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Biomedical subjects

K Fuursted

Publications and source records attributed to K Fuursted.

At least 19 recordsLinked to original sources

Penicillin pharmacodynamics in four experimental pneumococcal infection models.

Clinical and animal studies indicate that with optimal dosing, penicillin may still be effective against penicillin-nonsusceptible pneumococci (PNSP). The present study examined whether the same strains of penicillin-susceptible pneumococci (PSP) and PNSP differed in their pharmacodynamic responses to penicillin by using comparable penicillin dosing regimens in four animal models: peritonitis, pneumonia, and thigh infection in mice and tissue cage infection in rabbits. Two multidrug-resistant isolates of Streptococcus pneumoniae type 6B were used, one for which the penicillin MIC was 0.016 microg/ml and the other for which the penicillin MIC was 1.0 microg/ml. Two additional strains of PNSP were studied in the rabbit. The animals were treated with five different penicillin regimens resulting in different maximum concentrations of drugs in serum (C(max)s) and times that the concentrations were greater than the MIC (T(>MIC)s). The endpoints were bacterial viability counts after 6 h of treatment in the mice and 24 h of treatment in the rabbits. Similar pharmacodynamic effects were observed in all models. In the mouse models bactericidal activity depended on the T(>MIC) and to a lesser extent on the Cmax/MIC and the generation time but not on the area under the concentration-time curve (AUC)/MIC. Maximal bactericidal activities were similar for both PSP and PNSP, being the highest in the peritoneum and blood (approximately 6 log10 CFU/ml), followed by the thigh (approximately 3 log10 CFU/thigh), and being the lowest in the lung (approximately 1 log10 CFU/lung). In the rabbit model the maximal effect was approximately 6 log10 CFU/ml after 24 h. In the mouse models bactericidal activity became marked when T(>MIC) was > or =65% of the experimental time and C(max) was > or =15 times the MIC, and in the rabbit model bactericidal activity became marked when T(>MIC) was > or =35%, Cmax was > or =5 times the MIC, and the AUC at 24 h/MIC exceeded 25. By optimization of the Cmax/MIC ratio and T(>MIC), the MIC of penicillin for pneumococci can be used to guide therapy and maximize therapeutic efficacy in nonmeningeal infections caused by PNSP.

Animals↗

Pharmacodynamics of glycopeptides in the mouse peritonitis model of Streptococcus pneumoniae or Staphylococcus aureus infection.

The emergence of resistance to various antibiotics in pneumococci leaves the glycopeptides as the only antibiotics against which pneumococci have no resistance mechanism. This situation has led to a renewed interest in the use of glycopeptides. It has not yet been possible to conclude which one or more of the pharmacokinetic or pharmacodynamic (PK/PD) parameters are the most important and best predictors for the effects of treatment with glycopeptides in animal models or in humans. We used the mouse peritonitis model with immunocompetent mice and with Staphylococcus aureus and Streptococcus pneumoniae as infective organisms. A wide spectrum of different treatment regimens with vancomycin and teicoplanin was tested to study the pharmacodynamics of these drugs. In studies in which the single dose that protected 50% of lethally infected mice (ED(50)) was given as one dose or was divided into two doses, survival was significantly decreased when the dose was divided. The only statistically significant correlations between the percentage of survival of the mice after 6 days and each of the PK/PD parameters were for peak concentration (C(max))/MIC and S. aureus and for the free fraction of C(max) (C(max-free))/MIC and S. pneumoniae. For S. pneumoniae, the ED(50) for different dosing regimens increased with the number of doses given; e.g., the single-dose ED(50)s for vancomycin and teicoplanin were 0.65 and 0. 45 mg/kg, respectively, but the ED(50)s for dosing regimens with 2-h doses given for 48 h were 6.79 and 5.67 mg/kg, respectively. In experiments with 39 different vancomycin dosing regimens and 40 different teicoplanin dosing regimens against S. pneumoniae, the different PK/PD parameters were analyzed using logistic regression. The C(max-free)/MIC was one of two parameters that best explained the effect for both drugs; for vancomycin, the other important parameter was the AUC/MIC, and for teicoplanin, the other parameter was the time the free fraction of the drug is above the MIC. The effect analyzed as a function of C(max-free)/MIC disclosed thresholds with shifts from almost no effect to full effect at ratios of five to six for vancomycin and two to three for teicoplanin.

