ro13-9904 and Pneumococcal-Infections

BACKGROUND Despite proven efficacy of vaccinations against Streptococcus pneumoniae in preventing infection, only 70% of eligible individuals receive the vaccine in the United States. Pneumococcal bacteremia represents a form of invasive pneumococcal disease and is associated with high mortality, especially in immunocompromised patients and the elderly. Purpura fulminans is a rare complication and manifestation of disseminated intravascular coagulation and sepsis. It is exceedingly rare in the setting of pneumococcal bacteremia, particularly in immunocompetent individuals. CASE REPORT We report a generally healthy 67-year-old male with schizophrenia who refused pneumococcal vaccination. He had an intact and functional spleen with a functional immune system. The patient presented with fever and diarrhea. He subsequently progressed to develop purpura fulminans and septic shock due to S. pneumoniae bacteremia. Despite an extensive search for the primary source of infection, none could not be identified. Due to timely initiation of appropriate antibiotic therapy and aggressive supportive care in an intensive care unit, he recovered despite multi-organ failure that developed throughout his hospitalization. CONCLUSIONS We present a rare manifestation of a potentially preventable disease and emphasize the importance of pneumococcal vaccination in order to decrease the risk of developing invasive pneumococcal disease. Furthermore, we discuss etiology, diagnosis, differential diagnosis, and evidence-based management of purpura fulminans and invasive pneumococcal disease with a literature review. Purpura fulminans due to S. pneumoniae is exceedingly rare in immunocompetent patients and an unusual clinical manifestation of pneumococcal bacteremia.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Diagnosis, Differential; Humans; Male; Pneumococcal Infections; Purpura Fulminans; Shock, Septic; Streptococcus pneumoniae; Vaccination Refusal

Infectious aortitis is a rare clinical entity that most often manifests itself by an aortic aneurysm. The syphilitic or tubercular forms can be subacute. When it is caused by Salmonella sp., Staphylococcus sp. or Streptococcus pneumoniae, the aortitis is acute with alarming symptoms. Germs found in most cases are Salmonella and Staphylococcus aureus. S. pneumoniae rarely causes infectious aortitis. We report the case of a 75-year-old patient seen in an emergency setting for sudden-onset abdominal pain with fever. An abdominal angio-computed tomography (CT) scan showed a sacciform infrarenal abdominal aortic aneurysm, with an inflammatory aspect and periaortic hematoma. Surgical cure was undertaken because of the impending rupture. An interposition aortic replacement graft was implanted. Blood cultures and bacteriological study of the aortic wall isolated a S. pneumoniae. The anatomical pathology study reported fibrin clot leukocyte remodeling of the aortic wall. An intravenous antibiotic regimen was started. Several organisms, including Streptococcus, can cause infectious aortitis. We found 36 cases described in the literature in addition to our patient.

Topics: Abdominal Pain; Aged; Amoxicillin; Aneurysm, Infected; Anti-Bacterial Agents; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Aortitis; Bacteremia; Blood Vessel Prosthesis Implantation; Ceftriaxone; Combined Modality Therapy; Fever; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Male; Pneumococcal Infections; Streptococcus pneumoniae; Tomography, X-Ray Computed

Acute mastoiditis (AM) is a relatively rare complication of acute otitis media (AOM). The most common pathogens include Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus. Pneumococcal vaccination and changes in antibiotic prescribing recommendations for AOM may change the incidence of AM in the future. Diagnosis of AM can be made based on clinical presentation, but computed tomography of the temporal bone with contrast should be considered if there is concern for complicated AM. Both extracranial and intracranial complications of AM may occur. Previously, routine cortical mastoidectomy was recommended for AM treatment, but new data suggest that a more conservative treatment approach can be considered, including intravenous (IV) antibiotics alone or IV antibiotics with myringotomy. [Pediatr Ann. 2016;45(5):e176-e179.].

Topics: Abscess; Acute Disease; Anti-Bacterial Agents; Ceftriaxone; Female; Humans; Infant; Mastoid; Mastoiditis; Otitis Media with Effusion; Periosteum; Periostitis; Pneumococcal Infections; Streptococcus pneumoniae; Tomography, X-Ray Computed

To review data to determine why pneumococcal isolates appear to be increasingly resistant to cefotaxime, historically regarded as having the same in vitro susceptibility to ceftriaxone, and what this observation might imply clinically.. Literature was accessed through MEDLINE (1966-October 2007) using the MeSH terms cefotaxime, ceftriaxone, susceptibility, microbial sensitivity tests, antibiotics, pneumococcal infections, Streptococcus pneumoniae, resistance, and cephalosporin resistance. Abstracts and surveillance databases were reviewed and unpublished data were provided by state departments of health and institutions.. All articles published in the English language that were identified from the data sources were evaluated.. An experimental model of pneumococcal infection in mice conducted 2 decades ago predicted that the delta T minimum inhibitory concentration (MIC) varied less for ceftriaxone than for cefotaxime. Studies of plasma and serum concentrations show that ceftriaxone remains at a concentration above the S. pneumoniae MIC for 100% of the dosing interval at 12 hours. Types of MIC susceptibility test methods for ceftriaxone and cefotaxime used against S. pneumoniae respiratory isolates were found to be similar. Data from state and county health departments found microbiological discrepancies between ceftriaxone and cefotaxime. In areas with high rates of penicillin-resistant S. pneumoniae (PRSP), isolates were twice as susceptible to ceftriaxone versus cefotaxime. Surveillance databases consistently show differences between susceptibility of S. pneumoniae to cefotaxime versus ceftriaxone over time. MIC and pulsed-field gel electrophoresis studies suggest that phenotypic discrepancies may account for penicillin resistance. Ongoing studies are examining S. pneumoniae isolates at the molecular level to determine the basis of difference in resistance to cefotaxime and ceftriaxone.. An increase in rates of PRSP and differences in S. pneumoniae isolate susceptibility between ceftriaxone and cefotaxime emphasize the necessity for hospital laboratories to detect these changes as they occur. Clinicians should select the most appropriate agent for patients with S. pneumoniae.

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Cephalosporin Resistance; Humans; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae; Time Factors

Streptococcus pneumoniae endocarditis is most commonly associated with pneumonia. It is relatively uncommon disease but its severity makes it clinically relevant. We present a case and review of sinusitis complicated by both pneumococcal endocarditis and cavernous sinus thrombosis. Both endocarditis and dural sinus thrombosis are known complications of facial infections. To our knowledge, this is the first reported case of both S. pneumoniae endocarditis and dural sinus thrombosis complicating sinusitis. A case report and review of the literature is presented.

