Carbapenem group. Cephalosporins and carbapenems. Prescription of universal antibiotics

Carbapenems (imipenem-cilastatpin, meropenem) are a relatively new class of antibiotics, structurally related to beta-lactam antibiotics, but having the widest spectrum of antimicrobial action, including many gram-positive and gram-negative aerobes and anaerobes.

The mechanism of action of carbapenems is based on their binding to specific beta-lactamotropic proteins of the cell wall and inhibition of peptidoglycan synthesis, leading to bacterial lysis. The first drug from this group was the semisynthetic antibiotic imipenem. It has a bactericidal effect against gram-negative, gram-positive microorganisms, anaerobes, enterobacter (enterobacteria), inhibiting the synthesis of bacterial cell walls by binding to PBP2 and PBP1, which leads to disruption of elongation processes. At the same time he us-

It is resistant to the action of beta-lactamases, but is destroyed by dehydropeptidases of the renal tubules, which leads to a decrease in its concentration in the urine, so it is usually administered with renal dehydropeptidase inhibitors - cilastatin in the form of the commercial drug "pritaxin".

Imipenem penetrates well into fluids and tissues, including cerebrospinal fluid. It is usually administered in a dose of 0.5-1.0 g intravenously every 6 hours. The half-life of the drug is 1 hour.

The role of imipenem in therapy has not been fully determined. The drug is successfully used for infections caused by sensitive microorganisms resistant to other drugs. It is especially effective for the treatment of mixed aerobic-anaerobic infections, but Pseudomonas aeruginosa can quickly become resistant to it.

In this case, an antibiotic from the aminoglycoside group and imipenem are administered simultaneously.

Side effects caused by imipenem include nausea, vomiting, skin reactions, and diarrhea. Patients with allergic reactions to penicillin may be allergic to imipenem.

This group includes the antibiotic meropenem, which is almost not destroyed by renal dehydropeptidases, and therefore is more effective against Pseudomonas aeruginosa and acts on strains resistant to imipenem.

The mechanism, nature and spectrum of antimicrobial action is similar to imipenem. Antimicrobial activity is manifested against gram-positive and gram-negative aerobes and anaerobes. In its antibacterial activity, meropenem is almost 5-10 times superior to imipenem, especially against gram-positive cocci and streptococci. In relation to staphylococci and enterococci, meropenem is significant

significantly more active than 3rd generation cephalosporins.

Meropenem has a bactericidal effect in concentrations close to bacteriostatic. It is stable to the action of bacterial beta-lactamases, and therefore is active against many microorganisms resistant to other drugs. Since it penetrates tissue barriers well, it is advisable to use it for severe infections such as pneumonia, peritonitis, meningitis, and sepsis.

Meropenem is the antibiotic of choice as monotherapy for nosocomial infections.

I think you all remember the arrival of this group of drugs into clinical practice. It was like the antibiotic era that had just begun again, when patients who seemed hopeless were able to get back on their feet... albeit at what seemed to us then to be colossal financial costs (how naive we were, now for a tetracycline drug we pay more than the cost of treating a patient with carbapenems per day).

Let's remember the place of each of the drugs in this group in our clinical practice.

Currently, four drugs of the carbapenem group are registered in Russia, which are divided into antipseudomonas(due to some activity against Pseudomonas aeruginosa):

· Imipenem

Meropenem

Doripenem

AND non-pseudomonas:

Ertapenem

On my own behalf, I would like to note that all this “pseudomonas aeruginosa” and its absence is nothing more than a marketing ploy, since we must always remember that on our own, without the support of antipseudomonal drugs, which we talked about earlier, not a single carbapenem with P.aeruginosa won't cope.

At this point in time, carbapenems remain drugs with the widest possible spectrum of activity, while maintaining maximum safety of use, like all beta-lactams, since they have a general class effect and act on the cell wall of microorganisms, disrupting its formation (and how you remember, we are not Pinocchio, so we have this very wall). In addition, not a single case of cross-allergic reactions with a group of penicillins or cephalosporins has been described. At the same time, carbapenems have maximum resistance to hydrolysis by extended spectrum beta-lactamases (ESBLs), although at the moment there is an increasing danger of the spread of carbapenemases in general and metal-beta-lactamases in particular, which destroy this group of drugs.

