Imipenem and Cilastatin Jodas 500 mg + 500 mg 20 ml No. 10 bottle

The place of carbapenems in the treatment of NP

Taking into account the timing of the development of NP, early NP is distinguished, occurring within the first five days from the moment of hospitalization, which is characterized by pathogens that are sensitive to traditionally used antibacterial drugs; late NP, developing no earlier than the fifth day of hospitalization, which is characterized by a high risk of the presence of multidrug-resistant bacteria and a less favorable prognosis [1]. To select initial antibiotic therapy, the presence of risk factors for multidrug-resistant pathogens is important: high levels of local resistance of pathogens (in a given health care facility or department), the development of NP after 5 days or more from the start of hospitalization, taking immunosuppressants and/or the presence of an immunosuppressive state in the patient, taking antibiotics for the last 90 days, inpatient treatment for more than 2 days in the last 90 days, being in a nursing home, infusion therapy at home, chronic dialysis in the last 30 days, having a family member with diseases caused by multidrug-resistant pathogens [2, 12]. ABT NP includes early and adequate empirical therapy in adequate doses of optimal duration and de-escalation based on culture results and response to therapy (4D rule: drug, dose, duration, de-escalation) [1, 2, 7, 10]. When choosing empirical broad-spectrum antibiotic therapy, it is necessary to take into account the patient’s risk factors for the presence of multidrug-resistant microflora and local data on resistance [8].

The etiological structure of early NP with or without risk factors for multidrug-resistant microflora is close to that in community-acquired pneumonia, therefore it is recommended to prescribe antipseudomonas without antipseudomonas and anti-MRSA activity: third generation antistreptococcal cephalosporins (cefotaxime, ceftriaxone), or fluoroquinolones (ofloxacin, moxifloxacin, levofloxacin ), or piperacillin/tazobactam, or a carbapenem without antipseudomonal activity - ertapenem.

The most common pathogens of late NP are Pseudomonas aeruginosa, Enterobacteriaceae (producing extended spectrum β-lactamases - ESBL+), Acinetobacter spp., mecitillin-resistant Staphylococcus aureus (MRSA). Proposed ABT regimens should have antipseudomonas and antistaphylococcal activity, and also act on strains of enterobacteria that produce ESBL+: cephalosporins with antipseudomonas activity (ceftazidime or cefepime), antipseudomonas carbapenems (meropenem, imipenem, doripenem) or antipseudomonal β-lactam + β-lactamase inhibitor (piperacillin/tazobactam). Pending culture results, a fluoroquinolone (ciprofloxacin or levofloxacin) or aminoglycoside may be added to therapy for additional activity against resistant gram-negative bacteria. If the presence of ESBL+ or AmpC-β-lactamase-producing drugs (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter spp. or Enterobacter spp.) is suspected, carbapenems should be the drugs of choice. If there is a risk of MRSA, vancomycin or linezolid should be added [1, 2, 5, 6, 7, 12]. The use of antipseudomonas carbapenems (meropenem, doripenem or imipenem) as initial therapy in combination with drugs active against MRSA (linezolid, vancomycin) is justified in severe cases of NP-IVL, in patients who are critically ill as a result of the development of multiple organ failure or septic shock.

Enter

Carbapenems are beta-lactam antibiotics with an ultra-broad spectrum of antibacterial activity, which includes most clinically important aerobic and anaerobic bacteria. This power stinks especially strongly as the first choice drugs for the empirical treatment of serious infections in hospitalized patients, in which microorganisms that cause infection are unknown or its resistance is suspected.

Nina has two carbapenems. Imipenem/cilastatin has been in clinical practice for more than 10 years. Meropenem is becoming available in a growing number of countries. These antibiotics retain their activity against an increasing number of bacterial strains, such as beta-lactamases. Both drugs are similar in effectiveness, but have different structural, physicochemical, pharmacodynamic and pharmacokinetic influences, which may be more important for their clinical stability. This article is devoted to a review of the significant functions and follows the clinical evidence of the stagnation of both drugs, with particular attention paid to dosage and nutritional safety.

Pharmacoeconomic assessment

Studies evaluating the pharmacoeconomic efficacy of various carbapenems were based on the results of the randomized clinical trials described above [45, 46].