Topics: Adult; Cavernous Sinus Thrombosis; Ceftriaxone; Endocarditis, Bacterial; Humans; Male; Pneumococcal Infections; Sinusitis

Appropriate treatment with antimicrobials involves factors we cannot control. Factors such as interpatient variability in drug exposure, the minimum inhibitory concentration (MIC) of the infecting pathogen, and the patient's clinical status clearly affect the therapeutic response. Despite these uncertainties, we can estimate the probability of attaining a successful therapeutic outcome in the context of factors that are within our control. Chief among these are drug, dose, and the dosing interval. One way to predict the probability of a positive therapeutic outcome is through the use of an integrated pharmacokinetic-pharmacodynamic stochastic model. Pharmacokinetic-pharmacodynamic target attainment analyses using Monte Carlo simulation to integrate interpatient variability in drug exposure, drug potency, and in vivo exposure targets predictive of positive therapeutic outcomes are influencing antibacterial susceptibility breakpoints at home and abroad. The consequences of this paradigm shift are far reaching, affecting the commercial concerns of drug and susceptibility testing device manufacturers, perceptions about antimicrobial resistance, and ultimately patient care decisions.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefotaxime; Ceftriaxone; Drug Resistance, Bacterial; Humans; Models, Statistical; Monte Carlo Method; Pneumococcal Infections; Streptococcus pneumoniae

Topics: Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Child, Preschool; Fever; Haemophilus Infections; Haemophilus influenzae; Haemophilus Vaccines; Humans; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Practice Guidelines as Topic; Risk Factors; Urinary Tract Infections; Vaccines, Conjugate

We report an unusual case of Streptococcus pneumoniae sacroiliitis in a previously healthy 31-year-old woman. Six cases of pneumococcal sacroiliitis have been reported; the only two cases in adults occurred in young women in the preantibiotic era. Our patient had fever and a depressed level of consciousness, with subsequent right buttock and thigh pain. Blood cultures revealed S pneumoniae, and a bone scan showed increased tracer activity in the right sacroiliac joint. Although the cerebrospinal fluid white blood cell count was only 3/microL, culture of cerebrospinal fluid grew S pneumoniae. Our patient was successfully treated with a 6-week course of intravenous antibiotics (penicillin G after an initial week of ceftriaxone), followed by 2 weeks of oral penicillin therapy.

Topics: Administration, Oral; Adult; Arthritis, Infectious; Bacteremia; Buttocks; Ceftriaxone; Cephalosporins; Consciousness; Drug Therapy, Combination; Female; Fever; Humans; Injections, Intravenous; Pain; Penicillin G; Penicillins; Pneumococcal Infections; Sacroiliac Joint; Streptococcus pneumoniae; Thigh

A 3-day intramuscular ceftriaxone regimen was superior to a 1-day regimen in the treatment of nonresponsive acute otitis media caused by resistant Streptococcus pneumoniae. However, the effect of various regimens of intramuscular cefriaxone on the nasopharyngeal carriage of S. pneumoniae and especially that of resistant strains during and after therapy has not been thoughtfully studied.. To compare the effect of one dose and three dose intramuscular ceftriaxone regimens on the nasopharyngeal carriage of S. pneumoniae in patients with nonresponsive acute otitis media treated with these two regimens and to document the dynamics of nasopharyngeal colonization with S. pneumoniae during and after completion of these two therapeutic regimens.. In a prospective study performed during January, 1998, through September, 1999, 170 evaluable patients ages 3 to 36 months with nonresponsive acute otitis media were randomized to receive the 1 (n = 83)- or 3 (n = 87)-day intramuscular ceftriaxone regimen (50 mg/kg/day), respectively. Nasopharyngeal cultures for S. pneumoniae were obtained on Days 1, 4 to 5, 11 to 14 and 28 to 30. Susceptibility of S. pneumoniae to penicillin and ceftriaxone was determined by E-test.. On Day 1 nasopharyngeal S. pneumoniae carriage was found in 108 (64%) patients, 54 in each treatment group. Forty-seven of 54 (87%) and 9 of 54 (17%) S. pneumoniae isolates from the one dose group were nonsusceptible to penicillin and ceftriaxone, respectively; the respective values in the three dose group were 49 of 54 (91%) and 8 of 54 (15%). On Days 4 and 5 negative nasopharyngeal cultures were achieved in 43 of 83 (52%) and 70 of 87 (80%) cases from the one dose and three dose group, respectively (P < 0.001). Eradication of penicillin-nonsusceptible S. pneumoniae was achieved on Day 4 to 5 in 18 of 49 (37%) and 39 of 49 (80%) organisms isolated from the one dose and three dose groups, respectively (P < 0.001). Nasopharyngeal S. pneumoniae carriage among evaluable patients on Days 11 to 14 and Days 28 to 30 was 43 of 69 (62%) and 31 of 45 (69%) for the one dose group and 42 of 73 (58%) and 31 of 50 (62%) for the three dose group, respectively (P not significant). A decrease was observed during the study period in the proportion of highly penicillin-resistant S. pneumoniae isolated in the three dose group compared with the one dose group (30, 24, 17 and 13% vs. 30, 27, 19 and 26% at Days 1, 4 to 5, 11 to 14 and 28 to 30, respectively; P = 0.05).. A marked reduction in the carriage of penicillin-nonsusceptible S. pneumoniae (including highly penicillin-resistant organisms) was achieved on Days 4 to 5 of therapy with both ceftriaxone regimens. The 3-day intramuscular ceftriaxone regimen was significantly superior to the 1-day regimen in the reduction of carriage during the treatment period. The reduction of overall S. pneumoniae nasopharyngeal carriage by both ceftriaxone regimens was a short-lived phenomenon followed by rapid recolonization of the nasopharynx.

