Penicillin-resistant Streptococcus Research Articles

Cross-over assessment of serum bactericidal activity of moxifloxacin and levofloxacin versus penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae in healthy volunteers

We compared the serum bactericidal activity (SBA) of moxifloxacin and levofloxacin against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae in 12 healthy volunteers. Each subject received 3 days of oral moxifloxacin 400 mg daily and levofloxacin 750 mg daily, respectively, with a 2- to 4-week washout period between regimens. Blood was drawn at 6 time points after the third dose of each antibiotic. Mean serum bactericidal titers (MSBTRs) for moxifloxacin were 4-fold higher than the mean titers for levofloxacin at each time point. For each drug, MSBTRs at each time point were the same or within one 2-fold dilution when analyzed according to the penicillin susceptibility of the strains or the sex of the subjects. The difference in SBA of the 2 drugs may have implications for the emergence of resistance and clinical outcome.

Comparative in vitro activities of carbapenem antimicrobial agents against 264 penicillin-resistant Streptococcus pneumoniae isolates from Korea

We compared in vitro activities of carbapenems against 264 penicillin-resistant Streptococcus pneumoniae (PRSP) isolates. The MIC 50/MIC 90 (μg/mL) values of imipenem, meropenem, ertapenem, and panipenem were 1/1, 0.25/0.25, 0.25/0.5, and 0.125/0.25, respectively. The susceptibility rates to imipenem, meropenem, and ertapenem were 0%, 85.2%, and 99.6%, respectively. Compared with imipenem and meropenem, ertapenem and panipenem had better in vitro activities against PRSP.

Anti-MRSA β-lactams in development, with a focus on ceftobiprole: the first anti-MRSA β-lactam to demonstrate clinical efficacy

Ceftobiprole is the first of the investigational β-lactam antibiotics with in vitro activity against methicillin-resistant staphylococci to reach and complete Phase III therapeutic trials. Its antibacterial spectrum includes methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, penicillin-resistant streptococci and many Gram-negative pathogens. It has demonstrated in vivo activity against many experimental infections caused by these pathogens. Ceftobiprole has completed Phase III clinical trials for complicated skin and skin structure infections, is being studied in Phase III pneumonia trials and has demonstrated non-inferiority compared with vancomycin in a Phase III complicated skin and skin structure infections trial, resulting in > 90% clinical cures of infections caused by MRSA. Other anti-MRSA β-lactams in therapeutic clinical trials include the carbapenem CS-023/RO-4908463 and the cephalosporin ceftaroline (PPI-0903). The future of all of these agents will depend on their clinical efficacy, safety and their ability to be accepted as β-lactams for the reliable treatment of a broad spectrum of infections, including those caused by MRSA.

P740 Changes in the catchment population -changes in the rate of penicillin-resistant Streptococcus pneumoniae strains?

P740 Changes in the catchment population -changes in the rate of penicillin-resistant Streptococcus pneumoniae strains?

全国小児科外来初診の呼吸器感染症患児より分離された<I>Streptococcus pneumoniae, Haemophilus influenzae</I>の検討 (2002～2003年)

We previously reported that penicillin-resistant Streptococcus pneumoniae (PRSP) and beta-lactamase-nonproducing ampicillin-resistant (BLNAR) were detected at a frequency of 27% and 35% in 468 strains of Streptococcus pneumoniae and 557 strains of Haemophilus influenzae isolated from pediatric patients diagnosed with respiratory infection in 20 pediatric outpatient facilities throughout Japan between November 2002 and June 2003. Here, we have added additional considerations regarding results of nasopharyngeal culture from 558 pediatric patients diagnosed with pneumonia, bronchitis, or otitis media and having no previous history of antibacterial drug administration. No significant difference was seen in the detection of S. pneumoniae or H. influenzae between nasal and oral specimens, or between patients with pneumonia, bronchitis, and otitis media. The detection of S. pneumoniae in pediatric patients 4 years old was significantly higher, however than that in pediatric patients 5 years old. The detection of H. influenzae in pediatric patients with a history of attending group childcare facilities was significantly higher than that in pediatric patients with no such history. No significant differences were seen among groups in the percentage of PSRP and BLNAR isolated among S. pneumoniae and H. influenzae strains. Nasopharyngeal culture of pediatric patients with respiratory infection yielded a higher frequency of S. pneumoniae in younger than older patients and a higher frequency of H. influenzae in pediatric patients with a history of attending group childcare facilities. The detection of resistant bacteria was considered related to other factors, such as the type of antibacterial drugs used, that are not discussed here.