In a study by S. Merchant et al., 2008 [50], the costs of treatment of NP-IVL (from a hospital point of view) were studied when using doripenem and imipenem. The duration of hospital treatment, stay in the ICU and mechanical ventilation were compared. The median length of hospital stay was shorter in the doripenem group (22 days) than in the imipenem group (27 days; p = 0.010). The median duration of mechanical ventilation was significantly lower for doripenem (7 vs. 10 days; p = 0.034). The median ICU stay did not differ between groups (12 vs. 13 days; Table 2). Clinical cure and mortality rates did not differ between groups. Similar data were obtained in a study by LJ McGarry (2010) [52].

T. Kongnakorn et al., 2010 [51], also compared the economic aspects of the use of doripenem and imipenem in the treatment of NP. Based on clinical studies, a pharmacoeconomic model was developed that included 10 thousand patients. The response to therapy, mortality, duration of hospital treatment and ICU stay, duration of mechanical ventilation, and the incidence of P. aeruginosa resistance were assessed. In the doripenem group, costs were reduced by an average of $7,000 per patient compared with imipenem—a 95% reduction in inpatient length of stay. In addition, the incidence of P. aeruginosa resistance to doripenem was 52% lower. These results indicate that the use of doripenem has pharmacoeconomic advantages over imipenem in the treatment of NP and NP-IVL.

The Russian pharmacoeconomic study (Yu.B. Belousov et al., 2008) compared doripenem with imipenem and meropenem in the treatment of NP-IVL [53]. Pharmacoeconomic analysis was carried out using the cost minimization method, based on data from foreign randomized clinical trials.

The following pharmacoeconomic advantages of doripenem compared to meropenem have been identified: depending on the prices of drugs in the regions, the total costs of treatment in the doripenem group are 1.2–1.4 times lower than the costs of treating patients in the meropenem group (Table 3 ), which translates into savings from 1.7 to 3.5 million rubles. per 100 patients treated, regardless of regional differences in the cost of meropenem. Savings on treating patients with doripenem are due to the difference in costs for the following expense items: the use of doripenem can reduce the cost of purchasing basic antibacterial drugs by 1.4–1.9 times, which translates into savings from 1.3 to 3.1 million rubles. per 100 patients treated; the use of doripenem makes it possible to reduce the cost of hospitalization of patients by 9.2% by reducing the duration of hospitalization, which amounts to 481,841 rubles. per 100 patients.

Pharmacoeconomic advantages of doripenem compared to imipenem/cilastatin (Table 3): when conducting an analysis using hospital purchase prices in some regions, as well as the average distributor price for imipenem/cilastatin, it was shown that the cost of treatment of NP-IV with doripenem is slightly higher than the cost of treatment with imipenem/ cilastatin. However, the data obtained largely depend on the cost of imipenem. In particular, in those regions where the cost of imipenem was 800 rubles. per package, the use of doripenem is less expensive due to the lower cost of concomitant antibiotic therapy and hospitalization, on the one hand, and the almost comparable cost of the main ABT, on the other. The possible additional cost of treatment with doripenem compared to imipenem/cilastatin is approximately 4,300 rubles. per patient is justified due to the high clinical effectiveness of doripenem and the low degree of development of treatment resistance.

The results of the study show that, compared with meropenem, the use of doripenem in the treatment of NP-IVP is pharmacoeconomically effective due to the lower cost of basic antibiotic therapy and hospitalization costs. This effect is consistent regardless of regional differences in the cost of meropenem packaging. The use of doripenem compared to imipenem/cilastatin is clinically and pharmacoeconomically justified, regardless of regional differences in the cost of imipenem packaging. In the case of a lower cost per package of imipenem, the additional cost of treatment with doripenem is minimal and is justified by the low risk of developing resistance to treatment with doripenem; In the case of a higher cost of packaging for imipenem, its use compared to doripenem leads to additional costs for concomitant ABT and hospitalization of patients.

PROBLEMS OF CHOOSING CARBAPENEMIC ANTIBIOTICS IN THE LATE 90s

L.S. Strachunsky, R.S. Kozlov, O.U. Stetsyuk, O.L. Rosenson

"Clinical pharmacology and therapy", 1997; vol.6, no.4. (printed with permission of the editor)

The first antibiotic from the carbapenem group, imipenem, appeared in clinical practice in 1980. To date, more than 40 natural and synthetic compounds of this group are known, but only a few drugs are used for clinical use: imipenem, meropenem, biapenem and panipenem (the last two are used in mainly in Japan). Interest in these antibiotics has especially increased recently after the entry of a new carbapenem, meropenem, into the market in Europe (including Russia) and the United States. Its appearance has raised questions about what advantages it has over imipenem not only in vitro

, but also, above all,
in vivo
. This is especially important at the present time, since an increasing number of hospitals are switching to a formulary system for the use of drugs, and the issue of including carbapenems in them is of significant interest.