The basis of the spectrum of action of carbapenems is their pronounced gram-negative activity, since they are able to penetrate the wall of gram-negative bacteria faster than any beta-lactams. They are active against the family Enterobacteriaceae (Klebsiellaspp., Enterobacterspp., E.coli etc.), including strains producing ESBLs.

Carbapenems also show activity against gram-positive flora, namely pneumococci, gonococci, meningococci and staphylococci (excluding MRSA)

In addition, carbapenems are highly active against anaerobes, except C.difficile.

Considering the ultra-broad spectrum of action, a false illusion may be created that this group of drugs can be used as broad-spectrum drugs, that is, in any more or less complex situation, which, by the way, has happened and is happening in some hospitals to this day. This approach would be a huge mistake, since carbapenems can be viewed as a tornado that destroys everything in its path. They will knock out not only pathogenic, but also saprophytic flora, and according to the principle “a holy place is never empty”, after an effectively treated gram-negative infection, a gram-positive superinfection (most often caused by MRSA) will take its place, which the main thing is not to overlook, understand where it came from and start as much as possible rapid therapy with drugs with gram-positive activity.

I would also like to express my personal opinion regarding de-escalation therapy. I have nothing against initial therapy with carbapenems for a patient in serious condition for whom they are indicated, but I am against changing antibacterial therapy after receiving the results of a microbiological study if therapy with carbapenems has yielded results. Let's remember how many days later we receive microbiological research data - at the earliest in five, and in most cases in a week, if we do not have a laboratory equipped according to modern principles. When do we conduct clinical monitoring of the effectiveness of antibacterial therapy? In the case of carbapenems, after 48 hours. That is, within two days we must decide whether the therapy is effective or whether we missed something, or whether the patient’s condition has changed due to the course of the underlying disease or an exacerbation of a concomitant disease. In general, by the time data is received from the laboratory, one way or another, the pathogenic microbe will already be destroyed by the “carpet bombing” of carbapenem, or carbapenem in combination with an antistaphylococcal or antipseudomonas drug, and there is no talk of any effective transition to another, cheaper antibacterial drug it can not be. If we started treating with carbapenems and they showed their effectiveness, then we need to end the therapy with them too and not rush around with the choice.

A few words about each representative.

This drug is notable for the fact that it has a long half-life, which allows it to be administered once a day, which is very important. Since carbapenems, like all betalactam antibacterial drugs, are time-dependent drugs, which are extremely important to administer strictly on the clock, otherwise the bactericidal concentration drops below the minimum and the selection of resistant strains begins. In addition, it is simply convenient, unlike other carbapenems, which require 4-time, long-term intravenous administration. If the department is equipped with infusion pumps, the problem is not so acute, but when they are not there, even the four-time administration becomes a problem, and a person is designed to reduce problems in his life as much as possible (as well as costs) and thus situations are not uncommon when they try switch to 3 or even 2-time administration. In the case of a severe infectious process, such manipulations are not permissible. And this is where ertapenem comes in handy, administered 1 g per day at a time. You can object to me and point out that this drug does not have antipseudomonal activity. But colleagues, the antipseudomonal activity of meropenem, imipenem and doripenem is such that it can (and should) be neglected, and if you suspect the presence of P. aeruginosa, you simply must additionally use amikacin or ciprofloxacin, as powerful antipseudomonal drugs, the main thing is to choose the current dosage (we first We count per kilogram of body weight, the second - based on the MIC of the pathogen)

What readings exist for the use of ertapenem:

Severe intra-abdominal infections

· Severe community-acquired pneumonia

· Severe urinary tract infections

· Severe skin and soft tissue infections. Including diabetic foot without signs of osteomyelitis

Acute infections in the pelvic area

· Intra-abdominal infections of moderate severity (cholicestitis, cholangitis, diverticulitis, splenic abscess and liver abscess) that do not require drainage or surgical intervention.