Topics: Acute Disease; Carrier State; Ceftriaxone; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Bacterial; Female; Follow-Up Studies; Humans; Infant; Injections, Intramuscular; Male; Microbial Sensitivity Tests; Nasopharynx; Otitis Media with Effusion; Pneumococcal Infections; Probability; Prospective Studies; Reference Values; Streptococcus pneumoniae; Treatment Outcome

Over the last decade or so there has been a growing interest in routes of antimicrobial administration other than by the conventional intravenous route for institutionalized patients and for some outpatients. Both oral (PO) and intramuscular (IM) routes of administration are less costly than giving antimicrobial agents by vein (IV). In addition, fewer complications such as catheter-related sepsis and phlebitis are associated with non-IV routes of administration. Furthermore, a reduced-dosage, reduced-volume IM administration of ceftriaxone may provide a tolerable route of administration and equivalent bactericidal activities compared with higher dose IV ceftriaxone. The purpose of this study was to determine the time that the drug concentration remained in excess of the minimum inhibitory concentration (MIC) (T > MIC) and the duration of bactericidal activities of ceftriaxone one gram administered IV, ceftriaxone 250 mg given IM and cefixime 400 mg given orally against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in adult volunteers. Single doses of each agent were administered and serum concentrations were collected over the standard dosing period of 24 h for all study regimens. Ceftriaxone, regardless of route of administration and dose, resulted in bactericidal activities and T > MIC for 100% of the dosing period for S. pneumoniae, H. influenzae, and M. catarrhalis. Cefixime maintained at least 50% T > MIC and bactericidal activity against both isolates each of H. influenzae and M. catarrhalis. Against both isolates of S. pneumoniae, cefixime achieved T > MIC for at least 50% of the dosing period, but did not maintain bactericidal activity. Reduced dose ceftriaxone given IM seems to be a viable alternative to ceftriaxone IV if the pathogen, susceptibility and infection site are known. Based on T > MIC exceeding 50% of the dosing interval, cefixime would be considered an effective alternative to IV therapy against common respiratory tract pathogens. Clinical studies need to be conducted to confirm these findings.

Topics: Administration, Oral; Adult; Blood Bactericidal Activity; Cefixime; Ceftriaxone; Cephalosporins; Community-Acquired Infections; Cross-Over Studies; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Respiratory Tract Infections; Streptococcus pneumoniae

This prospective multicenter study was conducted to define more clearly clinical and laboratory criteria that predict a strong probability of occult bacteremia and to evaluate the effect of empiric broad spectrum antimicrobial treatment of these children. Children 3 to 36 months old with fever > or = 40 degrees C (104 degrees F) or, > or = 39.5 degrees C (103 degrees F) with white blood cells (WBC) > or = 15 x 10(9)/liter, and no focus of infection had blood cultures obtained and were randomized to treatment with oral amoxicillin/potassium clavulanate or intramuscular ceftriaxone. Sixty of 519 (11.6%) study patients had positive blood cultures: Streptococcus pneumoniae, 51; Haemophilus influenzae b, 6; Neisseria meningitidis, 2; and Group B Streptococcus, 1. Subgroups of high risk were identified as fever > or = 39.5 degrees C and WBC > or = 15 x 10(9)/liter, 55 of 331 or 16.6% positive with increasing incidence of positive culture with increasing increments of degrees of leukocytosis to WBC > or = 30 x 10(9)/liter where 9 of 21 or 42.9% were positive. Subgroups of significantly lower risk were identified as fever > or = 39.5 degrees C and WBC < 15 x 10(9)/liter, 5 of 182 or 2.7% positive and those with WBC < 10 x 10(9)/liter, 0 of 99 or 0.0% positive. Children with positive cultures who received ceftriaxone were nearly all afebrile after 24 hours whereas a significant number who received amoxicillin/potassium clavulanate remained febrile. In the 459 culture-negative children more amoxicillin/potassium clavulanate-treated children developed diarrhea and had less improvement in clinical scores after 24 hours than ceftriaxone-treated children.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Child, Preschool; Clavulanic Acids; Drug Therapy, Combination; Female; Fever; Follow-Up Studies; Haemophilus Infections; Humans; Infant; Injections, Intramuscular; Leukocytosis; Male; Meningococcal Infections; Multivariate Analysis; Pneumococcal Infections; Prospective Studies; Regression Analysis; Treatment Outcome

Seventy-seven patients with acute bacterial infections were treated with ceftriaxone (1 gm administered intravenously every 12 hours). The 58 patients evaluable for efficacy had 60 infections, including 39 of the respiratory tract, 14 of the urinary tract, and seven of soft tissue. Five patients were bacteremic. The mean duration of ceftriaxone treatment was eight days for patients with respiratory and urinary tract infections and 13 days for patients with other types of infections. A satisfactory clinical response occurred in 56 (93%) of the infections. Eighty-four (94%) of the 89 pretherapy pathogens were bacteriologically eradicated. Included were all 19 isolates of Haemophilus influenzae, all 15 of Streptococcus pneumoniae, all 12 of Escherichia coli, 22 of the 23 isolates of other Enterobacteriaceae species, three of five isolates of Pseudomonas aeruginosa, and three of four isolates of Staphylococcus aureus. Two cases of superinfection (one with bacteremia) occurred with P aeruginosa. There were two cases each of reinfection and colonization with Streptococcus faecalis. One patient developed manifestations of culture-documented S pneumoniae meningitis eight hours after the first dose was administered. Peak and trough plasma levels of ceftriaxone were 142 and 64 micrograms/ml. Ceftriaxone achieved therapeutic levels in infected cerebrospinal fluid and in the abscess fluid of selected patients. Adverse effects, which were mild, included diarrhea in 4% of the patients and elevated transaminase levels in 10%.

Topics: Adult; Aged; Alanine Transaminase; Bacterial Infections; Cefotaxime; Ceftriaxone; Clinical Trials as Topic; Connective Tissue Diseases; Diarrhea; Escherichia coli Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Middle Aged; Pneumococcal Infections; Respiratory Tract Infections; Sepsis; Streptococcus pneumoniae; Time Factors; Urinary Tract Infections

The safety of ceftriaxone was compared with that of amoxicillin in a randomized study of 91 patients with community-acquired pneumonia. The origin of infection was similar in the two groups. It was proven or probable Streptococcus pneumoniae in 50 percent of the patients and remained uncertain in 40 percent. Ninety percent of the patients who received ceftriaxone were clinically cured compared with 69 percent of those given amoxicillin (p less than 0.05). However, this difference was not apparent among the patients with proven or probable pneumococcal pneumonia. No severe clinical side effects were observed. Cutaneous reactions were more prevalent in the amoxicillin group, whereas mild diarrhea and mucosal candidiasis were more frequent in the ceftriaxone group. Reversible neutropenia was observed in two patients treated with ceftriaxone and none of those treated with amoxicillin.

