Penicillin-resistant Streptococcus Pneumoniae Research Articles

Clinical aspects and cost of invasive Streptococcus pneumoniae infections in children: resistant vs. susceptible strains

Invasive Streptococcus pneumoniae infections in children are associated with serious consequences in terms of morbidity and mortality. The main objective of the study was to determine if invasive infections caused by penicillin-resistant Streptococcus pneumoniae (PRSP) differed in clinical presentation, outcome, risk factors, or cost from those caused by penicillin-susceptible strains (PSSP) in children. All patients aged 18 or less with invasive Streptococcus pneumoniae infections admitted to two teaching hospitals in Montreal between 1989 and 1998 were included in the study. We present a case–control study in which for each index case of PRSP, 3 controls with PSSP infections were matched for age, sex, and site of infection. One hundred and forty-four patients were included in the analysis (36 cases, 108 controls). There was no difference between the two groups in terms of initial clinical presentation (vital signs, laboratory results) or total length of stay. Mortality was 2.7% in both groups. Hospital antibiotic cost was higher in the PRSP group (211 Canadian dollars (CAD) vs. 74 CAD; P=0.02). Antibiotic consumption in the preceding month was significantly associated with PRSP infection. Underlying diseases or day-care attendance were not shown to be significant risk factors for acquiring invasive PRSP infection. There were no differences between invasive infections caused by PRSP and PSSP in terms of clinical presentation, morbidity or mortality in a paediatric population.

Evaluation of T-3811ME (BMS-284756), a new des-F(6)-quinolone, for treatment of meningitis caused by penicillin-resistant Streptococcus pneumoniae in rabbits.

T-3811ME (BMS-284756) is a new des-F(6)-quinolone with high levels of activity against gram-positive bacteria, including penicillin-resistant Streptococcus pneumoniae (PRSP) strains. T-3811, the free base of T-3811ME, exhibited potent activity against 28 clinical strains of PRSP isolated clinically (MIC at which 90% of the isolates tested are inhibited, 0.0625 microg/ml). After the intravenous dosing of T-3811ME (20 mg/kg of body weight as T-3811) in rabbits with meningitis caused by PRSP, the area under the concentration-time curve (AUC) of T-3811 in cerebrospinal fluid (CSF) was 5.79 microg. h/ml and was 4.5-fold higher than that of T-3811in the CSF of rabbits without meningitis. In addition, the AUC/MIC for T-3811ME (20 mg/kg as T-3811) in CSF was 185, which was 4.3-fold higher than that for ceftriaxone (administered intravenously at 100 mg/kg). After the administration of any dose of T-3811ME (5, 10, and 20 mg/kg as T-3811), the viable cell counts in CSF decreased in a dose-dependent manner. In particular, after dosing of 20 mg/kg (as T-3811), the viable cell counts in CSF were significantly less than those in the nontreated group (P < 0.01). By histopathological evaluation, 6 h after the administration of T-3811ME (20 mg/kg as T-3811), the thickening of the cerebral meninx and the infiltration of neutrophils into the cerebral meninx were less severe in the treated group than in the nontreated group. T-3811ME (BMS-284756) may be expected to be evaluated for the management of meningitis caused by highly penicillin-resistant pneumococci.

Non-fluorinated quinolones (NFQs): new antibacterials with unique properties against quinolone-resistant gram-positive pathogens.

Wide variations in the antibacterial potency and spectrum of quinolones are presumably attributable, in part, to their variable potency against the molecular targets, DNA gyrase and topoisomerase i.v. In addition, susceptibility of quinolones to resistance development via known point mutations in the target genes gyrA and parC/grlA varies depending on the effective affinities of the compounds toward the mutated targets. Using a medicinal chemistry approach, a series of 8-methoxy, Non-Fluorinated Quinolones (NFQs), with fluorine in the R6 position of the traditional fluoroquinolones replaced with hydrogen, were designed to retain potency against DNA gyrase and/or topoisomerase i.v. with point mutations in the serine-aspartate/glutamate hotspots. This resulted in compounds with antibacterial activity against a broad-spectrum of bacterial species, including multidrug-resistant gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). The efficacy of the NFQs was also demonstrated in a murine septicemia model. Furthermore, the design of the NFQs resulted in lower acute intravenous (i.v.) toxicity and clastogenicity relative to their 6-fluorinated counterparts. Use of the non-fluorinated quinolone nucleus allowed exploration of new structure-activity space and generation of a series of NFQs with unique combinations of affinities toward the wild type and mutated forms of the molecular targets.