Animals↗

[Occurrence of tuberculosis among children in the area of Copenhagen 1984-1993].

This study was undertaken to describe the epidemiology, clinical manifestations and prognosis of childhood tuberculosis in Copenhagen, with special attention to differences between Danish children and children of foreign origin. Medical records for all children with tuberculosis cared for in the hospitals of the Copenhagen area 1984-1993 were reviewed. Sixty-six patients were identified. Sixteen of 20 Danish patients (80%) and 67% of foreign children had respiratory tuberculosis. Tuberculosis located in cervical lymph nodes was found only in children of foreign origin. Five patients had meningitis. The high incidence among foreign children reflects the incidence in their home countries, but poorer living conditions among ethnic minorities in Denmark may facilitate transmission of tuberculosis. Severe manifestations of tuberculosis still occur, even in a low incidence country.

Adolescent↗

A reversed-phase high-performance liquid chromatography method for the determination of cotrimoxazole (trimethoprim/ sulphamethoxazole) in children treated for malaria.

A high-performance liquid chromatography (HPLC) method was developed for the simultaneous analysis of trimethoprim (TMP), sulphamethoxazole (SMX), and acetylsulphamethoxazole (AcSMX) in small amounts of blood. The method involved precipitation with 50 microL trichloracetic acid (1M) to 125 microL plasma or serum sample. 60 microL supernatant was added to 60 microL mobile phase, modified with 50microL 1 M sodium hydroxide/mL. The mobile phase consisted of 20% acetonitrile and 80% phosphate buffer adjusted to pH 6.15. Using 125 microL of the sample, limits of quantitation were 0.1 microg/mL for TMP, 1.0 microg/mL for SMX, and 1.0 microg/mL for AcSMX. The precision of the method was 2% to 11% over the range of concentrations tested, 0.5-30 microg/mL for TMP, 5-300 microg/mL for SMX, and 2.5-150 microg/mL for AcSMX, respectively. No interference with other commonly used drugs was observed. The method is rapid, simple, specific, and sensitive enough for pharmacokinetic studies. The small amount of blood required makes it suitable for pediatric patients. The method was used to analyze samples from Tanzanian children aged 6-59 months participating in a cotrimoxazole (TMP/SMX)/chloroquine randomized trial for the treatment of uncomplicated malaria. Venous blood samples from 68 children were collected 2 hours after the first dose of TMP/SMX (4 mg/kg TMP/20 mg/kg SMX at two divided doses for 5 days) and again at treatment day 4. Individual variations in plasma concentrations of TMP, SMX, and AcSMX were considerable. The mean and SEM plasma concentrations (g/mL) of TMP, SMX, and AcSMX 2 hours after the first treatment dose were 2.0 +/- 1.0 (range 0.5-6), 53 +/- 22 (range 24-146), and 13.5 +/- 12 (range 0-65), respectively. On the fourth day the attained plasma concentrations were not significantly different from samples collected after the first dose.

Acetonitriles↗

Disseminated infection with Mycobacterium genavense: a challenge to physicians and mycobacteriologists.

In the present study we compared the clinical presentations of patients with a clinical diagnosis of AIDS and disseminated Mycobacterium genavense infection (n = 12) with those of patients with AIDS and disseminated M. avium complex (MAC) infection (n = 24). Abdominal pain was seen more frequently in the group of patients infected with M. genavense than in patients infected with MAC (P = 0. 003). Analysis of microbiological data revealed that stool specimens from patients infected with M. genavense were more often smear positive than stool specimens from patients infected with MAC (P = 0. 00002). However, M. genavense could be cultured on solid media from only 15.4% of the stool specimens, whereas MAC could be cultured from 71.4% of the specimens. Bone marrow and liver biopsy specimens yielded growth of M. genavense within a reasonably short time, allowing species identification by DNA technology. Microbiological data clearly demonstrated the importance of acidic liquid medium for primary culture, the avoidance of pretreatment and the use of additives in culture, and the necessity for prolonged incubation if M. genavense is suspected. Susceptibility testing showed that M. genavense is sensitive to rifamycins, fluoroquinolones, and macrolides, whereas it is resistant to isoniazid. Susceptibility to ethambutol and clofazimine could not be evaluated. The mean survival times of patients in the two groups were similar.

AIDS-Related Opportunistic Infections↗

Childhood tuberculosis in a Scandinavian metropolitan area 1984-93.

