In 2003, the United States National Committee for Clinical and Laboratory Standards (NCCLS) developed new criteria to interpret the results of the determination of sensitivity (determination of minimum inhibitory concentrations - MIC) Streptococcus pneumoniae cefotaxime and ceftriaxone.
The previous criteria were based on the values of the concentrations of these antibiotics obtained in the cerebrospinal fluid and on the data on the MIC of cefotaxime and ceftriaxone in strains of pneumococci, in which the treatment of meningitis with these drugs should be ineffective. New interpretation criteria suggest different interpretation criteria for pneumococcal strains isolated from meningitis and pneumococcal infections from a different location.
Based on the criteria previously used to interpret the results, the MPC limit values for cefotaxime and ceftriaxone for all pneumococci were less than 0.5 mg / l; 1.0 mg / L and more than 2 mg / L for sensitive, moderately resistant and resistant strains, respectively.
According to the new principles of interpretation of the results, the strains of S. pneumoniae isolated from the cerebrospinal fluid and from other loci of the body with suspected pneumococcal meningitis are classified according to previously accepted criteria, and pneumococcal strains isolated from infections of other sites using the new MPC limit values of cefotaxime and ceftriaxone: respectively less than 1, 2, more than 4 mg / ml.
In the United States, the Centers for Disease Control (CDC) analyzed the results of the determination of cefotaxime BMD for the S. pneumoniae strains obtained in the ABCs (Active Bacterial Core) study. Surveillance - Active Epidemiological Surveillance of Key Bacterial Pathogens). Program of the Emergency Infections Program (EIP) network for 1998-2001.
The main objective of this analysis was to determine the influence of new criteria for interpreting the results of the determination of the sensitivity of pneumococci on the data on the frequency of isolation of insensitive strains (resistant + moderately resistant - P + U / P) to the strains of cefotaxime and ceftriaxone S. pneumoniae.
From 1998 to 2001 (ABC / EIP Study) In 8 American states, cases of invasive pneumococcal disease were recorded. The population studied varied from 17.4 million in 1998 to 18.6 million in 2001. A case of invasive pneumococcal infection was recorded when the patient isolated S. pneumoniae from normal sterile loci of the body. The sensitivity of the isolated strains was determined in a reference laboratory in accordance with NCCLS standards.
From 3128 to 3961 strains S. pneumoniae were isolated each year from 1998 to 2001. Of these, 95.6% were invasive strains of pneumococci causing the so-called "syndromes unconscious ”, such as pneumonia with bacteremia. The number of strains isolated from meningitis varied from 4.4% in 1998 to 5.5% in 2000. When evaluating sensitivity data using previously accepted interpretation criteria, the frequency of isolation of strains insensitive (P + Y / P) to the strains of cefotaxime S. pneumoniae, which caused "meningeal syndromes", was 13.8% in 1998 and 16.7% in 2002. With meningitis, the detection rate of strains of pneumococci resistant to cefotaxime was higher.
With the use of new interpretation criteria, the frequency of classification of pneumococci isolated from "non-mengial syndromes" as insensitive (P + U / P) to cefotaxime decreased to 5.6-7.4%, while data on the resistance of S. pneumoniae strains isolated from meningitis has not changed. In general, the results of the analysis showed that after the introduction of new interpretation criteria, the frequency of classification of the strains of pneumococci as insensitive (P + U / P) to cefotaxime decreased from 52.1 to 61.2% for each year analyzed.
On the basis of the results, the authors of the analysis recommend that microbiologists include in laboratory reports for clinicians special explanations on the use of different criteria to interpret the results of the determination of the sensitivity of the strains of isolated pneumococci meningitis and with "meningitis syndromes".
When applying new criteria for interpreting the results of the determination of sensitivity to the data previously obtained in the ABC study on the MIC values of cefotaxime and ceftriaxone compared to the strains S. pneumoniae isolated in 1998-2001, the frequency of classification of pneumococcal strains as insensitive (P + Y / P) to cefotaxime decreased from 52.1 to 61.2% for each year analyzed. Although the criteria for interpretation remained unchanged for S. pneumoniae strains obtained from cerebrospinal fluid and other locus of the body suspected of pneumococcal meningitis, these isolates represent only a small fraction of all strains collected (4-5%).
The previously accepted criteria for interpreting the results of the determination of the susceptibility of S. pneumoniae were based on the data that the results of beta-lactam treatment for pneumococcal meningitis caused by strains with moderate resistance to corresponding antibiotics was significantly worse than in cases caused by susceptible isolates. However, a similar pattern has not been observed in cases of pneumococcal pneumonia, which may be due to differences in achievable levels of beta-lactam concentrations in plasma, cerebrospinal fluid and lung tissue. The concentrations of beta-lactam antibiotics in lung tissue are approximately equal to serum, but their concentrations in cerebrospinal fluid are significantly lower than in blood serum.
It should be noted that the MIC limits for penicillin for pneumococci have not been changed since penicillin sensitivity (MPC is less than 0.06 mg / ml) is used as a predictor of sensitivity to other penicillins , cephalosporins and carbapenems. In addition, the development of new criteria to interpret the results of the determination of penicillin sensitivity of the “non-household isolates” of S. pneumoniae would require the creation of specific recommendations on the use of different doses and treatment regimens for pneumococcal infections with this antibiotic.
The analysis showed that the modification of the interpretation criteria has a significant impact on the data on the resistance of pneumococci to antibiotics. Therefore, clinical laboratories, as well as organizations involved in the surveillance of antibiotic resistance of pneumococci, should pay attention to the correct interpretation of the data on the resistance of S. pneumoniae isolates isolated from various infections.
The results of the determination of sensitivity to antibiotics have a significant impact on the choice of the drug by clinicians. Modern recommendations for the treatment of pneumonia caused by penicillin-resistant pneumococcal strains offer the choice of an antimicrobial drug based on the results of the determination of sensitivity: cefotaxime, ceftriaxone, respiratory fluoroquinolone or, if the strain is resistant to third generation cephalosporins and vancomycin fluoroquinolones.
The introduction of new clinically justified criteria to interpret the results of the determination of the susceptibility of pneumococci to cefotaxime and ceftriaxone may lead to an increase in the frequency of these antibiotics for the treatment of unconscious pneumococcal infections, which may reduce the use of broad-spectrum drugs (fluoroquinolones) and slow the development of pneumococcal resistance to pneumococci..

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