耳鼻咽喉科急性感染症における耐性菌の検討 ＰＲＳＰ，ＢＬＮＡＲを中心として

In recent years, increased incidences of penicillin-resistant Streptococcus Pneumoniae (PRSP) strains and β-lactamase-negative ampicillin-resistant (BLNAR) Haemophilus influenzae strains have been reported. We performed bacteriological studies on 29 Streptococcus Pneumoniae strains and 26 Haemophilus influenzae strains that were isolated in our outpatient department between September 1998 and August 1999.The mean age of patients from whom bacteria were isolated was 7.3 years, while 14 of the Streptococcus Pneumoniae strains and 15 of the Haemophilus influenzae strains were isolated from patients under the age of 2 years.The 29 Streptococcus Pneumoniae strains included 11 (37.9%) penicillin-insensitive strains (PISP) and 10 (34.5%) PRSP. The combination of PISP and PRSP strains thus accounted for 72.4% of the total Streptococcus Pneumoniae isolates. Those PISP and PRSP strains were exposed to various oral antibacterial agents, and FRPM, CDTR and CFPN showed excellent antibacterial activity. The 26 Haemophilus influenzae strains did not include any β-lactamase producers, but 14 (53.8%) BLNAR strains were detected, representing a high frequency. Among the tested oral antibacterial agents, CDTR and CFPN showed excellent antibacterial activity against the BLNAR strains. FRPM showed an excellent MIC distribution in relation to the Streptococcus Pneumoniae strains, but its MICs for the Haemophilus inf luenzae strains were high.Among the currently used oral antibacterial agents, CDTR and CFPN showed excellent MICs for both the PRSP and BLNAR strains.

The utility of the Pneumonia PORT prediction rule for evaluating the severity of community-acquired pneumonia in Japan. The relationship between disease severity and drug-resistant Streptococcus pneumoniae

To examine the utility of the Pneumonia PORT prediction rule for evaluating the severity of community-acquired pneumonia (CAP) in Japan, 127 consecutive patients with CAP admitted during one-year period were recruited and stratified by the rule. The relationship between CAP severity determined by the rule and drug-resistant Streptococcus pneumoniae was also investigated. The number of the patients classified into each class was 20 (15.7%) in class I, 32 (25.2%) in class II, 32 (25.2%) in class III, 31 (24.4%) in class IV, and 12 (9.4%) in class V, respectively. Risk class-specific mortality rate was 0% in class I and II, 3.1% in class III, 3.2% in class IV, and 41.7% in class V, respectively. Twenty-seven patients (21.3%) were diagnosed as pneumococcal pneumonia. In terms of penicillin-susceptibility of Streptococcus pneumoniae, 19 strains (70.4%) were penicillin-susceptible Streptococcus pneumoniae (PSSP). Five (18.5%) were penicillin-intermediate Streptococcus pneumoniae (PISP), and 3 (11.1%) were penicillin-resistant Streptococcus pneumoniae (PRSP). Highly resistant pneumococci with penicillin MIC > or = 4.0 micrograms/mL was not observed. For severity of drug-resistant pneumococcal pneumonia, 3 patients infected with PISP were classified as class IV, 2 with PISP were as class V, 2 with PRSP were as class IV, and 1 with PRSP was as class V. The patients with drug-resistant pneumococcal pneumonia were classified as high risk classes (class IV to V), however, the mortality rate was low (0%). In conclusion, the Pneumonia PORT prediction rule is effective for evaluating the severity of CAP in Japan, especially in classifying the class V patients who are related to high mortality. The mortality rate of the patients with drug-resistant pneumococcal pneumonia was low.