High prevalence of erythromycin resistance and macrolide-resistance genes, mefA and ermB, in Streptococcus pneumoniae isolates from the upper respiratory tracts of children in the Sapporo district, Japan

Our previous study demonstrated that the frequency of penicillin-resistant Streptococcus pneumoniae (PRSP) was lower in our district than in districts in other Japanese studies. In this study, we investigated the prevalence of erythromycin resistance. The susceptibility to erythromycin and the distribution of the macrolide-resistance genes, mefA and ermB, were examined in S. pneumoniae isolates from the upper respiratory tracts of children in four cities in the Sapporo district, Hokkaido prefecture, Japan. Of the 156 isolates, 27 (17.3%) were erythromycin-sensitive, 6 (3.9%) were erythromycin-intermediately resistant, and 123 (78.9%) were erythromycin-resistant. Fifty-nine (37.8%) had the mefA gene, 89 (57.1%) had the ermB gene, and 129 (82.7%) had the mefA and/or the ermB gene. The ermB-positive isolates tended to show high resistance to erythromycin. Erythromycin-resistant isolates and the macrolide-resistance genes were often present in infants or younger children. The frequency of erythromycin-resistant isolates in the four cities was very high, ranging from 76.3% to 83. 3%, as high as the national average. Although erythromycin-resistant isolates generally tend to show cross-resistance to penicillin, the frequency of PRSP was very low in this study, as compared with other Japanese studies. Erythromycin resistance was frequently recognized not only in PRSP but also in penicillin-sensitive S. pneumoniae (PSSP) as well. In Japan, erythromycin resistance may have already become widespread, even in local areas where penicillin resistance is not especially prevalent.

Antibacterial activity and PK/PD of ceftriaxone against penicillin-resistant Streptococcus pneumoniae and β-lactamase-negative ampicillin-resistant Haemophilus influenzae isolates from patients with community-acquired pneumonia

The suitability of ceftriaxone for penicillin-resistant Streptococcus pneumoniae (PRSP) and ampicillin-resistant Haemophilus influenzae (especially beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae) and the relationship between in vitro antimicrobial activities and pharmacokinetic parameters were evaluated. The values for percentage of time above the MIC (%T>MIC) for ceftriaxone, cefotiam, flomoxef, sulbactam/cefoperazone, sulbactam/ampicillin, and meropenem, using 400 S. pneumoniae isolates and 430 H. influenzae isolates from patients with community-acquired pneumonia (CAP) from more than 100 geographically diverse medical centers during January to July of 2005, were calculated by measuring the MIC for each isolate and by using patameters of pharmacokinetics. A broth microdilution method was used to determine the MIC, using the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Meropenem showed the lowest MIC against penicillin-susceptible S. pneumoniae, followed by sulbactam/cefoperazone and ceftriaxone. Ceftriaxone had the best activity against penicillin-resistant S. pneumoniae and beta-lactamase-negative and beta-lactamase-producing ampicillin-resistant H. influenzae. Ceftriaxone was unique, showing a long elimination half-life and low MIC values where its serum level duration time was above the MIC for longer than other cephalosporins. Accordingly, the %T>MIC of ceftriaxone for a once-daily administration greatly exceeded the efficacy levels of those for the other antibacterial agents tested. Ceftriaxone has an excellent balance between in vitro antimicrobial activities and pharmacokinetic profiles; and therefore remains effective as a therapeutic agent against PRSP and BLNAR H. influenzae in CAP.