Activity spectrum

From a microbiological point of view, there are two significant differences between meropenem and imipenem (Table 1): meropenem is more active against gram-negative bacteria, and imipenem is more active against gram-positive microorganisms. The question arises, what is the clinical significance of these differences? In other words, can meropenem be used in those patients in whom imipenem was ineffective, and vice versa?

TABLE 1.

Activity of meropenem and imipenem against various pathogens (MIC90, mg/l) [1 c add.]

*

In parentheses are the results of a study of strains isolated from patients in intensive care units in 10 centers in Russia in 1995-96

Base the policy on the use of carbapenems on the absolute values ​​of their in vitro

or the results of single uncontrolled clinical studies is quite reckless, because this can lead to serious errors.
For example, it is well known that imipenem is significantly more active than meropenem against all staphylococci in general and methicillin-resistant Staphylococcus aureus
(MRSA) in particular [2]. There are also clinical observations, published in one of the world's most respected journals on antimicrobial chemotherapy, about the successful treatment of 10 out of 11 patients with infections caused by MRSA [3]. However, these data are completely insufficient to change the existing approaches to the treatment of infections caused by MRSA, so the world continues to consider MRSA as resistant to all b-lactam antibiotics (including carbapenems) and prescribe glycopeptides (vancomycin and teicoplanin) to such patients. With regard to gram-positive microorganisms, the greater activity of imipenem against pneumococci, including penicillin-resistant strains, may be of greatest clinical importance.

When treating Pseudomonas aeruginosa infection, it is necessary to take into account that meropenem is more active than imipenem. In addition, 43.8% of imipenem-resistant P. aeruginosa

remain sensitive to meropenem [4], although no controlled clinical studies have been conducted on this problem.
Meropenem's greater activity against Burkholderia (Pseudomonas) cepacia
, as this pathogen frequently causes infections in patients with cystic fibrosis [5].
in vitro
activity does not always correlate with clinical efficacy in patients with cystic fibrosis, and clinical studies of meropenem in these patients should be conducted.

Both drugs have the broadest spectrum of activity of all b-lactam antibiotics, so they are sometimes called ultra-broad-spectrum antibiotics. But, nevertheless, there are microorganisms with primary (natural) and secondary (acquired) resistance to these drugs. For example, Stenotrophomonas maltophilia, Flavobacterium

spp.
are primarily resistant to imipenem and meropenem. Secondary (acquired) resistance to carbapenems occurs very rarely. According to our data, the resistance of hospital strains to imipenem in intensive care units in Russia in 1995-1996. in P.aeruginosa
was about 7%, and resistant strains of
E.coli, K.pneumoniae, P.mirabilis, Enterobacter
spp.
was not identified [6]. Resistant strains often remain sensitive to third-generation cephalosporins. Thus, according to our data, 20 (95.2%) of 21 imipenem-resistant P. aeruginosa
remained sensitive to ceftazidime.
Resistant microorganisms (except Pseudomonas aeruginosa) have cross-resistance to imipenem and meropenem, i.e. If there is resistance to one of these drugs, the use of another is ineffective. This is largely due to the common mechanisms of resistance to imipenem and meropenem. Differences between drugs are mainly quantitative and noted only in vitro
. Thus, meropenem is hydrolyzed by one of the carbapenemases 6 times slower than imipenem, but faster than penicillin-cephalosporins [7]. However, the clinical significance of these facts has not been established.

Pharmacokinetics and pharmacodynamics

In terms of pharmacokinetic parameters (Table 2), imipenem and meropenem do not differ significantly: the half-life of both drugs is almost 1 hour; after administration of imipenem, slightly higher concentrations are created in the blood compared to meropenem; antibiotics penetrate into the cerebrospinal fluid approximately equally. The fundamental difference between meropenem is that it is not destroyed by renal dehydropeptidase I and therefore does not require the addition of an inhibitor of this enzyme, cilastatin, which is part of commercial imipenem preparations.

Table 2.