Topics: Adult; Aged; Amoxicillin; Cefotaxime; Ceftriaxone; Female; Humans; Male; Middle Aged; Neutropenia; Penicillins; Pneumococcal Infections; Pneumonia

Since 2015, 13-valent pneumococcal conjugate vaccine (PCV13) was included in the national immunization program in Taiwan. Subsequently, the serotypes of the main circulating Streptococcus pneumoniae strains have changed. PCV administration is also associated with changes in the antimicrobial susceptibility of S. pneumoniae strains. Therefore, in this study, we analyzed the serotype distribution and antimicrobial susceptibility of S. pneumoniae in pediatric infections.. Children with S. pneumoniae infections, including invasive pneumococcal disease (IPD) and non-IPD, were enrolled from January 2010 to December 2020. The samples were collected from Mackay Memorial Hospital, MacKay Children's Hospital, and Hsinchu Mackay Hospital in Taiwan. We analyzed the epidemiology of sample collection site, infection diagnosis, and the serotype and antimicrobial susceptibility of S. pneumoniae strains. The study period was divided into time points before and after PCV13 administration.. In total, 322 isolates were collected during the study period. The incidence of IPD declined annually, from 29.7% before 2015 to 7.3% after 2015 (p < 0.001). The prevalence of serotype 19 A had increased gradually since 2010 but declined rapidly after 2013. Serotypes 15 A and 23 A were the most common serotypes after 2015. The non-susceptibility of the S. pneumoniae isolates to penicillin, cefotaxime, and ceftriaxone decreased. Based on meningitis breakpoints, the non-susceptibility to cefotaxime and ceftriaxone gradually decreased, but increased in 2020.. PCV13 was considerably effective in reducing the incidence of IPD in children; however, the prevalence of serotypes 15 A and 23 A increased. The increase in antimicrobial non-susceptibility caused by non-vaccine serotypes must be continuously monitored.

Topics: Anti-Infective Agents; Cefotaxime; Ceftriaxone; Child; Hospitals, Pediatric; Humans; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Serotyping; Streptococcus pneumoniae; Taiwan

Serotype 3 has persisted to be an important cause of invasive pneumococcal disease in adults in the post-vaccine era. We aimed to investigate clinical and microbiological characteristics of Streptococcus pneumoniae serotype 3 infection in Taiwan and identify the risk factors associated with severe clinical outcome.. A multicenter observational study was conducted to analyze serotype 3 isolates collected between 2012 and 2021. Demographics, comorbidities, and risk categories were statistically compared with clinical outcome. Antimicrobial susceptibility testing and multilocus sequence typing were performed.. A total of 146 isolates were collected, including 12 isolates regarded as colonizers. Among 134 infected cases, 54 (40.3%) were aged 65 and older. Mortality was significantly associated with diabetes mellitus, immunosuppression, immunodeficiency, high-risk status, and older age. Susceptibility rates were high to levofloxacin (98.9%), moxifloxacin (100%), vancomycin (100%), and ceftriaxone (97.3%). 25.3% (37/146) of the isolates showed intermediate susceptibility and 0.7% (1/146) showed resistance to penicillin. ST180 was the dominant sequence type. ST13 and ST9625 isolates were less susceptible to penicillin and ceftriaxone.. Serotype 3 infection showed a high mortality rate, especially in patients with older ages and comorbidities. Although the incidence rates decreased during the COVID-19 pandemic, serotype 3 remained as an important cause of infection after the implementation of PCV13. Developing a more effective vaccine against serotype 3 and monitoring the antimicrobial-resistant sequence types are necessary.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; COVID-19; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Pandemics; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Risk Factors; Serogroup; Serotyping; Streptococcus pneumoniae

This study aims to analyze the serotype distribution and drug resistance of. Serotypes of. A total of 317 isolates were involved in this study. The most common serotypes were type 19F (34.4%), followed by 19A (15.8%), 23F (11.7%), 6B (11.4%), and 6A(5.0%). The coverage rate of both PCV13 and PCV15 was 83.0%. The coverage of PCV20 was a little higher at 85.2%. The resistance rate against penicillin was 28.6% according to the breakpoints of oral penicillin, which would reach up to 91.8% based on the breakpoints of parenteral penicillin for meningitis. The resistance rates to erythromycin, clindamycin, tetracycline, and sulfamethoxazole-trimethoprim were 95.9%, 90.2%, 88.9%, and 78.8%, respectively. The PCV13 isolate was more resistant to penicillin than the non-PCV13 ones. There was not any significant change found in the serotype distribution since the PCV13 introduction and the COVID-19 control. The resistance rate against oral penicillin slightly elevated to 34.5% in 2018-2019 from 30.7% in 2014-2015 and then decreased significantly to 18.1% in 2020-2021 (. The common serotypes of

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; Child; China; COVID-19; Drug Resistance, Bacterial; Humans; Infant; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Serotyping; Streptococcus pneumoniae

To assess the antimicrobial susceptibility of 14 138 invasive Streptococcus pneumoniae isolates collected in Canada from 2011 to 2020.. Antimicrobial susceptibility testing was performed using the CLSI M07 broth microdilution reference method. MICs were interpreted using 2022 CLSI M100 breakpoints.. In 2020, 90.1% and 98.6% of invasive pneumococci were penicillin-susceptible when MICs were interpreted using CLSI meningitis or oral and non-meningitis breakpoints, respectively; 96.9% (meningitis breakpoint) and 99.5% (non-meningitis breakpoint) of isolates were ceftriaxone-susceptible, and 99.9% were levofloxacin-susceptible. Numerically small, non-temporal, but statistically significant differences (P < 0.05) in the annual percentage of isolates susceptible to four of the 13 agents tested was observed across the 10-year study: chloramphenicol (4.4% difference), trimethoprim-sulfamethoxazole (3.9%), penicillin (non-meningitis breakpoint, 2.7%) and ceftriaxone (meningitis breakpoint, 2.7%; non-meningitis breakpoint, 1.2%). During the same period, annual differences in percent susceptible values for penicillin (meningitis and oral breakpoints) and all other agents did not achieve statistical significance. The percentage of isolates with an MDR phenotype (resistance to ≥3 antimicrobial classes) in 2011 and 2020 (8.5% and 9.4%) was not significantly different (P = 0.109), although there was a significant interim decrease observed between 2011 and 2015 (P < 0.001) followed by a significant increase between 2016 and 2020 (P < 0.001). Statistically significant associations were observed between resistance rates to most antimicrobial agents included in the MDR analysis (penicillin, clarithromycin, clindamycin, doxycycline, trimethoprim/sulfamethoxazole and chloramphenicol) and patient age, specimen source, geographic location in Canada or concurrent resistance to penicillin or clarithromycin, but not biological sex of patients. Given the large isolate collection studied, statistical significance did not necessarily imply clinical or public health significance in some analyses.. Invasive pneumococcal isolates collected in Canada from 2011 to 2020 generally exhibited consistent in vitro susceptibility to commonly tested antimicrobial agents.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Canada; Ceftriaxone; Chloramphenicol; Clarithromycin; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Drug Resistance, Bacterial; Humans; Infant; Paraguay; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae; Vaccines, Conjugate