重症ペニシリン耐性肺炎球菌性髄膜炎に対し持続的バンコマイシン脳室‐脊髄腔潅流療法が著効した１成人例

A 54-year-old woman with tympanitis admitted for confusion and high fever was found in a spinal tap to have an initial pressure of 39cm H2O. Cerebrospinal fluid (CSF) contained 141900/mm3 cells, 0mg/dl glucose, and 1004.3mg/dl protein. The causative bacterium was identified as penicillin-resistant Streptococcus pneumoniae (PRSP). Under a diagnosis of PRSP meningitis, we emplaced a lumbar drainage catheter and bolus-injected intrathecal vancomycin (VCM) 5mg/day via the catheter. Her high fever continued, however, and her consciousness waned. We emplaced an intraventricular drainage catheter and continuously infused intrathecal VCM via the catheter. VCM solution was made by adding 50mg of VCM 500ml of saline, and was infused at 4ml/hr (about 10mg/day) for 5 days. CSF cells decreased dramatically via continuous VCM infusion. In the final spinal tap, CSF contained 5/mm3 cells. Three months after onset, she was discharged with good recovery. Treatment with continuous intrathecal VCM infusion may thus be more effective in serious meningitis when the causative bacterium is resistant to multiple antibiotics.

Carriage of penicillin-resistant Streptococcus pneumoniae by children in day-care centers during an intervention program in Malmo, Sweden

An increasing incidence of penicillin-resistant Streptococcus pneumoniae (PRP) was detected in Malmo in 1994. To evaluate clonality and factors facilitating the spread of PRP among children in day-care centers (DCCs). We used phenotypic and DNA-fingerprinting methods in conjunction with epidemiologic data from the South Swedish Pneumococcal Intervention Project's investigation of 63 DCCs during a 3-year period (1995 to 1997) in the Malmo region. A questionnaire about building and hygiene standards disclosed no statistically significant risk factor for carriage of pneumococci. However, age younger than the mean age at the DCC or in the child group was positively associated with carriage. Contrary to expectations no association with the number of children, either at the DCC or in the individual groups, was found. Of 2912 investigated children 1224 (42%) were carriers of S. pneumoniae, and 373 (12.8%) were PRP carriers (MIC > or = 0.1 microg/ml). Among isolates with MIC > or = 0.5 microg/ml 9 serogroups and 30 genetic types were found. Two clones in serogroups 9 (33%) and 19 (24%) were dominant in most municipality districts, and dominance was sustained during the whole study period. The previously internationally recognized serotype 9V clone seemed to be very stable, with a single DNA type and resistance pattern during the study period. In contrast the serogroup 19 isolates and other serogroups had diverse DNA types and resistance patterns, supporting the hypothesis that DCCs have a unique microenvironment facilitating the recombination of penicillin-binding protein genes among streptococci. In five DCCs we found PRP isolates with two different serogroups but an identical genetic type, indicating that serotype shift may be a common phenomenon in DCCs. Multivariate logistic regression of risk factors disclosed that young age of the children in the child groups was a significant risk factor for carriage of S. pneumoniae.

Geographic, demographic, and seasonal differences in penicillin-resistant Streptococcus pneumoniae in Baltimore.

We examined the epidemiology of invasive penicillin-resistant Streptococcus pneumoniae (PRSP) infections among residents of the Baltimore metropolitan area from 1995 through 1997. During this period, the proportion PRSP cases increased 42%, from 5.7% to 8.1% of cases. PRSP rates were highest among persons aged <5 and > or =65 years, black patients, and urban dwellers. However, the proportion of PRSP cases was higher among white persons (10%) than it was among black persons (5%) and among residents of suburban counties (10%) versus urban counties (6%). PRSP cases were more common in November-April (8%) than they were in May-October (5%), particularly for persons aged > or =65 years (10% vs. 1%). By use of logistic regression, white race, suburban residence, and winter respiratory season were found to be independent predictors of infection with PRSP. The incidence of PRSP is increasing in Baltimore, and the seasonality of PRSP suggests that recent antibiotic use, which is more common in winter months, may rapidly affect the prevalence of resistant pneumococcal infections.

Activity of non-fluorinated quinolones (NFQs) against quinolone-resistant Escherichia coli and Streptococcus pneumoniae.