Pharmacokinetics of imipenem and meropenem [1]

The pharmacodynamics of carbapenems are similar to those of other b-lactam antibiotics. According to modern concepts, their bactericidal effect does not depend on the maximum concentration (as, for example, for aminoglycosides), but on the time of maintaining the level in the blood above the minimum inhibitory concentration (MIC) for a given pathogen. Therefore, one should not strive to ensure that the concentration exceeds the MIC by 10–15 times; it is sufficient to maintain it at a level of 2-4 times the value (Fig. 1). Increasing the concentration of b-lactams above this level does not lead to an increase in the death of microorganisms. In this regard, it is not the size of the single dose that is more important, but the frequency of administration of carbapenems.

Rice. 1.

Pharmacodynamic basis of dosing of carbapenems

An important property of carbapenems is the presence of a post-antibiotic effect against not only gram-positive, but also gram-negative microorganisms; however, there is no clinical data on the possibility of increasing the dosing interval. This is why both meropenem and imipenem are usually administered 3–4 times daily. The assertion that meropenem can be administered in a maximum daily dose of 6 g, and imipenem - only 4 g is not entirely substantiated. The results of clinical studies and extensive experience, including in Russia, show that even for the most severe patients it is enough to administer 2– 3 g imipenem per day. This, in our opinion, is also true for meropenem. An exception is patients with meningitis, who should be administered meropenem in higher doses (6 g/day). In general, according to the renowned chemotherapy specialist Professor S. R. Norrby and his co-authors K. Faulkner and P. Newell (the latter collaborators), “in clinical trials, when direct comparisons of meropenem and imipenem at the same doses were carried out, they were shown to be equally clinically effective. Taking into account these results, as well as the microbiological and pharmacokinetic data, one gram of meropenem can be considered equivalent to one gram of imipenem" [1].

Safety

From a safety point of view, the greatest importance is attached to the effect of carbapenems on the central nervous system. In patients with bacterial meningitis, meropenem has undoubted advantages due to the lack of convulsive activity characteristic of imipenem. However, in patients without meningitis, the incidence of seizures was virtually the same between meropenem and imipenem. According to generalized data, it was 0.38% with the use of meropenem (n=3911), 0.43% with imipenem/cilastatin (n=1154) and 0.37% with cephalosporins (n=1891) [8].

A second issue that is often discussed when comparing meropenem and imipenem is the incidence of nausea and vomiting. It is higher with intravenous bolus administration of imipenem; therefore, it is recommended to administer it by intravenous drip infusion over 30–60 minutes. Meropenem is less likely (0.8%) to cause nausea and vomiting, so it can be administered as an intravenous bolus. However, if we analyze widely cited data, these differences are not statistically significant (imipenem/cilastatin caused nausea/vomiting in 1.4% of patients, p = 0.203) [8], and the route of administration (boom injection over 5 min or intravenous drip infusion ) in intensive care conditions is not of fundamental importance. In children, nausea and vomiting developed in 0.8% in the meropenem group and 0.2% in the third generation cephalosporin group. An increase in ALT levels was observed in 2.7 and 1.3% of children, respectively; AST – in 2.6 and 1.4%, [9].

The statement about the greater nephrotoxicity of imipenem compared to meropenem is not convincing enough. At the same time, they overlook the fact that imipenem is used in combination with cilastatin, which, on the one hand, blocks dehydropeptidase I, and on the other, prevents the development of nephrotoxicity, which occurs with the use of b-lactam antibiotics. In addition, cilastatin is used to reduce cyclosporine-induced nephrotoxicity after heart and bone marrow transplantation [, ]. In comparative studies of meropenem and imipenem, increases in creatinine levels were observed with almost the same frequency (0.3 and 0.4%) [8].

Indications for use

Given the unique spectrum of action of carbapenems, they are widely used for a wide variety of infections. We selected those indications that are of greatest interest from the point of view of the effectiveness of monotherapy and the safety of carbapenems.

Intra-abdominal infections.

When prescribing therapy for patients with intra-abdominal infections, it is necessary to take into account their polyetiological structure: gram-negative and gram-positive microorganisms, non-spore-forming anaerobes and their associations. The spectrum of activity of carbapenems covers all these pathogens, therefore they can be considered as second-line drugs for intra-abdominal infections that developed in community settings, but as drugs of choice for hospital-acquired infections in patients after abdominal operations (peritonitis, abscesses). In controlled comparative clinical studies of meropenem at a dose of 500 mg or 1 g 3 times a day and imipenem at a dose of 500 mg 4 times a day, no significant differences in effectiveness were found, which was about 95% in each group [12]. In another controlled study in 160 patients with severe intra-abdominal infections, the effectiveness of meropenem therapy was 91%, and the combination of cefotaxime 2 g + metronidazole 500 mg 3 times a day was 100% [13].