Following pneumococcal conjugate vaccine (PCV) introduction, community pediatric dispensed prescription rates (DPR) of oral antibiotics declined, in parallel to respiratory tract infection (RTI). We assessed the dynamics of outpatient parenteral ceftriaxone DPR.. Computerized data for children <5 years were examined during 13 years (including 4 pre-PCV years). DPR from clinics with ≥50 insured children, active both before and after PCV implementation were included. Interrupted time series with segmented regression stratified by age and ethnicity, and adjusted for seasonality was applied to show monthly DPR trends.. A total of 29,226 prescriptions were dispensed. No significant trends in ceftriaxone DPR were seen pre-PCV. Shortly after PCV implementation, DPR abruptly and significantly declined, stabilizing in late-PCV period (5 years postimplementation). The dynamics were compared between the two ethnic groups in the region, Jewish and Bedouin children (the latter with higher crowding and respiratory disease rates). Among Jewish children, ceftriaxone was mainly dispensed during winter vs no seasonality among Bedouin children.. In southern Israel, outpatient ceftriaxone DPR declined post-PCV in young children, similar to the trends of RTIs and oral antibiotic prescriptions, suggesting a causative role of PCVs. The differences between the two ethnic groups suggest possible involvement of additional factors.

Topics: Anti-Bacterial Agents; Arabs; Ceftriaxone; Child; Child, Preschool; Humans; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Respiratory Tract Infections; Vaccines, Conjugate

Invasive pneumococcal disease (IPD) is associated with substantial morbidity and mortality in children and elderly populations. Serotype distribution and antibiotic susceptibility of IPD isolates are changing with the implementation of pneumococcal vaccination and increasing antibiotic use worldwide. We aimed to determine serotype distribution, antibiogram, and molecular epidemiology of pneumococci in the late stage of PCV13 era.. Prospective multicenter IPD surveillance study was conducted for adults aged ≥ 19 years from July 2019 to June 2021. Clinical and epidemiologic data were collected. In addition, antibiotic susceptibility test, serotype identification and multi-locus sequence typing (MLST) was taken for pneumococcal isolates.. A total of 160 IPD cases were collected with mean age of 65.1 years (male, 72.5%). Serotyping was taken for 116 available pneumococcal isolates. PCV13 and PPSV23 serotypes were 32.8% (n = 38) and 56.0% (n = 65), respectively. Serotype 3 (13.8%) and 19A (9.5%) were the most common causative agents of IPD, followed by serogroup 11 (6.9%), 23A (6.9%), 10A (4.3%), and 15B (4.3%). Notably, 32.5% of invasive pneumococcal isolates were non-susceptible to ceftriaxone. Serotypes 11A, 11E and 19A pneumococci showed high ceftriaxone non-susceptible rate (80%, 100% and 81.8% respectively), and they were related to sequence type (ST) 166 and ST320. In comparison, most serotype 3 isolates were ceftriaxone susceptible and related to ST180.. PCV serotypes, especially 3 and 19A, are still prevalent in adult IPDs, suggesting that individual PCV13 immunization would be necessary for the elderly people and chronically ill patients. Ceftriaxone non-susceptible rate was remarkably high in invasive pneumococcal isolates.

Topics: Adult; Aged; Ceftriaxone; Child; Humans; Infant; Male; Multilocus Sequence Typing; Pneumococcal Infections; Pneumococcal Vaccines; Prospective Studies; Serogroup; Serotyping; Young Adult

Objectives The multi-center clinical microbiological study in Taiwan aimed to evaluate the impact of childhood PCV13 immunization on pneumococcal disease, and the magnitude of serotype replacement in invasive and non-invasive pneumococcal disease among all age groups. Methods The study of culture-confirmed pneumococcal disease (CCPD) was conducted at four hospitals across Taiwan in 2015-2018. Pneumococcal pneumonia was defined as clinical diagnosis with positive sputum or bronchoalveolar lavage culture. Serotyping, multi-locus sequence typing, and antimicrobial susceptibility testing for penicillin and ceftriaxone were performed. Results A total of 1413 CCPD cases were identified. Invasive pneumococcal disease (IPD) accounted for 13.4% (190/1413) of CCPD. PCV7-type CCPD incidence declined among all age groups between 2015 and 2018. In adults aged 50-64 years, PCV7-type pneumococcal pneumonia incidence in 2018 was 72% lower than that in 2015, and all pneumococcal pneumonia incidence was 35% lower than that in 2015. In children, CCPD incidence was higher in 2018 than in 2015 (IRR 1.75 for age < 5 years, IRR 1.56 for age 5-17 years). Incidence of CCPD caused by non-PCV13-types, mainly 15A and 23A, increased significantly in those younger than 50 years. Serotypes 19A and 19F constituted the largest clonal complex, CC236/320 (n = 280, 19.8%). The rates of penicillin and ceftriaxone non-susceptibility were higher in PCV13-type isolates. Conclusions Childhood PCV13 immunization exerted an indirect protection to vaccine serotype clinically defined non-bacteremic pneumococcal pneumonia among adults, especially those between 50 and 64 years of age. Emerging non-PCV13 serotypes mainly caused non-invasive mucosal disease among children.