This study was undertaken to describe the epidemiology, clinical manifestations and prognosis of childhood tuberculosis in Copenhagen, with special attention to differences between Danish children and children of foreign origin. From 1984-93, 66 children, aged 0-14 years, in the Copenhagen area were notified for tuberculosis. More than two-thirds of the children of foreign origin, including 5 patients from Greenland, who were transferred to Denmark for treatment. A close adult contact with contagious tuberculosis was identified in only a few patients born to foreign parents, but more than one-third had travelled to their homeland within 1 y prior to diagnosis. 48 patients (73%) were reported to have only respiratory tuberculosis. Tuberculosis located in cervical lymph glands was the most frequent nonrespiratory manifestation, but was found only in children of foreign origin. Five patients had meningitis. The high incidence among foreign children reflects the incidence in their home countries, but poorer and more crowded living conditions among ethnic minorities in Denmark may also facilitate transmission of tuberculosis. Severe manifestations of tuberculosis still occur, even in a low incidence country.

Adolescent↗

Comparison of pharmacodynamics of azithromycin and erythromycin in vitro and in vivo.

In this study, we determined the efficacy of various dosing regimens for erythromycin and azithromycin against four pneumococci with different susceptibilities to penicillin in an in vitro pharmacokinetic model and in a mouse peritonitis model. The MIC was 0.03 microg/ml, and the 50% effective doses (determined after one dose) of both drugs were comparable for the four pneumococcal strains and were in the range of 1.83 to 6.22 mg/kg. Dosing experiments with mice, using regimens for azithromycin of one to eight doses/6 h, showed the one-dose regimen to give the best result; of the pharmacodynamic parameters tested (the maximum drug concentration in serum [Cmax], the times that the drug concentration in serum remained above the MIC and above the concentration required for maximum killing, and the area under the concentration time curve), Cmax was the best predictor of outcome. The bacterial counts in mouse blood or peritoneal fluid during the first 24 h after challenge were not correlated to survival of the mice. The serum concentration profiles obtained with mice for the different dosing regimens were simulated in the in vitro pharmacokinetic model. Here as well, the one-dose regimen of azithromycin showed the best result. However, the killing curves in vivo in mouse blood and peritoneal fluid and in the vitro pharmacokinetic model were not similar. The in vitro killing curves showed a decrease of 2 log10 within 2 and 3 h for azithromycin and erythromycin, respectively whereas the in vivo killing curves showed a bacteriostatic effect for both drugs. It is concluded that the results in terms of predictive pharmacodynamic parameters are comparable for the in vitro and in vivo models and that high initial concentrations of azithromycin favor a good outcome.

Animals↗

Duration and clinical relevance of postantibiotic effect in relation to the dosing interval.

The influence of half-life on the postantibiotic effect (PAE) of tobramycin against Pseudomonas aeruginosa and Staphylococcus aureus was investigated during one dosing interval. Tobramycin half-lives of 0.5 to 2.5 h were simulated in an in vitro model, and the PAE was determined by an enzymatic inactivation method at different time points, i.e., when the tobramycin concentrations were 20x, 5x, and 1x the MIC. At the time point during therapy when the tobramycin concentrations had declined to 1x the MIC, at a tobramycin half-life of 0.5 h, the times of the PAEs were approximately 0.7 and 1.7 h for P. aeruginosa and S. aureus, respectively, and the PAE disappeared completely at half-lives corresponding to those found in humans (i.e., 2 to 2.5 h). The PAE itself cannot be fully explained by the presence of free intrabacterial tobramycin or the emergence of resistant subpopulations. The explanation for the disappearance of the PAE during the dosing interval may therefore be explained by the repair of sublethal damage. Since the standard method of determining the PAE in animal models is somewhat different from the method used for measurement of the PAE in vitro, the conditions under which the PAE is measured in vivo were also simulated in the in vitro model. This resulted in PAEs longer than those found by the standard method of obtaining in vitro PAE measurements. We conclude that the PAE of tobramycin, as determined by conventional in vitro methods, has virtually no clinical importance. PAEs determined in vivo may have some clinical relevance, but they are probably primarily caused by sub-MIC effects.

Animals↗

Evaluation of the post-antibiotic effect of six anti-mycobacterial agents against Mycobacterium avium by the Bactec radiometric method.