Meningitis and brain abscess.

When treating CNS infections, the main task is not the choice of one carbapenem or another, but the solution to the question: is it necessary to use drugs from this group at all?
The main causative agents of primary bacterial meningitis are S.pneumoniae, N.meningitidis and H.influenzae
, which account for more than 80% of all cases of meningitis in children over 3 months and adults, and the proportion of different pathogens varies depending on age.
In children aged 1–3 months, the predominant pathogen is H. influenzae
. Given the etiological structure of primary bacterial meningitis, it is difficult to find a place for carbapenems in the treatment of primary meningitis; the exception is infections caused by pneumococci with reduced sensitivity to third-generation cephalosporins (the drug of choice in these cases is vancomycin).

In a multicenter study in children with bacterial meningitis without neurological impairment, the effectiveness of meropenem at a dose of 40 mg/kg 3 times a day was 79%, and cefotaxime at a dose of 75–100 mg/kg 3 times a day was 83% [14]. The incidence of hearing impairment and neurological complications was comparable in the two groups. In adult patients with meningitis caused predominantly by H. influenzae, S. pneumoniae

and
N.meningitidis
, all 23 patients recovered when treated with meropenem, and 17 (77%) out of 22 recovered when treated with cefotaxime or ceftriaxone [15]. The small size of the groups does not allow these results to be considered reliable. The comparative effectiveness of meropenem and cephalosporins for meningitis caused by penicillin-resistant pneumococci remains unclear. Two recently completed studies in children with meningitis, conducted in regions with high levels of pneumococcal resistance to antibiotics (Spain, South Africa, etc.), did not reveal any advantages of meropenem over cefotaxime or ceftriaxone: clinical effectiveness was 92% in both groups , and the eradication rate of pathogens is 99% [9].

In secondary post-traumatic meningitis or meningitis after neurosurgical interventions, the main pathogens are Pseudomonas aeruginosa and enterobacteria, staphylococci (depending on the epidemiological situation in the hospital). In these cases, as well as in secondary meningitis caused by multidrug-resistant gram-negative microorganisms, carbapenems can be considered as reserve drugs. Meropenem has been shown to be effective in a small group of patients with meningitis caused by P. aeruginosa

. [, ]

In 1996, a retrospective study from Spain was published, which noted the high effectiveness of imipenem in adults and children with multiple brain abscesses, and imipenem was used at a dose of 3-4 g/day for an average of 34 days. Seizures not associated with imipenem therapy were observed in only 1 patient with a frontal lobe abscess [18]. In acute meningitis in children, a much higher percentage of seizures was observed: in 7 (33%) out of 21, and in 6 of them, meningitis was caused by H. influenzae

type b [19]. In 1993, in a prospective study using imipenem at a daily dose of 2-4 g, seizures were recorded in 4 (0.2%) of 1951 patients, 7% of whom had concomitant central nervous system diseases and 70% had renal failure [20]. The data presented indicate that the epileptogenic activity of imipenem from a clinical point of view is insufficiently studied, but with the advent of meropenem there is no longer a need to conduct such studies. As a result, when prescribing imipenem, it is necessary to observe certain precautions (reduce the dose in case of renal failure, do not administer at a dose of more than 4 g / day, do not administer intravenously, carefully monitor patients with central nervous system damage). Meropenem is a relatively new drug, and there is little experience with its use in patients with CNS infections, so when using it, it is necessary to pay attention to adverse events from the CNS.

Neutropenic fever.

The possibility of using carbapenems for neutropenic fever deserves special attention. The high morbidity and mortality in this group of patients, especially those with severe or prolonged neutropenia, requires empirical use of broad-spectrum antibiotics. Classic treatment regimens involve a combination of two or three antimicrobial drugs, while carbapenems can be given as monotherapy. A number of clinical studies have shown equal or higher effectiveness of imipenem at a daily dose of 2–4 g compared to that of classical treatment regimens [, ]. Imipenem is currently approved for use in adult patients with neutropenic fever. For neutropenic fever in 958 patients with malignant neoplasms, the use of meropenem at a dose of 1 g 3 times a day was comparable in effectiveness to the use of a combination of ceftazidime at a dose of 2 g 3 times a day and amikacin at a dose of 20 mg/kg/day once [23] . In a comparative study of meropenem (n=483) and the combination of ceftazidime with amikacin (n=475), the effectiveness was 56% and 52%, respectively [24]. Meropenem is not yet recommended for use in such patients, but in the future, neutropenic fever is likely to become one of the indications for its use.