Topics: Adolescent; Adult; Anti-Infective Agents; Ceftriaxone; Child; Child, Preschool; Genotype; Humans; Incidence; Middle Aged; Multilocus Sequence Typing; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Serogroup; Serotyping; Streptococcus pneumoniae; Taiwan

Given the significant role of penicillin-nonsusceptible Streptococcus pneumoniae in inducing severe infectious diseases, identifying serotypes and genotypes that can mediate antimicrobial resistance has become a pillar of treatment strategies. This study aims to determine the correlation between the minimum inhibitory concentration of antimicrobial agents and amino acid mutations in penicillin-binding proteins. Moreover, molecular serotyping and multiple-locus variable number tandem repeat analysis typing were first-ever performed to characterize the invasive penicillin-nonsusceptible S. pneumoniae isolates in Iran.. Of 149 isolates, antimicrobial susceptibility tests were performed against penicillin, ceftriaxone, and cefotaxime by the MIC Test Strip, and sequence analysis of the pbp genes was performed through PCR-sequencing method. All penicillin-nonsusceptible S. pneumoniae isolates were serotyped and genotyped by sequential multiplex PCR and multiple-locus variable-number tandem repeat analysis, respectively.. Among pneumococcal isolates, 53 isolates were classified as penicillin-nonsusceptible S. pneumoniae, of which 38 (71.7%) and 15 (28.3%) were resistant and intermediate to penicillin, respectively. Furthermore, ceftriaxone- and cefotaxime-nonsusceptible pneumococci constituted 33 (62.2%) and 29 cases (54.7%), respectively. Of note, there were 8 and 41 different serotypes and multiple-locus variable-number tandem repeat analysis types, respectively.. Due to the increasing resistance to antimicrobial agents, the most efficient approach to preventing pneumococcal infection mortality as vaccine-preventable diseases is focusing on wide-spectrum vaccination. Based on our findings, the 13-valent pneumococcal conjugate vaccine could considerably reduce the incidence of invasive pneumococcal diseases due to the high rate of serotype coverage.

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Microbial Sensitivity Tests; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Serotyping; Streptococcus pneumoniae

In order to characterize pneumococcal endovascular infection in the post-vaccination era, a retrospective nationwide study based on the Israeli Adult IPD database was conducted. Between 2010 and 2019, 0.6% (23 cases) of IPD cases were of endovascular type, occurring mainly in males (72.3%) with underlying medical conditions (78.2%). Additional pneumococcal source (10 patients) and concomitant infections were not uncommon. Penicillin and ceftriaxone susceptibility rates were 65.2% and 91.3%, respectively; 60.9% of the isolates were not covered by the pneumococcal conjugate vaccine. 21.7% of patients died during hospitalization. In conclusion, pneumococcal endovascular infections still carry significant morbidity and mortality.

Topics: Adult; Ceftriaxone; Humans; Infant; Male; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Retrospective Studies; Serotyping; Vaccines, Conjugate

Data related to carriage of Streptococcus pneumoniae (Spn) and antimicrobial resistance patterns in middle-aged and older adults are limited. We assessed the carriage of Spn, and its antibiotic resistance patterns, among participants ≥50 years of age living in the city of Novi Sad during the second year of COVID-19 pandemic.. Analysis of prospectively collected data among participants with or without symptoms of upper respiratory tract infection who visited their elected physicians in the Primary Health Care Centre of Novi Sad (outpatient facility) was conducted from May 18, 2021 to December 7, 2021. Both nasopharyngeal (NP) and oropharyngeal (OP) samples from each participant were collected.. A total of 1042 samples from 521 study subjects (1 NP and 1 OP sample from each person) were collected. Sixteen samples from the same number of persons (3.1%, 95% confidence interval: 1.76%-4.94%) were culture positive for the presence of Spn. Overall, the median age of study participants was 71 years (range, 50-93 years; 90th percentile, 77 years), and most (197/521, 37.8%) of them were 70-79 years of age. A majority of the study subjects were: females (324/521; 62.2%), sampled during May and June 2021 (376/521, 72.2%), those who did not have contact with children aged 0-10 years in the family (403/521; 77.4%), without smokers in the household (443/521; 85.0%), and those who did not receive vaccine against Spn (519/521; 99.6%). Out of 16 Spn positive samples, for six participants, Spn carriage serotypes were obtained and there were four vaccine (6A, 11A, 15B, and 18C) serotypes, and two (6C and 35F) non-vaccine serotypes. Remaining 10 (62.50%) samples were non-typeable isolates of pneumococci. Among four vaccine serotypes, two (6A and 18C) were represented in PCV13, and 18C along with the other two (11A and 15B) in PPSV23 vaccine. The highest level of resistance of Spn isolates was observed for erythromycin, (10 or 62.50%), and tetracycline, (7 or 43.75%), one isolate showed resistance to penicillin, ampicillin, and amoxicillin/amoxicillin-clavulanic acid, while none of them were resistant to ceftriaxone, trimethoprim/sulfamethoxazole and levofloxacin. There were three multi-drug resistant isolates; one was identified as 6C (non-vaccine serotype), and two other were non-typeable isolates of Spn.. In this first study conducted in Serbia on Spn carriage in adults ≥50 years of age, we found low prevalence of Spn carriage and identified 6 serotypes of Spn, four of which were represented in vaccines. These results may support future Spn colonization studies among middle-aged and older adults.

Topics: Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Carrier State; Ceftriaxone; Child; COVID-19; Delivery of Health Care; Erythromycin; Female; Humans; Infant; Levofloxacin; Middle Aged; Nasopharynx; Outpatients; Pandemics; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Serbia; Serogroup; Streptococcus pneumoniae; Tetracyclines; Trimethoprim, Sulfamethoxazole Drug Combination

Streptococcus pneumoniae causes pneumonia and other invasive diseases, and is a leading cause of mortality in the elderly population. The present study aimed to provide current antimicrobial resistance and epidemiological profiles of S. pneumoniae infections in Taiwan.. A total of 252 nonduplicate S. pneumoniae isolates were collected from patients admitted to 16 hospitals in Taiwan between January 2017 and December 2019, and were analyzed. The minimum inhibitory concentration of antibiotics was determined using the Vitek 2 automated system for antimicrobial susceptibility testing. Furthermore, epidemiological profiles of S. pneumoniae infections were analyzed.. Among the strains analyzed, 88% were recognized as invasive pneumococcal strains. According to the Clinical and Laboratory Standards Institute criteria for non-meningitis, the prevalence of penicillin-non-susceptible S. pneumoniae demonstrated a declining trend from 43.6% in 2017 to 17.2% in 2019. However, the rate of penicillin-non-susceptible S. pneumoniae was 85.7% based on the criteria for meningitis. Furthermore, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7% based on the criteria for meningitis. Isolates demonstrated higher susceptibility toward doripenem and ertapenem than toward meropenem and imipenem. An increased rate of non-susceptibility toward levofloxacin was observed in southern Taiwan (15.1%) and elderly patients (≥65 years; 11.4%). Most isolates were susceptible to vancomycin and linezolid.. Empirical treatment with ceftriaxone monotherapy for pneumococcal meningitis should be carefully monitored owing to its high non-susceptibility rate. The susceptibility rates of most isolates to penicillin (used for treating non-meningitis pneumococcal diseases), carbapenems (ertapenem and doripenem), respiratory quinolones (moxifloxacin and levofloxacin), vancomycin, and linezolid suggested the potential of these antibiotics in treating pneumococcal diseases in Taiwan.