Clinical phase III open-labeled study of oral garenoxacin in patients with respiratory tract infection by penicillin-resistant Streptococcus pneumoniae

Clinical phase III open-labeled study of oral garenoxacin in patients with respiratory tract infection by penicillin-resistant Streptococcus pneumoniae

Launching of the CAN‐R Web Site –The Official Web Site of the Canadian Antimicrobial Resistance Alliance

Infectious diseases caused by antimicrobial-and antifungal-resistant pathogens are causing a global crisis. Common antimicrobial-resistant pathogens include methicillin-resistant Staphylococcus aureus (both community-associated and health care-associated), vancomycin-resistant Enterococcus faecium, penicillin-resistant Streptococcus pneumoniae, Clostridium difficile, extended-spectrum beta-lactamase-producing enterobacteriaceae, multidrug-resistant Gram-negative bacilli, multidrug-resistant Mycobacterium tuberculosis, and azole-resistant fungi. Canadian clinicians and scientists require a dynamic, turnkey resource that will help address the growing problem of antimicrobial-and antifungal-resistant infectious diseases. Access to provincial, regional and national data on antimicrobial resistance in various infections and pathogens, as well as data on antimicrobial and antifungal usage, is necessary to combat the evolution of resistance in Canada. The mission of the CAN-R Web site (Figure 1) is to create a unique, multipurpose, multidisciplinary, content-based infectious diseases and medical microbiology Web site that will address Canadian challenges and issues in antimicrobial and antifungal resistance and usage. As Co-Editors of CAN-R, our goal along with the Editorial Board (see Appendix) is to make this Web site a major entity in infectious diseases and medical microbiology in Canada over the next five to 10 years. The Web site will be used by a vast audience of Canadian clinicians who are interested in surveillance of resistant pathogens, antimicrobial and antifungal susceptibility trends, antimicrobial and antifungal utilization, new antimicrobials, and educational content, including infectious diseases treatment guidelines and mechanisms of antimicrobial action and resistance. The Co-Editors and the Editorial Board will continuously update and augment the Web site with the most current data, new studies, animations of antimicrobial action and resistance, and information on new antimicrobials. Web site users will find these resource ‘tools’ highly conducive to both learning and teaching. An important aspect of this Web site will be the availability of extensive downloads, including PowerPoint presentations on antimicrobial and antifungal resistance and usage, and infectious diseases treatment guidelines. Figure 1 Screenshot of the CAN-R Web site The major target audience of this site will be infectious diseases specialists (teaching and non-teaching), medical microbiologists, clinical and basic microbiologists, clinical pharmacists and nurses. In addition, researchers, respirologists, intensivists, urologists, hospital clinicians and surgeons will also be important audiences who will greatly benefit from this Web site. The CAN-R Web site will be a multisponsored, multiendorsed initiative with support from the Association of Medical Microbiology and Infectious Disease Canada and the Public Health Agency of Canada. The CAN-R Web site will actively seek partnerships and collaborations with existing Canadian and international organizations concerned about antimicrobial-resistant infections. We look forward to working hard along with our Editorial Board to provide Canadian physicians and scientists the latest information regarding antimicrobial and antifungal resistance and usage issues.

Epidemics of Drug-Resistant Bacterial Infections Observed in Infectious Disease Surveillance in Japan, 2001-2005

BACKGROUNDDrug-resistant bacteria have been increasing together with advancement of antimicrobial chemotherapy in recent years. In Japan, the target diseases in the National Epidemiological Surveillance of Infectious Diseases (NESID) include some drug-resistant bacterial infections.METHODSWe used the data in the NESID in Japan, 2001-2005. Target diseases were methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP) and multi-drug-resistant Pseudomonas aeruginosa (MDRPA) infections. The numbers of patients reported by sentinel hospitals (about 500) on a monthly basis were observed.RESULTSThe numbers of patients per month per sentinel hospital of 2001-2005 were 3.37-3.98 in MRSA, 0.96-1.19 in PRSP, and 0.11-0.13 in MDRPA infections. The sex ratios (male / female) of patients were 1.69-1.82, 1.34-1.43, and 1.71-2.52, respectively. More than 50% of all patients were adults aged 70 years or older in MRSA and MDRPA infections, but more than 60% were children under 10 years in PRSP infections. The number of patients per sentinel hospital in MRSA infections showed little variation between months, but evidenced a large variation in PRSP and MDRPA infections. The annual trend in the number of patients per sentinel hospital was increasing significantly for the 5-year period in MRSA and PRSP infections, but not in MDRPA infections.CONCLUSIONSWe revealed sex-age distributions of the patients reported to NESID in Japan, 2001-2005. An increasing incidence of MRSA and PRSP infections and monthly variation in PRSP and MDRPA infections were observed for the 5-year period. Extended observation would be necessary to confirm these trends and variations.