Cost Analysis

When analyzing the cost, two indicators were assessed: the cost of the drug and the cost of its introduction to the course of treatment. This method allows you to estimate part of the costs of therapy without taking into account its clinical effectiveness. If the clinical efficacy of the two treatment regimens is similar, as evidenced by numerous controlled clinical trials of imipenem and meropenem, then cost analysis may be critical to drug selection. Below is an analysis of the cost of imipenem and meropenem in the treatment of peritonitis in an adult patient (Table 1).

Table 3.

Cost of imipinem (Tienam) and meropenem (Meronem) and cost of antibiotic administration

* purchase cost from manufacturers, taking into account a 10% duty, ** price list for medical services of the Smolensk Regional Clinical Hospital, 1997 *** 1 US dollar = 5850 rubles.

Table 4.

Cost of using imipinem (Tienam) and meropenem (Meronem) for peritonitis in an adult

Doses of both antibiotics are taken at the rate of 0.5 g 4 times a day for a course of treatment of 10 days. The only difference was the method of drug administration: imipenem in the form of intravenous infusions, and meropenem in the form of intravenous injections. The cost of meropenem and its intravenous bolus for the treatment of peritonitis in an adult patient is 1.3 million rubles ($222) higher than the cost of imipenem for intravenous infusion. This difference, although there is a significant difference in the cost of antibiotic administration—an intravenous infusion of imipenem for 10 days of therapy is $85.94 more expensive than an intravenous injection of meropenem—is due to the higher cost of the new carbapenem. A similar analysis of the cost of imipenem and meropenem in the treatment of a 7-year-old child weighing 25 kg showed that the cost of meropenem and its intravenous bolus administration per course of treatment was 400,000 rubles ($68) higher than the cost of imipenem and its intravenous infusion administration.

Conclusion

The advent of meropenem has significantly increased interest in carbapenems, but doctors should not consider that they have received a fundamentally new antibiotic. As can be seen from table. 5, imipenem and meropenem are very similar drugs. Experts from the independent journal The Medical Letter believe that “meropenem is a fairly expensive new parenteral antibiotic, similar to imipenem, with a possibly lower convulsant potential. Meropenem, like imipenem, can be used to treat hospital-acquired infections caused by pathogens resistant to other antibiotics. When treating intra-abdominal infections or bacterial meningitis, meropenem has no fundamental advantages over more well-known and less expensive drugs” [23]. When deciding on the choice of a carbapenem antibiotic, the main arguments should, in our opinion, be the localization of the infection (for CNS infections, preference should be given to meropenem) and the cost of the drug. As for microbiological and pharmacokinetic differences, until the results of controlled clinical trials are obtained, they cannot be decisive. We should not confuse the concepts of “monotherapy with carbapenems” and “monopoly” on their use, which will inevitably lead to the emergence and spread of resistance among microorganisms. However, carbapenems should also not be considered as “deep reserve” drugs, prescribing them only to patients in critical condition, when there is no effect from antibacterial therapy. In the future, new carbapenems with activity against MRSA and enterococci will have real advantages; a longer half-life, allowing the antibiotic to be used once a day; possibility of oral administration. However, when assessing the possibilities of their use, the decisive arguments should be the results of controlled clinical studies.

Table 5.

