effect of these drugs is broader than that of first-generation drugs (cefazolin, cephalexin, cephradine, etc.). In complicated infections, 3rd generation cephalosporins are used both for oral administration (cefixime, ceftibuten, etc.) and for parenteral administration (cefotaxime, ceftriaxone, etc.). The latter is characterized by a longer half-life and the presence of two excretion routes - with urine and bile. Among the 3rd generation cephalosporins, some drugs (ceftazidime, cefoperazone and the inhibitor-protected cephalosporin cefoperazone + sulbactam) are active against Pseudomonas aeruginosa. The 4th generation cephalosporins (cefepime), while retaining the properties of 3rd generation drugs against gram-negative enterobacteria and Pseudomonas aeruginosa, are more active against gram-positive cocci.

In the treatment of complicated forms of pyelonephritis, serious hospital-acquired infections, aminoglycosides (gentamicin, netilmicin, tobramycin, amikacin) are used, which have a powerful bactericidal effect on feminogen-negative bacteria, including Pseudomonas aeruginosa, being the drugs of choice. In severe cases, they are combined with penicillins, cephalosporins. The peculiarity of the pharmacokinetics of aminoglycosides is their poor absorption in the gastrointestinal tract, so they are administered parenterally. The drugs are excreted unchanged by the kidneys; in case of renal failure, dose adjustment is necessary. The main disadvantages of all aminoglycosides are pronounced ototoxicity and nephrotoxicity. The incidence of hearing loss reaches 8%, kidney damage (non-oliguric renal failure; usually reversible) - 17%, which dictates the need to monitor the level of potassium, urea, and serum creatinine during treatment. Due to the proven dependence of the severity of adverse reactions on the level of drug concentration in the blood, it is proposed to administer the full daily dose of drugs once; with the same dosing regimen, the risk of nephrotoxic action decreases.

Risk factors for the development of nephrotoxicity when using aminoglycosides are:

• old age;
• repeated use of the drug at intervals of less than a year;
• chronic diuretic therapy;
• combined use with cephalosporins in high doses.

In recent years, the drugs of choice in the treatment of pyelonephritis, both in outpatient and inpatient settings, are considered to be first-generation fluoroquinolones (ofloxacin, pefloxacin, ciprofloxacin), which are active against most pathogens of the genitourinary system and have low toxicity, a long half-life, which makes it possible to take 1-2 times a day; they are well tolerated by patients, create high concentrations in urine, blood and kidney tissue, and can be used orally and parenterally (except for norfloxacin: it is used only orally).

The new (2nd) generation of fluoroquinolones (proposed for use after 1990): levofloxacin, lomefloxacin, sparfloxacin, moxifloxacin - exhibit significantly higher activity against gram-positive bacteria (primarily pneumococci), while their activity against gram-negative bacteria is not inferior to the early ones (with the exception of Pseudomonas aeruginosa).

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Ciprofloxacin for pyelonephritis

Ciprofloxacin has the highest activity against P. aeruginosa.

Ciprofloxacin (Ciprinol) is a systemic fluoroquinolone with a broad spectrum of antimicrobial action. It has a bactericidal effect on most gram-negative and some fampopositive microorganisms. Some intracellular pathogens are moderately sensitive to ciprofloxacin in vitro.

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Dosage

The tablets are taken whole with a small amount of liquid. For intravenous administration, it is best to use a short infusion (60 min).

In severe complicated infections and depending on the pathogen (e.g. P. aeruginosa infection), the daily dose can be increased to 750 mg 3 times orally or up to 400 mg 3 times intravenously.

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Indications

• Bacterial infections of the urinary and lower respiratory tract, ear, throat and nose, bones and joints, skin, soft tissue, genitals.
• Prevention of infections during surgical interventions, particularly in urology, gastroenterology (in combination with metronidazole) and orthopedic surgery.
• Bacterial diarrhea.
• Abdominal and hepatobiliary infections.
• Severe systemic infections.

Contraindications

• Hypersensitivity to the drug or other quinolones.
• Pregnancy and breastfeeding.
• The use of ciprofloxacin in children and adolescents during growth is not recommended.

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Package

10 tablets of 250 mg, 500 mg or 750 mg; infusion solution (conc.) 100 mg in 10 ml No. 5 (amp.); infusion solution 200 mg in 100 ml No. 1 (vial).

In most cases of pyelonephritis, fluoroquinolones are used orally; in severe forms and generalized infections, they are used parenterally (step therapy is possible).

Empirical antibacterial therapy for pyelonephritis

Acute pyelonephritis or exacerbation of chronic (mild and moderate severity) - outside the hospital (outpatients)

Drugs of choice	Alternative drugs
Amoxicillin + clavulanic acid orally 375-625 mg 3 times a day Levofloxacin orally 250 mg once a day Lomefloxacin orally 400 mg once a day Norfloxacin orally 400 mg 2 times a day Ofloxacin orally 200 mg 2 times a day Pefloxacin orally 400 mg 2 times a day Ciprofloxacin orally 250 mg 2 times a day	Co-trimoxazole orally 480 mg 2 times a day after meals Cefixime orally 400 mg once a day Ceftibuten orally 400 mg once a day Cefuroxime orally 250 mg 2 times a day