Topics: Aged; Anti-Bacterial Agents; Ceftriaxone; Doripenem; Drug Resistance, Bacterial; Ertapenem; Humans; Levofloxacin; Linezolid; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae; Taiwan; Vancomycin

We present a case of a 75-year-old woman with Austrian syndrome: pneumonia, meningitis and endocarditis all due to

Topics: Aged; Agranulocytosis; Anti-Bacterial Agents; Ceftriaxone; Comorbidity; COVID-19; Echocardiography, Transesophageal; Endocarditis, Bacterial; Female; Humans; Meningitis, Bacterial; Pandemics; Pneumococcal Infections; SARS-CoV-2; Streptococcus pneumoniae; Syndrome

Topics: Adenosine Monophosphate; Adult; Aged; Aged, 80 and over; Alanine; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiviral Agents; Azithromycin; Ceftriaxone; Coinfection; COVID-19; COVID-19 Drug Treatment; COVID-19 Testing; Dexamethasone; Female; Humans; Hydroxychloroquine; Male; Middle Aged; Pneumococcal Infections; SARS-CoV-2; Streptococcus pneumoniae

A 42-year-old woman with a history of acute myeloid leukaemia status postallogeneic stem cell transplant presented with fevers, altered mental status, pulmonary infiltrates and septic shock that further progressed to thrombocytopenia and purpura fulminans. Laboratory studies were consistent with a diagnosis of thrombotic thrombocytopenic purpura (TTP). Blood cultures grew

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Diagnosis, Differential; Female; Fibrinolytic Agents; Fingers; Gangrene; Glucocorticoids; Graft vs Host Disease; Humans; Immunologic Factors; Leukemia, Myeloid, Acute; Nose; Plasma Exchange; Pneumococcal Infections; Purpura Fulminans; Purpura, Thrombotic Thrombocytopenic; Rituximab; Shock, Septic; Single-Domain Antibodies; Stem Cell Transplantation; Toes

Streptococcus pneumoniae endophthalmitis is clinically more severe, more difficult to treat, and carry a higher risk of vision loss, evisceration, or enucleation. This study is to investigate the clinical settings, antibiotic susceptibility, and visual outcomes of S. pneumoniae endophthalmitis at a tertiary referral center in Taiwan. S. pneumoniae endophthalmitis was diagnosed in 38 eyes of 38 patients. The main clinical features were postcataract endophthalmitis (n = 13, 34%) and endophthalmitis associated with corneal ulcer (n = 12, 32%), trauma (n = 6, 16%), endogenous etiology (n = 4, 11%), trabeculectomy (n = 2, 5%), and pterygium excision-related scleral ulcer (n = 1, 3%). Presenting visual acuity ranged from counting fingers to no light perception. Pars plana vitrectomy with intravitreal antibiotics was performed in 17 eyes (39%) in primary or secondary treatments. S. pneumoniae isolates were susceptible to vancomycin (38/38, 100%), penicillin (37/38, 97%), ceftriaxone (37/38, 97%), cefuroxime (12/15, 80%), levofloxacin (13/15 ,87%), and moxifloxacin (15/17, 88%). Final visual acuity was better than 20/400 in 3 of 38 eyes (8%), 5/200 to hand motions in 3 eyes (8%), and light perception to no light perception in 32 eyes (84%). Ten eyes (26%) underwent evisceration or enucleation. Although S. pneumoniae isolates were susceptible to vancomycin, S. pneumoniae endophthalmitis had a very poor visual prognosis.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cataract; Cataract Extraction; Ceftriaxone; Cefuroxime; Corneal Ulcer; Endophthalmitis; Eye Enucleation; Eye Injuries; Female; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Moxifloxacin; Penicillins; Pneumococcal Infections; Retrospective Studies; Severity of Illness Index; Streptococcus pneumoniae; Taiwan; Tertiary Care Centers; Trabeculectomy; Treatment Outcome; Vancomycin; Vitrectomy

Antimicrobial-resistant strains of Streptococcus pneumoniae have become one of the greatest challenges to global public health today and inappropriate use of antibiotics and high level of antibiotic use is probably the main factor driving the emergence of resistance worldwide. The aim of this study is, therefore, to assess the antimicrobial resistance profiles and multidrug resistance patterns of S. pneumoniae isolates from patients suspected of pneumococcal infections in Ethiopia.. A hospital-based prospective study was conducted from January 2018 to December 2019 at Addis Ababa city and Amhara National Region State Referral Hospitals. Antimicrobial resistance tests were performed from isolates of S. pneumoniae that were collected from pediatric and adult patients. Samples (cerebrospinal fluid, blood, sputum, eye discharge, ear discharge, and pleural and peritoneal fluids) from all collection sites were initially cultured on 5% sheep blood agar plates and incubated overnight at 37 °C in a 5% CO. Of the 57 isolates, 17.5% were fully resistant to penicillin. The corresponding value for both cefotaxime and ceftriaxone was 1.8%. Resistance rates to erythromycin, clindamycin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole were 59.6%, 17.5%, 38.6%, 17.5 and 24.6%, respectively. Multidrug resistance (MDR) was seen in 33.3% isolates. The most common pattern was co-resistance to penicillin, erythromycin, clindamycin, and tetracycline.. Most S. pneumoniae isolates were susceptible to ceftriaxone and cefotaxime. Penicillin has been used as a drug of choice for treating S. pneumoniae infection. However, antimicrobial resistance including multidrug resistance was observed to several commonly used antibiotics including penicillin. Hence, it is important to periodically monitor the antimicrobial resistance patterns to select empirical treatments for better management of pneumococcal infection.