2. Imipenem/cilastatin

It was with him that the solemn procession of carbapenems in Russia began. But how many marketing speculations surrounded it in the future, one of which was “the drug causes convulsions.” Imipenem increases seizure activity only in certain cases that must be taken into account:

Central nervous system infections

Doses more than 2 g per day

· Age over 60 - 65 years

History of seizures or central nervous system lesions - stroke, head injury, epilepsy

And when will we we use:

Bacterial endocarditis

· Septicemia

Cody and soft tissue infections (except MRSA)

Lower respiratory tract infections, including nosocomial pneumonia

· Gynecological infections

· Intra-abdominal infections

Infections caused by polymicrobial flora

· Complicated and uncomplicated urinary tract infections (pyelonephritis)

Can be used for:

§ Gas gangrene

§ Diabetic foot

§ Infections of bones and joints.

Dosage regimen:

· Imipenem is used in a regimen of 250 - 500 mg 4 times a day intravenously, preferably slowly, for urinary tract infections

Moderate infections - 500 mg intravenously slowly every 6 to 8 hours

· For severe infections caused by Pseudomonas aeruginosa: 1 g intravenously every 6 to 8 hours.

When dosing, the condition of the kidneys should be taken into account and the dose should be adjusted in case of renal failure.

3. Meropenem

Unlike imipenem, it can be used for CNS infections without restrictions.

Indications for use.

Preferanskaya Nina Germanovna
Associate Professor, Department of Pharmacology, Faculty of Pharmacy, First Moscow State Medical University named after. THEM. Sechenova, Ph.D.

The group of cephalosporins includes drugs based on 7-aminocephalosporanic acid. All cephalosporins, like othersβ-lactam antibiotics,characterized by a single mechanism of action. Individual representatives differ significantly in pharmacokinetics, severity of antimicrobial action and stability to beta-lactamases (Cefazolin, Cefotaxime, Ceftazidime, Cefepime, etc.). Cephalosporins have been used in clinical practice since the beginning of 1960; they are currently divided into four generations and, depending on their use, into drugs for parenteral and oral administration.

1st generation drugs most active against gram-positive bacteria, not resistant to beta-lactamases - Cephalexin ( Keflex), Cefazolin(Kefzol), Cefaclor, Cefadroxil(Biodroxil).

2nd generation drugs exhibit high activity against gram-negative pathogens, retain activity against gram-positive bacteria and increase resistance to betalactamases - Cefamandole, Cefaclor(Ceclor), Cefuroxime(Aksetin, Zinacef), Cefuroxime axetil (Zinnat).

3rd generation drugs highly active against a wide range of gram-negative microorganisms, not inactivated by many beta-lactamases (excluding extended spectrum and chromosomal) - Cefotaxime(Klaforan), Cefoperazone(Cephobid), Ceftriaxone(Azaran, Rocephin), Ceftazidime(Fortum), Ceftibuten(Tsedex), Cefixime(Suprax).

4th generation drugs have a high level of antimicrobial activity against gram-positive and gram-negative bacteria, resistant to hydrolysis by chromosomal beta-lactamases - Cefepime(Maxipim, Maxicef), Cefpir(Katen).

Combined cephalosporins help increase and maintain the effective concentration of the antibiotic and enhance the antimicrobial activity of the drug: Cefoperazone + Sulbactam(Sulperazon, Sulperacef).

Cephalosporins with more pronounced resistance to beta-lactamases (cefazolin, cefotaxime, ceftriaxone, ceftazidime, cefepime, etc.). Oral cephalosporins (cefuroxime axetil, cefaclor, cefixime, ceftibuten) are active against microorganisms that produce beta-lactamases.

General approaches to the use of cephalosporins:

• infections caused by pathogens that are not sensitive to penicillins, for example, Klebsiella and Enterobacteriaceae;
• in case of allergic reactions to penicillin, cephalosporins are the first-line reserve antibiotics, but 5-10% of patients experience cross-allergic sensitivity;
• for severe infections, use in combination with semisynthetic penicillins, especially acylureidopenicillins (azlocillin, mezlocillin, piperacillin);
• can be used during pregnancy and do not have teratogenic or embryotoxic properties.