The newly developed 8-methoxy, non-fluorinated quinolones (NFQs) were studied to elucidate their enzyme inhibitory activity against wild-type and mutant GyrA (Ser-83-->Trp) forms of Escherichia coli DNA gyrase. Using a DNA supercoiling inhibition assay, the NFQs were found to inhibit 50% (IC50) of the E. coli DNA gyrase activity in the 1.6-3.2 mg/L concentration range and were comparable to ciprofloxacin. However, against the GyrA (Ser-83-->Trp) mutant, the NFQs were approximately 16-fold more potent than ciprofloxacin. Antibacterial potency of the NFQs was investigated using clinical isolates of E. coli and penicillin-resistant Streptococcus pneumoniae (PRSP), including strains with reduced susceptibility to quinolones. Against 20 uncharacterized clinical isolates of E. coli, the MIC90s of the NFQs were in the 0.125-0.25 mg/L range while those of ciprofloxacin, trovafloxacin, gatifloxacin and clinafloxacin were in the 0.016-0.125 mg/L range. Against clinical isolates with characterized mutations in gyrA and parC, PGE9262932, an NFQ, was two- to eight-fold more potent than ciprofloxacin. Against 23 clinical isolates of PRSP, the NFQs (MIC90 0.031-0.125 mg/L) were more potent than ciprofloxacin, trovafloxacin, and gatifloxacin (MIC90 0.25-2.0 mg/L), and at least as potent as clinafloxacin (MIC90 0.125 mg/L). Against S. pneumoniae strains with gyrA and parC mutations, the NFQs (MIC 0.125-1.0 mg/L) were more potent than ciprofloxacin, trovafloxacin and gatifloxacin (MIC 4-32 mg/L), and comparable to clinafloxacin (MIC 0.5-1 mg/L).

Measuring and interpreting associations between antibiotic use and penicillin resistance in Streptococcus pneumoniae.

Studies of the relationship between antibiotic use and resistance in pneumococci have produced conflicting results, reflecting differences in study design, setting, and measures of association used. Mathematical models of pneumococcal transmission dynamics provide a framework for interpreting and reconciling these studies. The model predicts, and the review of published studies confirms, that treatment often has little effect in increasing an individual's absolute risk of carrying/being infected by penicillin-resistant Streptococcus pneumoniae (PRSP). However, treatment substantially increases a patient's risk of carriage of/infection by PRSP relative to that of penicillin-susceptible S. pneumoniae (PSSP). The appropriate measure of association depends on the question of interest. Antibiotic use can substantially increase the prevalence of risk in the community as a whole, even when there is a small or nonexistent effect of treatment on the absolute risk that a treated individual will carry a resistant organism. Recommendations for the design and analysis of future studies of antibiotic treatment and pneumococcal resistance are proposed.

A Critical Review of Oxazolidinones: An Alternative or Replacement for Glycopeptides and Streptogramins?

To review the available data on the oxazolidinones linezolid and eperezolid. Published reports were obtained by searching MEDLINE for articles published between 1992 and 2000, inclusive. References of published papers were also obtained and reviewed. Abstracts from scientific proceedings were reviewed. Due to the limited data available regarding these agents, the criteria for study inclusion were not restrictive. The oxazolidinones (eg, linezolid) are a new antimicrobial class with a unique mechanism of action. They are active against resistant Gram-positive cocci including methicillin-susceptible and -resistant Staphylococcus aureus (MRSA), methicillin-susceptible and -resistant Staphylococccus epidermidis, vancomycin-resistant enterococci (VRE) and penicillin-resistant Streptococcus pneumoniae (PRSP). Linezolid is active against anaerobes and displays modest activity against fastidious Gram-negative pathogens such as Haemophilus influenzae, but is not active against Enterobacteriaceae. Linezolid is available both orally and parenterally, and has a bioavailability of 100%. Clinical trials comparing linezolid with standard therapy have demonstrated similar bacteriological and clinical cures rates to standard therapy in community- and hospital-acquired pneumonia, uncomplicated and complicated skin and soft tissue infections, and infections caused by MRSA and VRE. Adverse effects have been minor and infrequent; however, platelets should be monitored in patients who have received more than two weeks of linezolid therapy. It is expected that these agents will have a bright future due to their excellent spectrum of activity against antibiotic-resistant Gram-positive organisms, such as MRSA, VRE and PRSP, and their excellent bioavailability. The oxazolidinones represent a new class of antimicrobials with a unique mechanism of action. They have excellent activity against susceptible and resistant Gram-positive organisms such as MRSA, methicillin-susceptible S epidermidis, VRE and PRSP, and a good adverse effect profile; they can be administered both intravenously and orally. Their potential use in Canada may be as an intravenous and oral alternative to glycopeptides and streptogramins.