Linezolid in Children: Recent Patents and Advances

Linezolid is the first approved member of a new generation of antibiotics, the synthetic oxazolidinones, to become available, with a broad spectrum of in vitro activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Enterococcus faecium. It has an excellent bioavailability both intravenously and orally and a very good safety profile both in adults and in children. With regards to its antimicrobial action, linezolid has a predominantly bacteriostatic action, rather than a bacteriocidal effect and is active against Gram-positive bacteria that are resistant to other antibiotics. Linezolid is currently showing great promise for the treatment of multi-resistant Gram-positive infections, both in the community and in a hospital setting. Clinical indications so far include skin and soft tissue infections, community-acquired or nosocomial pneumonia due to MRSA, VRE bacteremia and community-acquired pneumonia due to penicillin-resistant Streptococcus pneumoniae. We anticipate that this new generation of antimicrobial agents will provide adequate cover in the future for infections that cause significant treatment failures so far, such as VRE- associated endocarditis, bone and joint multi-drug resistant infections and possibly central nervous system infections, both in adult and children populations. Some patents on linezolid are also discussed in this review.

脾摘後に発症したペニシリン耐性肺炎球菌による髄膜炎の一症例

脾摘後に発症したペニシリン耐性肺炎球菌による髄膜炎の一症例

Ceftobiprole – a case study

Ceftobiprole medocaril is a cephalosporin prodrug that is under investigation for treatment of complicated skin and skin-structure infections (cSSSIs) due to methicillin-resistant Staphylococcus aureus (MRSA) and hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia due to suspected or proven MRSA. Ceftobiprole was designed to bind the penicillin-resistant targets in Gram-positive bacteria, resulting in potent bactericidal activity against methicillin-resistant MRSA and penicillin-resistant Streptococcus pneumoniae (PRSP). In microbiological studies, ceftobiprole has demonstrated a broad-spectrum profile, with activity against many Gram-positive bacteria and a variety of important pathogenic Gram-negative bacteria. Ceftobiprole medocaril is being studied in Phase III clinical trials for cSSSI, HAP and hospitalised community-acquired pneumonia (hCAP). Top-line Phase III results in the first cSSSI study (STRAUSS 1) showed a high cure rate and good tolerability. The second cSSSI trial (STRAUSS 2) is targeting infections caused by Gram-positive and Gram-negative bacteria, and includes patients with diabetic foot infections. Ceftobiprole is expected to combine the well-established advantages of the cephalosporin antibiotic class with an enhanced spectrum of action, including against resistant Gram-positive bacteria.

In vitro Activities of Oral Cephem and Telithromycin Against Clinical Isolates of Major Respiratory Pathogens in Japan

The in vitro antibacterial activities of oral cephem antibiotics and ketolide telithromycin against major respiratory pathogens possessing β-lactam-resistant mutations (within the pbp gene) and/or macrolide-resistant genes (erm and mef) were examined in clinical isolates collected at 66 institutes in all over the Japan between 2002 and 2003. Telithromycin showed the strongest antibacterial activity against methicillin-susceptible Staphylococcus aureus strains with and without macrolide-resistant genes, such as ermA or ermC gene. All the cephem antibiotics showed potent antibacterial activity against Streptococcus pyogenes, with minimum inhibitory concentrations (MICs) of 0.015 mg/L or lower. Cefdinir had a much higher MIC90 against genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) than cefditoren and cefcapene (8 mg/L cefdinir vs. 1 mg/L cefditoren and cefcapene). The majority of gPRSP harbored either ermB or mefA, and the antibacterial activity of telithromycin against these strains was decreased however some susceptibility was still sustained. Cefditoren exerted the strongest antibacterial activity against β-lactamase-negative ampicillin-resistant Haemophilus influenzae, with an MIC90 of 0.5 mg/L. These results underline the importance of checking the susceptibility and selecting an appropriate antibiotic against target pathogens.