Indications for use include community-acquired infections of the skin and soft tissues, urinary tract infections, infections of the lower and upper respiratory tract and pelvic organs. Cephalosporins are used for infections caused by gonococci; ceftriaxone, cefotaxime, and cefixime are used to treat gonorrhea. In the treatment of meningitis, drugs that penetrate the blood-brain barrier (cefuroxime, ceftriaxone, cefotaxime) are used. 4th generation cephalosporins are used to treat infections associated with immunodeficiency conditions. During the use of cefoperazone and for two days after treatment with this antibiotic, you should avoid drinking alcoholic beverages to avoiddevelopment of a disulfiram-like reaction. Alcohol intolerance occurs due to blockade of the enzyme aldehyde dehydrogenase, toxic acetaldehyde accumulates and a feeling of fear, chills or fever occurs, breathing becomes difficult, and the heartbeat increases. There is a feeling of lack of air, a drop in blood pressure, and the patient suffers from uncontrollable vomiting.

Carbapenems

Carbapenems have been used in clinical practice since 1985; drugs in this group have a wide spectrum of antimicrobial activity; “gr+” and “gr-” bacteria are sensitive to them, including Pseudomonas aeruginosa. The main representatives are Imipenem, Meropenem and combination drug Tienam(Imipenem + Cilastatin). Imepenem is destroyed in the renal tubules by the enzyme dehydropeptidase. I , therefore it is combined with cilastatin, which inhibits the activity of this enzyme. The drugs are resistant to beta-lactamases and penetrate well into body tissues and fluids. They are used for severe infections caused by polyresistent and mixed microflora, complicated infections of the urinary system and pelvic organs, skin and soft tissues, bones and joints. Meropenem used to treat meningitis. Carbapenems cannot be combined with other β-lactam antibiotics due to their antagonism, and also mixed in the same syringe or infusion system with other drugs!

Interaction of β-lactam antibiotics with other drugs

group carbapenems are beta-lactam antibiotics with a very broad spectrum of action. These drugs are more resistant than penicillins and cephalosporins to the action of beta-lactamases of bacterial cells and have a bactericidal effect by blocking cell wall synthesis.

Carbapenems are active against many Gr(+)- and Gr(-) microorganisms. This applies, first of all, to enterobacteria, staphylococci (except for methicillin-resistant strains), streptococci, gonococci, meningococci, as well as Gr(-) strains resistant to the last two generations of cephalosporins and protected penicillins. In addition, carbapenems are highly effective against spore-forming anaerobes.

All drugs in this group are used parenterally. Quickly and for a long time they create therapeutic concentrations in almost all tissues. In meningitis, they are able to penetrate the blood-brain barrier. The advantage of all carbapenems is that they are not metabolized and are excreted by the kidneys in their original form. The latter must be taken into account when treating patients with renal failure with carbapenems. In this case, the elimination of carbapenems will be significantly slowed down.

Carbapenems are reserve antibiotics, used in case of ineffectiveness of treatment, for example, younger generation cephalosporins. Indications: severe infectious processes of the respiratory, urinary systems, pelvic organs, generalized septic processes, and so on. Use with caution in case of renal failure (individual dose adjustment), liver pathology, neurogenic disorders. The use of carbapenems during pregnancy is not recommended. Contraindicated in case of individual intolerance to carbapenems, as well as in parallel use of beta-lactams of other groups. Cross-allergic reactions with penicillin and cephalosporin drugs are possible.

Imipenem- has high activity against Gr(+) and Gr(-) flora. However, for the treatment of severe infections caused by gram-negative microorganisms, it is better to use meropenem. It is not used to treat meningitis, but is used in the treatment of joint and bone infectious pathologies, as well as for the treatment of bacterial endocarditis. Dosage: adults - intravenously 0.5-1.0 g every 6-8 hours (but not more than 4.0 g/day); children over 3 months with a body weight less than 40 kg - intravenously 15-25 mg/kg every 6 hours. Release form: powder for the preparation of intravenous injections in 0.5 g bottles.

Meropenem- more active than imipenem against gram-negative flora, while meropenem has weaker activity against gram-positive flora. It is used to treat meningitis, but is not used in the treatment of joint and bone infectious pathologies, as well as for the treatment of bacterial endocarditis. It is not inactivated in the kidneys, which makes it possible to treat severe infectious processes developing there. Contraindicated in children under three months of age. Release form: powder for infusion of 0.5 or 1.0 g in bottles.