We compared and evaluated the duration of the post-antibiotic effect (PAE) of six anti-mycobacterial agents (ethambutol, isoniazid, rifampicin, amikacin, ciprofloxacin and clarithromycin), alone and in combination, against ten strains of Mycobacterium avium. PAE was determined by conventional viable counting and the Bactec growth system, analysed by the T100 value (the time to produce a cumulative growth index of 100). A 2 h exposure to the drug did not induce significant killing. Thus, comparison of regrowth could be evaluated without the potential need to adjust viable counts. The correlation of duration of PAE between the viable count method and the T100 Bactec method was excellent (r = 0.94). No significant PAE (< 8 h) was induced using sub-inhibitory drug concentrations or with ethambutol or isoniazid alone. Rifampicin (20-41 h) and amikacin (8-36 h) demonstrated consistent and extended PAEs, while ciprofloxacin (1-15 h) and clarithromycin (2-10 h) displayed variable PAE activities. Different three-drug combinations (all including ethambutol) displayed variable results with a combination of ethambutol, isoniazid and rifampicin being the most effective combination for extending the PAE (> or = 8 h) which was observed in half the strains tested. It was concluded that the T100 Bactec method is highly suitable for evaluating PAE against M. avium, producing a definitive result in 5 days.

Amikacin↗

Evaluation of bactericidal activity and lag of regrowth (postantibiotic effect) of five antiseptics on nine bacterial pathogens.

Lag of regrowth or postantibiotic effect (PAE) relates to suppression of bacterial regrowth following short exposure to an antimicrobial agent. A delay in regrowth has not yet been studied for antiseptics to any great extent. We therefore examined and compared the lag of regrowth and the bactericidal activity of five antiseptics (chloramine T, chlorhexidine, povidone-iodine, phenoxyethanol and mandelic-lactic acid) against nine bacterial pathogens. Delay in regrowth was determined by application of two concentration-time schedules: a test concentration at the MBC with a contact time of 1 h or using fixed suboptimum concentration of each antiseptic for 2 min (optimum concentrations sterilized the culture, impeding assessment of regrowth) followed by a neutralization-dilution step and subsequent viable counting to follow bacterial regrowth. Each antiseptic displayed a different spectrum of activity in terms of MIC or MBC, bactericidal effect and lag of regrowth. The delay in regrowth varied from 0 to 5.7 h with only a few discrepancies between the two treatment schedules. Mandelic-lactic acid and chloramine T induced a significantly longer lag as compared with the other agents, whereas phenoxyethanol produced the shortest lag values. No significant correlation between the killing rate and the lag of regrowth could be demonstrated. Information on bactericidal activity, as well as lag of regrowth, could be a useful screening method for the efficacy of antiseptics. Moreover, data on lag of regrowth could contribute to the choice of antiseptic and guide in determining the optimum interval between repeated applications of antiseptics.

Anti-Infective Agents, Local↗

Comparison of the effect of cefepime with four cephalosporins against pneumococci with various susceptibilities to penicillin, in vitro and in the mouse peritonitis model.

The purpose of this study was to compare the effect, both in vitro and in vivo, of cefepime with those of four other cephalosporins, namely ceftriaxone, cefotaxime, cefuroxime and cephalothin, against penicillin-resistant pneumococci. One hundred pneumococcal strains, 31 penicillin-susceptible, 30 penicillin-intermediate-resistant and 39 penicillin-resistant pneumococci, were used in MIC studies. Time-kill experiments were carried out for four strains. In the mouse peritonitis model, the dose that gave protection to 50% of mice challenged with a lethal dose of pneumococci (ED50) was determined for three pneumococci and five cephalosporins. The MICs of all five cephalosporins and penicillin correlated significantly with each other. In vitro, the most potent cephalosporins against pneumococci were cefotaxime, ceftriaxone and cefepime, followed by cefuroxime and cephalothin. In time-kill experiments, carried out for four pneumococci, no differences were found in the killing effect of these five cephalosporins in relation to MICs. In the mouse peritonitis model, there was no significant correlation between log(MIC) and log(ED50) for the five cephalosporins against three pneumococci (Spearman's rho = 0.39, P = 0.16). However, if the values for cefepime against the three pneumococci were excluded, there was a significant correlation for the remaining four cephalosporins (Spearman's rho = 0.62, P = 0.04). For all three pneumococci, the ED50s of cefepime were lower than expected from the MICs. It was not possible to explain this beneficial difference in the effect of cefepime in terms of in-vitro bactericidal activities, serum protein binding or pharmacodynamic parameters.