Penicillin-Resistant Streptococcus pneumoniae in Iran

Objective: To determine the prevalence of penicillin-resistant Streptococcus pneumoniae isolated from patients with community-acquired pneumococcal infections. Materials and Methods: A broth dilution method was used to determine the minimum inhibitory concentration (MIC) of penicillin and other commonly used antibiotics. 115 heavy growth or pure culture of S. pneumoniae strains were isolated from: blood 10, cerebrospinal fluid (CSF) 15, ear 5, eye 12, purulent rhinosinusitis 48, sputum 22, and pleural fluid 3. Results: Of the 115 pneumococcoal isolates, 76 (66.1%) were sensitive to penicillin while the remaining 39 (33.9%) were nonsusceptible (15.6% resistant and 18.3% intermediately resistant). Among the 25 pneumococcal isolates from sterile sites (blood 15, CSF 10), 15 (60%) were penicillin-resistant whereas among the 90 isolates from nonsterile sites, 24 (26.7%) were resistant to penicillin (<0.004). The MIC values of antibiotics tested for S. pneumoniae were: penicillin 0.008–4 µg/ml, chloramphenicol 0.25–32 µg/ml, erythromycin 0.008–128 µg/ml, tetracycline 0.06–64 µg/ml, vancomycin 0.03–0.5 µg/ml, azithromycin 0.016–128 µg/ml, ciprofloxacin 0.006–8 µg/ml, cefotaxime 0.007–2 µg/ml, and ceftriaxone 0.016–12 µg/ml. Conclusion: Approximately one third of S. pneumoniae isolated from the clinical specimens were nonsusceptible to penicillin in this region.

Proinflammatory activation of Toll-like receptor-2 during exposure of penicillin-resistant Streptococcus pneumoniae to -lactam antibiotics

Disease caused by penicillin-resistant Streptococcus pneumoniae (PRSP) is associated with more suppurative complications than disease caused by penicillin-susceptible S. pneumoniae (PSSP). Exposure of S. pneumoniae to beta-lactam antibiotics enhances the proinflammatory activation of human cells by pneumococci via Toll-like receptor-2 (TLR2). To test the hypothesis that penicillin resistance influences cellular TLR2 activation by beta-lactam-exposed pneumococci, we compared TLR2 induction by PSSP (MIC 0.06 mg/L) and a high-level PRSP clinical isolate (159; MIC 16 mg/L) following exposure to penicillin and cefotaxime. Both organisms were treated with penicillin or cefotaxime at and around the MIC. TLR2 signalling was measured as relative IL-8 promoter activation in transfected HeLa cells. On exposure to penicillin, log-phase PSSP and PRSP induced TLR2-proinflammatory activation at levels significantly higher than unexposed bacteria, and maximal in each case at the MIC. Transformants containing low-affinity penicillin-binding proteins (PBP) 2x, 1a and 2b exhibited stepwise resistance to cefotaxime and penicillin. TLR2 activation following penicillin treatment was dependent on an abnormal cell wall (PBP1a and 2x) and autolysis (PBP2b). High affinity PBP2x was required for this effect to be observed in log-phase pneumococci exposed to cefotaxime at the MIC. Cefotaxime-mediated TLR2 activation was not observed in lag-phase transformants exposed to sub-lethal concentrations. These data show that PRSP have similar TLR2-proinflammatory effects to PSSP when exposed to beta-lactam antibiotics but the antibiotic concentration relative to the MIC is critical. This has implications for treatment of pneumococcal disease when tissue concentrations of antibiotic are close to the MIC.

Amoxicillin is effective against penicillin-resistant Streptococcus pneumoniae strains in a mouse pneumonia model simulating human pharmacokinetics.