Antibiotic tablets are substances that inhibit the growth of microorganisms and, as a result, kill them. Used to treat infectious pathologies. Can be 100% natural or semi-synthetic. So, what drugs are antibiotics?

Prescription of universal antibiotics

Prescribing the described medications is justified in the following cases:

1. Therapy is selected based on clinical symptoms, i.e. without identifying the pathogen. This is relevant for active illnesses, for example, meningitis - a person can die in just a couple of hours, so there is no time for complex measures.
2. The infection has not one, but several sources.
3. The microorganism that causes the disease is resistant to narrow-spectrum antibiotics.
4. A set of preventive measures is carried out after the operation.

Classification of universal antibiotics

The medicines we are considering can be divided into several groups (with names):

• penicillins – Ampicillin, Amoxicillin, Ticarcillin;
• tetracyclines - these include the drug of the same name;
• fluoroquinolones – Ciprofloxacin, Levofloxatin, Moxifloxacin; Gatifloxacin;
• aminoglycosides – Streptomycin;
• amphenicols – Levomycetin;
• carbapenems - Imipenem, Meropenem, Ertapenem.

This is the main list.

Penicillins

With the discovery of benzylpenicillin, scientists came to the conclusion that microorganisms could be killed. Despite the fact that, as they say, “a lot of water has already flown under the bridge,” this Soviet antibiotic has not been discounted. However, other penicillins were created:

• those that lose their qualities when passing through the acid-base environment of the gastrointestinal tract;
• those that do not lose their qualities when passing through the acid-base environment of the gastrointestinal tract.

Ampicillin and Amoxicillin

Special attention should be paid to antibiotics such as Ampicillin and Amoxicillin. In terms of action they are practically no different from each other. Able to cope with:

• gram-positive infections, in particular staphylococci, streptococci, enterococci, listeria;
• gram-negative infections, in particular, Escherichia coli and Haemophilus influenzae, salmonella, shigella, pathogens of whooping cough and gonorrhea.

But their pharmacological properties are different.

Ampicillin is characterized by:

• bioavailability – no more than half;
• the period of elimination from the body is several hours.

The daily dose varies from 1000 to 2000 mg. Ampicillin, unlike Amoxicillin, can be administered parenterally. In this case, injections can be done both intramuscularly and intravenously.

In turn, Amoxicillin is characterized by:

• bioavailability – from 75 to 90%; does not depend on food intake;
• The half-life is several days.

The daily dose varies from 500 to 1000 mg. The duration of treatment is five to ten days.

Parenteral penicillins

Parenteral penicillins have one important advantage over Ampicillin and Amoxicillin - the ability to cope with Pseudomonas aeruginosa. It leads to the formation of purulent wounds and abscesses, and is also the cause of cystitis and enteritis - infections of the bladder and intestines, respectively.

The list of the most common parenteral penicillins includes Ticarcillin, Carbenicillin, Piperacillin.

The first is prescribed for peritonitis, sepsis, septicemia. Effective in the treatment of gynecological, respiratory and skin infections. Prescribed to patients whose immune system is in an unsatisfactory state.

The second is prescribed in the presence of microorganisms in the abdominal cavity of the genitourinary system and bone tissue. Administered intramuscularly and, in difficult cases, intravenously through a dropper

The third is prescribed for pus in the abdominal cavity, genitourinary system, bone tissue, joints and skin.

Improved penicillins

Ampicillin and Amoxicillin become useless in the presence of beta-lactamases. But the great minds of mankind found a way out of this situation - they synthesized improved penicillins. In addition to the main active substance, they contain beta-lactamase inhibitors, these are:

1. Amoxicillin with added clavulanic acid. Generics – Amoxiclav, Flemoclav, Augmentin. Sold in injections and in oral form.
2. Amoxicillin with the addition of sulbactam. In pharmacies it is called Trifamox. Sold in tablets and in oral form.
3. Ampicillin with the addition of sulbactam. In pharmacies it is called Ampisid. Sold by injection. It is used in hospitals for diseases that are difficult for an ordinary person to recognize.
4. Ticarcillin with added clavulanic acid. In pharmacies it is called Timentin. Sold in a form for oral administration.
5. Piperacillin with tazobactam added. In pharmacies it is called Tacillin. Delivered by infusion drip.