Animals↗

Distribution of serotypes, IS901 and a 40 kDa protein in Mycobacterium avium complex strains isolated from man and animals in Denmark.

The aim of the present study was to characterize all strains of the Mycobacterium avium complex isolated in Denmark in 1993. A total of 141 M. avium complex strains (86 from man, 38 from animals, and 17 from peat) were analysed by serotyping, ELISA specific for a 40 kDa protein, and IS901-specific PCR. Serotype analysis showed that the most frequent serotypes among human strains were serotype 4 (27%) and serotype 6 (19%), which differs from an earlier survey where serotype 1 was most prevalent. The most frequent serotypes in animals were serotype 2 (53%) and serotype 6 (13%), whereas the most prevalent serotypes among strains isolated from peat were serotype 4 (29%) and serotype 9 (18%). There was a concurrent appearance of IS901 and p40 in all strains. Only M. avium complex strains isolated from animals, and belonging to serotype 1 or serotype 2, contained the IS901/p40 markers. The different distribution of serotypes of M. avium complex strains in animals and man, and the presence of IS901/p40 exclusively in animal strains, suggests that transmission of M. avium from animals to man is not of significance in Denmark.

Animals↗

Comparative study of bactericidal activities, postantibiotic effects, and effects of bacterial virulence of penicillin G and six macrolides against Streptococcus pneumoniae.

In this report, we present MIC, bactericidal activity, postantibiotic effect (PAE), and in vivo infectivity data for postantibiotic-phase pneumococci. We compared and evaluated penicillin G and six macrolides, erythromycin, azithromycin, clarithromycin, dirithromycin, roxithromycin, and spiramycin, against 10 strains of pneumococci with various levels of susceptibility to penicillin. All of the agents, except azithromycin, exhibited a bactericidal effect (a > or = 3 log10 decrease in the number of CFU per milliliter) after 4 h of exposure to a concentration equal to 10 times the MIC, displaying the following hierarchy: spiramycin = penicillin G = erythromycin = dirithromycin = clarithromycin = roxithromycin > azithromycin. The bactericidal rate of penicillin G was significantly lower for resistant strains (MIC, > or = 2 microg/ml), while bactericidal rates of macrolides were unaffected by penicillin susceptibility. A PAE was induced in all of the strains by all of the antibiotics after exposure for 1 h to a concentration equivalent to 10 times the MIC. The mean duration of PAEs varied between 2.3 and 3.9 h, showing the following hierarchy: spiramycin = dirithromycin = clarithromycin = erythromycin = roxithromycin > azithromycin > penicillin G. Virulence studies were performed with immunocompetent mice by intraperitoneal inoculation of virulent, penicillin-susceptible serotype 3 pneumococci which had been pre-exposed to penicillin G or a macrolide for 1 h. A significant decrease in the virulence of postantibiotic-phase pneumococci was induced only by erythromycin, azithromycin, dirithromycin, and spiramycin, displaying 5.9-, 7.1-, 4.2-, and 3.6-fold increases in the 50% lethal dose (LD50) compared to a control suspension, respectively. No significant correlation could be demonstrated between the LD50 and the MIC, bactericidal activity, or PAE duration. These results suggest that antimicrobial interaction with host defenses in terms of virulence might be a significant parameter that could influence the drug or drug regimen of choice.

Animals↗

Postexposure factors influencing the duration of postantibiotic effect: significance of temperature, pH, cations, and oxygen tension.

The purpose of the present study was to assess and compare the impacts of various postexposure conditions on postantibiotic effect (PAE). PAEs were induced in Staphylococcus aureus and Escherichia coli by exposing the organisms to different antibiotics (penicillin G, ampicillin, erythromycin, ciprofloxacin, and gentamicin) at 5 or 10 times the MIC in plain Mueller-Hinton broth for 1 h at 35 degrees C. Regrowth was determined by measuring the viable counts after drug removal by a 10(-3) or 10(-4) dilution procedure under various postexposure conditions (incubation temperatures at 20, 25, 30, or 35 degrees C; growth under shaken, unshaken, anaerobic conditions; pH 6.0, 7.4, or 9.0; and with sodium chloride concentrations at 0, 1, 3, or 6%). PAE increased in response to a decrease in incubation temperature from 35 to 20 degrees C, and a significant correlation between bacterial generation times and duration of PAEs (r2, 0.82 to 0.97) was demonstrated. The duration of PAE was also modified by the pH in the regrowth medium. PAE increased considerably for S. aureus at pH 6.0 and 9.0 compared to that at pH 7.4 after induction with penicillin G, and with gentamicin the PAE against S. aureus recovering at pH 6.0 also increased considerably. A high concentration of sodium chloride in the regrowth medium produced the most extensive changes in PAE except for that against E. coli induced by ampicillin. PAE increased significantly in response to increased salinity. No recovery even after overnight incubation was detected for S. aureus after preexposure to penicillin, ciprofloxacin, or gentamicin. Only minor changes in the duration of PAE were observed in relation to recovery oxygen tension. It is concluded that many postexposure factors have a profound effect on the duration of PAE.