ChemInform Abstract: Synthesis and Antibacterial Activities of Novel C(3)-Aminopyrimidinyl Substituted Cephalosporins Including Against Respiratory Tract Pathogens.

The variety of cephalosporins 1 and 2 which possessed C(3)-aminopyrimidinyl substituents were prepared and evaluated for their antibacterial activities. They exhibited excellent in vitro activities especially against respiratory tract pathogens such as penicillin resistant Streptococcus pneumonia, Moraxella catarrhalis and Haemophilus influenza.

The prevalence and clonal diversity of penicillin-resistant Streptococcus pneumoniae in Kuwait.

Penicillin-resistant Streptococcus pneumoniae (PRSP) is widespread all over the world, including countries previously free of PRSP. This study was undertaken to determine the prevalence, the common serotypes and the clonality of PRSP isolated over a period of 1 year, from various clinical samples from three major hospitals in Kuwait. Strains were identified by standard methods and their antibiotic susceptibility was determined by the agar dilution method. The clonality of the isolates was determined by repetitive extragenic palindromic sequence polymerase chain reaction (REP-PCR) genomic profiling and pulsed field gel electrophoresis (PFGE). Serotyping was done by Quellung reaction using specific antisera. We found that 55% of the S. pnuemoniae were resistant to penicillin (46% and 9% exhibited intermediate and full resistance, respectively). Nearly 41% were resistant to sulfamethoxazole-trimethoprim, 9% to cefotaxime and ceftriaxone, 15% to amoxycillin-clavulanate, 17% to cefuroxime, 77 % to cefaclor, and 14% to clindamycin. The commonest serotypes among the PRSPs were 6A, 6B, 14, 19F, 23F and nontypable. PFGE and REP-PCR patterns showed a large diversity of genetic clones of the PRSP. Serotypes 6B, 14, 19F and 23F were more clonally related than the others. Our data showed that the prevalence of PRSP was high, the serotypes were diversified and different genetic clones make up the population of circulating PRSP in Kuwait.

Comparative In vitro activities of daptomycin and vancomycin against resistant gram-positive pathogens.

The in vitro activity of daptomycin against 224 current gram-positive clinical isolates including vancomycin-resistant Enterococcus faecium (VREF), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus spp. (MRSS), and penicillin-resistant Streptococcus pneumoniae (PRSP) was evaluated. The MICs at which 90% of isolates are inhibited for daptomycin and vancomycin, respectively, were as follows: MRSA, 1 and 2 microg/ml; MRSS, 1 and 4 microg/ml; PRSP, 1 and 0.5 microg/ml; and VREF, 2 and >64 microg/ml. Daptomycin was bactericidal against 82% of 17 VREF isolates. The antibacterial activity of daptomycin was strongly dependent on the calcium concentration of the medium. Daptomycin was active against all gram-positive cocci tested.

Synthesis and antibacterial activities of novel C(3)-aminopyrimidinyl substituted cephalosporins including against respiratory tract pathogens

The variety of cephalosporins 1 and 2 which possessed C(3)-aminopyrimidinyl substituents were prepared and evaluated for their antibacterial activities. They exhibited excellent in vitro activities especially against respiratory tract pathogens such as penicillin resistant Streptococcus pneumonia, Moraxella catarrhalis and Haemophilus influenza.

Antimicrobial resistance of nasopharyngeal isolates of Streptococcus pneumoniae and Haemophilus influenzae from children in the Central African Republic.

To assist the Central African Republic (CAR) develop national guidelines for treating children with pneumonia, a survey was conducted to determine antimicrobial resistance rates of nasopharyngeal isolates of Streptococcus pneumoniae (SP) and Haemophilus influenzae (HI). Secondary purposes of the survey were to identify risk factors associated with carriage of a resistant isolate and to compare the survey methods of including only children with pneumonia vs. including all ill children. A cross-sectional survey of 371 ill children was conducted at 2 outpatient clinics in Bangui, CAR. In all 272 SP isolates and 73 HI isolates were cultured. SP resistance rates to penicillin, trimethoprim-sulfamethoxazole (TMP-SMX), tetracycline and chloramphenicol were 8.8, 6.3, 42.3 and 9.2%, respectively. All penicillin-resistant SP isolates were intermediately resistant. HI resistance rates to ampicillin, TMP-SMX and chloramphenicol were 1.4, 12.3 and 0%, respectively. The most common SP serotypes/groups were 19, 14, 6 and 1; 49% of HI isolates were type b. History of antimicrobial use in the previous 7 days was the only factor associated with carriage of a resistant isolate. Resistance rates were similar among ill children regardless of whether they had pneumonia. Resistance rates were low for antimicrobials recommended by the World Health Organization for children with pneumonia. We recommended TMP-SMX as the first line treatment for pneumonia in CAR because of its low cost, ease of dosing and activity against malaria.