Comparison of imipenem and meropenem

Literature

1. Norrby S., Faulkner K., Newell P. Infect. Dis. Clin. Practice, 1997, 6, 291–303.
2. Knapp C., Ludwig M. et al. Diagn. Microb. Infect. Dis., 1997, 28, 81–86.
3. Fann W. et al. Antimicrob. Agents Chemother., 1986, 29, 26–29.
4. Iaconis JP, Pitkin DH et al. Clin. Infect. Dis., 1997, 24(Suppl. 2), S191–S196.
5. Simpson I., Hunter R., Gowan JJ Antimicrob. Chemother., 1995, 35, 707–713.
6. The state of antibiotic resistance of gram-negative pathogens of nosocomial infections in intensive care units. Interdepartmental Scientific Council on Intrabol. inf. under the Russian Academy of Medical Sciences and the Ministry of Health of the Russian Federation, Interregion. association for wedge. microbe. and antimicrobial. Chemoter., 1997.
7. Baxter IA, Lambert PA FEMS Microb. Letters, 1994, 122, 251.
8. Norrby SR et al. J. Antimicrob. Chemother., 1995, 36 (Suppl. A), 207–223.
9. Bradley JS Data on file, Zeneca, 1997.
10. Markewitz et al. Transplant., 1994, 57, 865–870.
11. Gruss E. et al. Bone Marrow Transplant., 1996, 18, 761–765.
12. Geroulanos SJ et al. J. Antimicrob. Chemother., 1995, 36 (Suppl. A), 191.
13. Huizinga WKJ et al. J. Antimicrob. Chemother., 1995, 36 (Suppl. A), 179.

>

14. Klugman KP et al. Antimicrob. Agents Chemother., 1995, 39, 1140.
15. Schmutzhard E. et al. J. Antimicrob. Chemother., 1995, 36 (Suppl. A), 85.
16. Chmelik V., Gutvirth JJ Antimicrob. Chemother., 1993, 32, 922.
17. Donnelly JP et al. Lancet, 1992, 339, 1117.
18. Asensi V. Carton J. et al. Eur. J. Clin. Microbiol. Infect. Dis., 1996, 15, 653–657.
19. Wong VK, Wright HT, Ross LA Pediatr. Infect. Dis. J., 1991, 10, 122–125.
20. Prestonik S., Classen D. et al. Annals Pharmacother., 1993, 27, 497–501.
21. Winston D., Winston G. et al. Ann. Intern. Med., 1991, 115, 849–859.
22. Rolston KV, Berkey P., Bodey G. et al. Arch. Intern. Med., 1992, 152, 283–291.
23. The Medical Letter, 1996, 38 (984), 88–90.
24. Cometta A. et al. Antimicrob. Agents Chemother., 1996, 40, 1108–1115.

Visnovki

Over the past 10 years, imipenem/cilastatin has highlighted the role of carbapenems as effective broad-spectrum monotherapy for serious bacterial infections. The main undesirable effects of imepenem/cilastatin—toxic release on the central nervous system and side effects on the side of the thyroid gland—can be avoided by maintaining it in certain patients and changing the method of administration. Meropenem, a new drug in this class of antibiotics, is better tolerated, and therefore expands the formulation of carbapenems for the treatment of meningitis and allows the dose to be increased to 6 g / day. At that time, when concern about the resistance to antibiotics increases, the activity of carbapenems is no longer even high.

Prepared by Bogdan Boris

Evidence of the use of carbapenems in pediatrics

Randomized, consistent studies of more than 1000 infants and children demonstrated that the intervention was as effective and well tolerated as cefotaxime and ceftriaxone for treatment of meningitis, and effective, as a combined regimen based on cefotaxime for the treatment of various other infections, does not languages ​​from the central nervous system (Bradley JS et al., 1996). There are no indications for consolidation in children over 3 months in most countries, and the drug is approved for consolidation.

In the United States, imepenem/cilastatin has no indication for the treatment of infections in children under 12 years of age, although in other countries the drug can be administered to children over 3 months. To date, no major pediatric studies on imipenema/cilastatin have been published, Nalin and Jacobsen (1987) reported their findings on the treatment of 61 children: 9 patients (15%) went to trial (as a side effect of the drug), although in 6 of them The judges were careful even before the drug was administered.

Carbapenem has no indication for use in newborns and there is no data on the effectiveness of the measure. Pharmacokinetic studies of Vikonane for meropenem demonstrated improved volume distribution and lower elimination rates, which is explained by the physiological characteristics of this group of patients. Single doses that were well tolerated in the study population were doses of 10, 20 and 40 mg/kg.

Two recent articles reported evidence of the impeachment's imprisonment. In a retrospective study, Stuart et al. (1995) reported their data on 80 silent creatures. Only 2 patients suffered from suicide, both of whom had little information about the history of suicide before treatment. However, in a study of 53 silent animals (Scharf J. et al., 1994), trials were observed in 6 patients, and pathological changes in electroencephalograms were recorded in 10 other patients.