Pyelonephritis (severe and complicated forms) - hospital

Amoxicillin + clavulanic acid intravenously 1.2 g 3 times a day, orally 625 mg 3 times a day Levofloxacin intravenously 500 mg once a day, orally 500 mg once a day Ofloxacin intravenously 200 mg 2 times a day, orally 200 mg 2 times a day or Pefloxacin intravenously 400 mg 2 times a day, orally 400 mg 2 times a day or Ciprofloxacin intravenously 200 mg 2 times a day, orally 250 mg 2 times a day

Gentamicin intravenously or intramuscularly 80 mg 3 times a day [3-4 mg/(kg x day)], or Ticarcillin + clavulanic acid intravenously 3.2 g 3-4 times a day or Imipenem + cilastine intramuscularly 500 mg 2 times a day or Cefotaxime intravenously or intramuscularly 1-2 g 2-3 times a day or Ceftazidime intravenously or intramuscularly 1-2 g 2-3 times a day or Ceftriaxone intravenously or intramuscularly 1-2 g once a day Cefoperazone intravenously 2 g 2-3 times a day

The half-life of various fluoroquinolones ranges from 3-4 hours (norfloxacin) to 18 hours (pefloxacin).

In case of renal dysfunction, the half-life of ofloxacin and lomefloxacin is most significantly prolonged. In case of severe renal insufficiency, dose adjustment of all fluoroquinolones is necessary, and in case of liver dysfunction, pefloxacin.

During hemodialysis, fluoroquinolones are removed in small quantities (ofloxacin - 10-30%, the rest - less than 10%).

When ciprofloxacin, norfloxacin and pefloxacin are prescribed together with drugs that alkalize urine (carbonic anhydrase inhibitors, citrates, sodium bicarbonate), the risk of crystalluria and nephrotoxic effects increases.

Possible but very rare (0.01-0.001%) adverse reactions include inflammatory reactions of the tendons (associated with impaired peptide glycan synthesis in the tendon structure), tendinitis and tendovaginitis (more often of the Achilles tendon, less often of the shoulder joint), in connection with which it is recommended to use with caution in elderly patients undergoing hormonal therapy. In patients with diabetes mellitus, hypo- or hyperglycemia may develop.

Fluoroquinolones are not permitted in pregnant women and children under 16 years of age due to the risk of chondrotoxicity. Fluoroquinolones may be prescribed to children for vital indications (severe infections caused by multidrug-resistant bacterial strains).

In the treatment of particularly severe complicated forms of pyelonephritis, the reserve drugs with an ultra-broad spectrum of action and resistance to the action of most beta-lactamases are carbapenems (imipenem + cilastatin, meropenem). Indications for the use of carbapenems are:

• generalization of infection;
• bacteremia;
• sepsis;
• polymicrobial infection (a combination of gram-negative aerobic and anaerobic microorganisms);
• presence of atypical flora;
• ineffectiveness of previously used antibiotics, including beta-lactams.

The clinical efficacy of carbapenems is 98-100%. Carbapenems are the drug of choice for the treatment of infections caused by resistant strains of microorganisms, primarily Klebsiella spp. or E. coli producing extended-spectrum beta-lactamases, as well as chromosomal class C beta-lactamases (Enterobacter spp., etc.), which are most common in intensive care units and organ transplant units. As an alternative to eradication of enterobacteria producing extended-spectrum beta-lactamases, it is possible to use protected beta-lactams (ticarcillin + clavulanic acid, piperacillin + tazobactam) or cefepime (optimally when sensitivity to them is established). It should be remembered that carbapenems are not active against methicillin-resistant staphylococci, as well as atypical pathogens - chlamydia and mycoplasma.

Along with antibiotics, other antimicrobial agents are also used in the treatment of pyelonephritis, which are introduced into long-term therapy regimens after discontinuing antibiotics, sometimes prescribed in combination with them, more often to prevent exacerbations of chronic pyelonephritis. These include:

• nitrofurans (nitrofurantoin, furazidin);
• 8-oxyquinolines (nitroxoline);
• nalidixic and pipemidic acid;
• combination antimicrobial drugs (co-trimoxazole).

The pH of urine may have a significant effect on the antimicrobial activity of some drugs. Increased activity in an acidic environment (pH < 5.5) was noted for aminopenicillins, nitrofurans, oxyquinolines, nalidixic acid, and in an alkaline environment - for aminoglycosides, cephalosporins, semisynthetic penicillins (carbenicillin), sulfonamides, macrolides (erythromycin, clindamycin).

In the presence of chronic renal failure, antibiotics that undergo metabolism in the liver can be prescribed in the usual dose: azithromycin, doxycycline, pefloxacin, chloramphenicol, cefaclor, cefoperazone, erythromycin. It is not recommended to prescribe aminoglycosides, tetracyclines, nitrofurans, co-trimoxazole. It should be borne in mind that the nephrotoxicity of various drugs increases under conditions of using diuretics and in renal failure.

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Criteria for the effectiveness of antibiotics in pyelonephritis

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Early criteria (48-72 hours)

Positive clinical dynamics:

• reduction of fever;
• reduction of manifestations of intoxication;
• improving overall well-being;
• normalization of the functional state of the kidneys;
• urine sterility after 3-4 days of treatment.

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Late criteria (14-30 days)

Persistent positive clinical dynamics:

• absence of relapses of fever;
• absence of chills for 2 weeks after completion of antibacterial therapy;
• negative results of bacteriological examination of urine on the 3rd-7th day after the end of antibacterial therapy.

Final criteria (1-3 months)

Absence of recurrent urinary tract infections within 12 weeks after completion of antibacterial treatment for pyelonephritis.

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