Therapeutic effects of parenteral β-lactam antibiotics on experimental otitis media caused by penicillin-resistant Streptococcus pneumoniae in guinea-pigs

The therapeutic effects of parenteral beta-lactam antibiotics were evaluated in experimental acute otitis media caused by penicillin-resistant Streptococcus pneumoniae (PRSP) in guinea-pigs. Cefotaxime, ceftriaxone and piperacillin significantly reduced viable cell counts of PRSP in the middle ear at a dose of 50 mg/kg bd for 3 days (P < 0.01 compared with control). The therapeutic effects of cefotaxime, ceftriaxone and piperacillin were superior to those of cefotiam and ceftazidime. These therapeutic effects reflected both in vitro activity and pharmacokinetic properties of the drugs.

Report of questionnaire survey for methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae in the Kinki District

An epidemiological investigation for methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP) was performed at 22 medical institutes in Kinki area by the questionnaire from Kinki Infection Working Group in 1998. The isolation frequencies of MRSA and PRSP, including penicillin-intermediate resistant S. pneumoniae (PISP), were 61.5 and 45.8%, respectively. As compared to the previous data of MRSA in the Kinki area of 1997, the increase of MRSA was recognized. A single infection with MRSA was 49.5% and simultaneous pathogen detected with MRSA was Candida species. On the other hand, a single infection with PRSP including PISP, was 36.4% and simultaneous pathogen with PRSP was Haemophilus influenzae. Vancomycin, teicoplanin, ST and arbekacin showed good activity against MRSA. PRSP and PISP had low activity to ampicillin and erythromycin.

Development of a new experimental model of penicillin-resistant Streptococcus pneumoniae pneumonia and amoxicillin treatment by reproducing human pharmacokinetics.

The increase of penicillin-resistant Streptococcus pneumoniae (PRSP) pneumonia results in a greater risk of antibiotic treatment failure. In vitro data are not sufficient predictors of clinical efficacy, and animal models may be insufficiently contributive, since they often use immunocompromised animals and do not always respect the human pharmacokinetics of antibiotics. We developed an experimental PRSP pneumonia model in immunocompetent rabbits, by using intrabronchial instillation of PRSP (MIC = 4 mg/liter), without any adjuvant. This reproducible model was used to assess amoxicillin efficacy by reproducing human serum pharmacokinetics following 1-g oral or intravenous administrations of amoxicillin every 8 h. Evaluation was performed by using clinical, CT scan, macroscopic, histopathologic, and microbiological criteria. Experimental pneumonia in untreated rabbits was similar to untreated severe human bacteremic untreated pneumonia; in both rabbits and humans, (i) cumulative survival was close to 50%, (ii) red or gray lung congestion and pleuritis were observed, and (iii) lung and spleen concentrations reached 5 and 4 log(10) CFU/g. A 48-h treatment resulted in a significant bacterial clearance in the lungs (1.53 versus 5.07 log(10) CFU/ml, P < 0.001) and spleen (1.00 versus 4.40 log(10) CFU/ml, P < 10(-6)) and a significant decrease in mortality (0% versus 50%, P = 0.02) in treated versus untreated rabbits. No difference was observed on macroscopic and histopathologic lesions between treated and untreated rabbits (P = 0.36 and 0.78, respectively). Similar results were obtained by using a fully penicillin-susceptible S. pneumoniae strain (MIC = 0.01 mg/liter). Our findings suggest that (i) this new model can be contributive in the evaluation of antibacterial agents and (ii) 1 g of amoxicillin three times a day may be sufficient to treat PRSP pneumonia in immunocompetent humans.

Antibiotic use and pneumococcal resistance to penicillin: the French experience

Antibiotic use and pneumococcal resistance to penicillin: the French experience