High-dose oral amoxicillin (3 g/day) is the recommended empirical outpatient treatment of community-acquired pneumonia (CAP) in many European guidelines. To investigate the clinical efficacy of this treatment in CAP caused by Streptococcus pneumoniae strains with MICs of amoxicillin > or =2 microg/ml, we used a lethal bacteremic pneumonia model in leukopenic female Swiss mice with induced renal failure to replicate amoxicillin kinetics in humans given 1 g/8 h orally. Amoxicillin (15 mg/kg of body weight/8 h subcutaneously) was given for 3 days. We used four S. pneumoniae strains with differing amoxicillin susceptibility and tolerance profiles. Rapid bacterial killing occurred with an amoxicillin-susceptible nontolerant strain: after 4 h, blood cultures were negative and lung homogenate counts under the 2 log(10) CFU/ml detection threshold (6.5 log(10) CFU/ml in controls, P < 0.01). With an amoxicillin-intermediate nontolerant strain, significant pulmonary bacterial clearance was observed after 24 h (4.3 versus 7.9 log(10) CFU/ml, P < 0.01), and counts were undetectable 12 h after treatment completion. With an amoxicillin-intermediate tolerant strain, 24-h bacterial clearance was similar (5.4 versus 8.3 log(10) CFU/ml, P < 0.05), but 12 h after treatment completion, lung homogenates contained 3.3 log(10) CFU/ml. Similar results were obtained with an amoxicillin-resistant and -tolerant strain. Day 10 survival rates were usually similar across strains. Amoxicillin with pharmacokinetics simulating 1 g/8 h orally in humans is bactericidal in mice with pneumonia due to S. pneumoniae for which MICs were 2 to 4 microg/ml. The killing rate depends not only on resistance but also on tolerance of the S. pneumoniae strains.

Synthesis and SAR study of novel 7-(pyridinium-3-yl)-carbonyl imidazo[5,1- b]thiazol-2-yl carbapenems

A new series of 1β-methyl carbapenems, possessing a 7-substituted imidazo[5,1- b]thiazol-2-yl group directly attached to the C-2 position of the carbapenem nucleus, was synthesized and evaluated for antibacterial activity. These compounds showed potent activities against Gram-positive bacteria, in particular methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). They also exhibited potent activity against β-lactamase-negative ampicillin-resistant Haemophilus influenzae (BLNAR).

Mutations in penicillin-binding protein (PBP) genes and in non-PBP genes during selection of penicillin-resistant Streptococcus gordonii.

Penicillin resistance in Streptococcus spp. involves multiple mutations in both penicillin-binding proteins (PBPs) and non-PBP genes. Here, we studied the development of penicillin resistance in the oral commensal Streptococcus gordonii. Cyclic exposure of bacteria to twofold-increasing penicillin concentrations selected for a progressive 250- to 500-fold MIC increase (from 0.008 to between 2 and 4 microg/ml). The major MIC increase (> or = 35-fold) was related to non-PBP mutations, whereas PBP mutations accounted only for a 4- to 8-fold additional increase. PBP mutations occurred in class B PBPs 2X and 2B, which carry a transpeptidase domain, but not in class A PBP 1A, 1B, or 2A, which carry an additional transglycosylase domain. Therefore, we tested whether inactivation of class A PBPs affected resistance development in spite of the absence of mutations. Deletion of PBP 1A or 2A profoundly slowed down resistance development but only moderately affected resistance in already highly resistant mutants (MIC = 2 to 4 microg/ml). Thus, class A PBPs might facilitate early development of resistance by stabilizing penicillin-altered peptidoglycan via transglycosylation, whereas they might be less indispensable in highly resistant mutants which have reestablished a penicillin-insensitive cell wall-building machinery. The contribution of PBP and non-PBP mutations alone could be individualized in DNA transformation. Both PBP and non-PBP mutations conferred some level of intrinsic resistance, but combining the mutations synergized them to ensure high-level resistance (> or = 2 microg/ml). The results underline the complexity of penicillin resistance development and suggest that inhibition of transglycosylase might be an as yet underestimated way to interfere with early resistance development.

Efficacy of a novel oral carbapenem, tebipenem pivoxil (TBM-PI), against experimental otitis media caused by penicillin resistant Streptococcus pneumoniae in chinchilla

An animal model of otitis media using chinchillas was developed to evaluate the efficacy of tebipenem pivoxil (TBM-PI) against experimental otitis media. Chinchillas inoculated via the transbullar approach with Streptococcus pneumoniae serogroup 6 were included in the efficacy study with TBM-PI, amoxicillin (AMX) or untreated as controls. TBM-PI resulted in survival rate of 83%, compared with 25% survival for AMX and 0% survival for controls ( p < 0.01). Quantitative cultures in the middle ear effusions at day 5 of the TBM-PI group yielded 3.5 ± 2.4 log 10 CFUs/ml. TBM-PI is a promising antibiotic for the treatment of acute otitis media.