Tetracyclines

Tetracyclines are not susceptible to beta-lactamases. And in this they are one step higher than penicillins. Tetracyclines destroy:

• gram-positive microorganisms, in particular staphylococci, streptococci, listeria, clostridia, actinomycetes;
• gram-negative microorganisms, in particular Escherichia coli and Hemophilus influenzae, salmonella, shigella, pathogens of whooping cough, gonorrhea and syphilis.

Their peculiarity is that they pass through the cell membrane, which allows them to kill chlamydia, mycoplasma and ureaplasma. However, they do not have access to Pseudomonas aeruginosa and Proteus.

Tetracycline is commonly found. Also on the list is Doxycycline.

Tetracycline

Undoubtedly, tetracycline is one of the most effective antibiotics. But he has weaknesses. First of all, insufficient activity with a high probability of changes in the intestinal microflora. For this reason, you should choose tetracycline not in tablet form, but in ointment form.

Doxycycline

Doxycycline, compared to tetracycline, is quite active with a low probability of changes in intestinal microflora.

Fluoroquinolones

The first fluoroquinolones, such as Ciprofloxacin, Ofloxacin, Norfloxacin, could not be called universal antibiotics. They were only able to cope with gram-negative bacteria.

Modern fluoroquinolones, Levofloxacin, Moxifloxacin, Gatifloxacin, are universal antibiotics.

The disadvantage of fluoroquinolones is that they interfere with the synthesis of peptidoglycan, a kind of building material of tendons. As a result, they are not permitted to persons under 18 years of age.

Levofloxacin

Levofloxacin is prescribed for the presence of microorganisms in the respiratory tract, bronchitis and pneumonia, infections in the ENT organs, otitis and sinusitis, infections in the skin, as well as for diseases of the gastrointestinal tract and urinary tract.

The duration of treatment is seven, sometimes ten, days. Dose – 500 mg at a time.

In pharmacies it is sold as Tavanik. Generics are Levolet, Glevo, Flexil.

Moxifloxacin

Moxifloxacin is prescribed for the presence of microorganisms in the respiratory tract, ENT organs, skin, and also as a prophylaxis after surgery.

Duration of treatment is from seven to ten days. Dose – 400 mg at a time.

It is sold in pharmacies as Avelox. There are few generics. The main active ingredient is included in Vigamox - eye drops.

Gatifloxacin

Gatifloxacin is prescribed for the presence of microorganisms in the respiratory tract, ENT organs, urogenital tract, as well as serious eye diseases.

Dose – 200 or 400 mg once.

In pharmacies it is sold as Tabris, Gaflox, Gatispan.

Aminoglycosides

A prominent representative of Aminoglycosides is Streptomycin, a drug that every person has heard of at least once in their life. It is indispensable in the treatment of tuberculosis.

Aminoglycosides are able to cope with most gram-positive and gram-negative bacteria.

Streptomycin

It is efficient. With its help, you can cure not only tuberculosis, but also diseases such as plague, brucellosis and tularemia. As for tuberculosis, localization is not important when using streptomycin. Sold in injections.

Gentamicin

It is gradually becoming a thing of the past, as it is very, very controversial. The fact is that there was hearing damage, up to complete deafness, which the doctors did not expect at all. In this case, the toxic effect is irreversible, i.e. Once you stop taking it, nothing is returned.

Amikacin

Amikacin is prescribed for peritonitis, meningitis, endocarditis, and pneumonia. Sold in ampoules.

Amphenicols

This group includes Levomycetin. It is prescribed for typhoid and paratyphoid fever, typhus, dysentery, brucellosis, whooping cough, and intestinal infections. Sold in the form of injections and ointments.

Carbapenems

Carbapenems are intended to treat severe infections. They are able to cope with many bacteria, including those resistant to all the antibiotics listed above.

Carbapenem is:

• Meropenem;
• Ertapenem;
• Imipenem.

Carbapenems are administered using a special dispenser.

Now you know the names of antibiotics, which medications are classified as antibiotic tablets, and which are not. Despite this, under no circumstances should you self-medicate, but seek help from a specialist. Remember that taking these medications incorrectly can seriously harm your health. Be healthy!