Anti-Bacterial Agents↗

Activities of vancomycin and teicoplanin against penicillin-resistant pneumococci in vitro and in vivo and correlation to pharmacokinetic parameters in the mouse peritonitis model.

The activities of glycopeptides against pneumococci were studied in vitro and in vivo. The MICs of two glycopeptides, vancomycin and teicoplanin, in different media against 10 strains of pneumococci with different susceptibilities to penicillin were determined. The MICs of teicoplanin were four times lower than those of vancomycin in Mueller-Hinton media supplemented with 5% blood, but the MICs were similar in mouse and human sera supplemented with 5% blood. The serum protein binding levels in mouse and human sera were 90% for teicoplanin in both and 25 and 35%, respectively, for vancomycin. The MICs for vancomycin and teicoplanin were only correlated in human serum (P < 0.001). The single doses giving protection to 50% of the animals in the mouse peritonitis model after a lethal challenge of pneumococci, the ED50s, were similar for vancomycin and teicoplanin, between 0.1 and 1 mg/kg of body weight for all 10 strains. The log ED50s were significantly correlated only to the log MICs of teicoplanin determined for mouse serum with 5% blood (P = 0.01) and to the log MICs of vancomycin determined by the E test (P = 0.03). Among the pharmacokinetic parameters analyzed at the ED50s, the most constant parameter was the time for which the drug concentration exceeded the MIC (T(>MIC)) when each drug was considered separately; however, when both drugs were considered together, the maximum concentration of drug in serum (Cmax) varied the least. This indicates that both these parameters are of importance for predicting the effect of the drugs. We conclude that the effect of glycopeptides was not influenced by the penicillin resistance of the pneumococci, either in vitro or in vivo, and that the superior activity of teicoplanin over that of vancomycin in vitro was abolished in vivo, an effect which probably was due to the high serum protein binding of teicoplanin. Both the pharmacokinetic parameters T(>MIC) and Cmax are important predicting the effect of glycopeptides, but the pharmacodynamics of glycopeptides are still not completely elucidated.

Animals↗

[Infections with mycobacteria other than M. tuberculosis in children].

We reviewed case records of 22 children who were diagnosed as having nontuberculous mycobacterial infection. All children were previously healthy. In 20 cases the infection presented as cervical lymphadenitis. The patients were between ten months and 14 years old, and two thirds were between 13 and 36 months old. The majority (74%) were girls. Mycobacterium avium/intracellulare was isolated most frequently (55%). The report describes the diagnosis and treatment of childhood mycobacterial cervical adenopathy. All patients except one were treated surgically. We found considerable differences in both preoperative and operative management. When excision of the lymph node (as opposed to needle biopsy) was performed, diagnosis could be made earlier and repeated surgical procedures could be avoided.

Child, Preschool↗

In vitro activity of six macrolides, clindamycin and tetracycline on Streptococcus pneumoniae with different penicillin susceptibilities.

A collection of 99 clinical isolates of Streptococcus pneumoniae, chosen due to their different susceptibilities to penicillin, were investigated with respect to their susceptibility to the macrolides azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, spiramycin, and to clindamycin and tetracycline by the agar dilution method. We found complete cross resistance among the macrolides. The pneumococci were either susceptible, MIC < or = 0.5 micrograms/ml, or resistant, MIC > or = 16 micrograms/ml, to the tested macrolides, giving a bimodal distribution. In addition, complete cross resistance was observed between clindamycin and macrolides. Pneumococci resistant to macrolides were also resistant to tetracycline, and 26% of the macrolide-susceptible strains were tetracycline resistant.

Anti-Bacterial Agents↗