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Chloramphenicol; Clindamycin; Drug Resistance, Multiple, Bacterial; Erythromycin; Ethiopia; Female; Hospitals; Humans; Male; Microbial Sensitivity Tests; Penicillins; Pneumococcal Infections; Prospective Studies; Streptococcus pneumoniae; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination

The emergence of non-vaccine multidrug-resistant Streptococcus pneumoniae serotypes is on rise. This study was performed to investigate a highly resistant serotype 15A S. pneumoniae isolated from the blood specimen of a 20-month-old patient who died of her infection. The SS40_16 isolate was resistant to erythromycin, co-trimoxazole, tetracycline, and chloramphenicol, as well as to penicillin, ceftriaxone, and cefotaxime (using meningitis cut-off points, Clinical and Laboratory Standards Institute). The isolate belonged to sequence type 1591 (ST1591) and was related to CC81 clonal complex, suggesting the possibility of horizontal gene transfer. Scanning electron microscopy comparison between resistant and sensitive pneumococcal isolates also indicated similar phenotypic characteristics that confer high resistance. The emergence of highly resistant non-vaccine pneumococci is of great concern to public health and in the clinical setting. Pneumococcal surveillance programs represent a crucial tool, not only for determining the impact of pneumococcal conjugate vaccines, but also for monitoring the selective pressure of serotype replacement with regard to the treatment of invasive pneumococcal disease.

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Drug Resistance, Multiple, Bacterial; Erythromycin; Female; Gene Transfer, Horizontal; Humans; Infant; Penicillins; Pneumococcal Infections; Serogroup; Serotyping; Streptococcus pneumoniae

Streptococcus pneumoniae is a major cause of bacterial infection among infants and young children with high morbidity and mortality. The serotype distribution of S. pneumoniae varies with geography, time, age, and disease.. We aimed to investigate the current status of molecular characteristics of S. pneumoniae strains isolated from pediatric patients in Shanghai, China.. Between 2016 and 2018, 73 clinical S. pneumoniae isolates were characterized by capsular serotype, multilocus sequence typing, antibiotic susceptibility, and resistant genes.. The most common serotypes were 19F (39.7%), 19A (16.4%), 6A (11.0%), 14 (9.6%), and 6B (8.2%). The coverage rates of the 7-, 10- and 13-valent pneumococcal conjugate vaccines were 64.4%, 64.4%, and 91.8%, respectively. The five predominant sequence types were ST271 (37.0%), ST320 (19.2%), ST3173 (11.0%), ST876 (6.8%), and ST81 (4.1%), which were mainly associated with serotypes 19F, 19A, 6A, 14, and 23F, respectively. The rates of resistance to penicillin and ceftriaxone were 21.9% and 39.7%, respectively. All strains displayed resistance to macrolides, 54.8% of which possessed both erm(B) and mef(A/E) genes, and 41.1% carried the erm(B) gene alone. Tn2010 (41.1%) was the most common transposon.. Clonal complex 271 (Taiwan19F-14 clone) played a dominant role in the dissemination of pneumococcal isolates. The prevalent serotypes indicated a lack of the 7-valent pneumococcal conjugate vaccine, which has not been included in national immunization programs in mainland China. The high rate of macrolide resistance made the empirical use of macrolides alone not suitable for treating pediatric pneumococcal disease.

Topics: Anti-Bacterial Agents; Ceftriaxone; Child, Preschool; China; Cities; Drug Resistance, Bacterial; Female; Humans; Infant; Macrolides; Male; Microbial Sensitivity Tests; Multilocus Sequence Typing; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae

Invasive pneumococcal disease (IPD) is a major burden causing significant mortality and morbidity. This study was conducted to ascertain the magnitude of the problem of drug resistance, the pneumococcal serotypes that are prevalent in our area, and whether current pneumococcal vaccines are able to cover the prevalent serotypes adequately. A retrospective study was done by reviewing the microbiology registry of our hospital. Details of patients whose blood, cerebrospinal fluid (CSF) or any other sterile fluid grew S. pneumoniae between the period January 1, 2016 and December 31, 2019 were collected. Identification and susceptibility testing were done by Vitek2 as per CLSI 2008 guidelines. Serotyping was attempted for 39 isolates. Fifty-five pneumococcal isolates in blood and CSF were identified over four years from 51 patients, of whom nine belonged to the paediatric age group. Among 55 isolates, 50 were isolated from blood, four had growth of pneumococci in both blood and CSF, and one had growth in CSF alone. Overall non-susceptibility to penicillin was noted in 11 isolates, and 10 isolates were non-susceptible to ceftriaxone. Common serotypes isolated were 9V, 19F, 23F and 6 B. The most common clinical presentation was pneumonia followed by sepsis and meningitis. Five of the 51 patients succumbed to the illness. Penicillin susceptibility among pneumococcal isolates in IPD was 80% and susceptibility to ceftriaxone was 82%. This observation reiterates the view that vancomycin must be added to the empiric therapy of suspected IPD. Most of the identified serotypes are covered by current pneumococcal vaccines, highlighting the pivotal role of pneumococcal vaccine in prevention of IPD.

Topics: Anti-Bacterial Agents; Ceftriaxone; Humans; India; Meningitis; Microbial Sensitivity Tests; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Retrospective Studies; Sepsis; Serogroup; Serotyping; Streptococcus pneumoniae; Vancomycin

To determine the resistance rate of penicillin and ceftriaxone amongst invasive meningitis and nonmeningitis isolates of streptococcus pneumoniae.. The prospective cross-sectional study was conducted from January 2011 to March 2014 at the Clinical Microbiology Laboratory of Aga Khan University, Karachi, and comprised all invasive strains of streptococcus pneumoniae. Penicillin and ceftriaxone susceptibilities were performed and interpreted based on minimum inhibitory concentration breakpoints recommended by Clinical and Laboratory Standards Institute guidelines. Data was analysed using Stata 12.. There were 163 strains isolated from sterile body fluids of 109 patients. Of the total, 46(28%) samples were meningitic while 117(72%) were non-meningitic. Of the meningeal isolates, 12(26%) were resistant to penicillin, while none was resistant to ceftriaxone and vancomycin. None of non meningeal isolates showed resistance to penicillin, ceftriaxone or vancomycin.. There was considerable penicillin resistance among meningeal strains of streptococcus pneumoniae, but here appeared to be no need to add vancomycin for empirical treatment of invasive streptococcus pneumonia infection.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Drug Resistance, Bacterial; Emergency Service, Hospital; Female; Humans; Intensive Care Units; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Middle Aged; Mortality; Pakistan; Penicillins; Pneumococcal Infections; Risk Factors; Sex Factors; Streptococcus pneumoniae; Vancomycin; Young Adult

The phenotypes and genotypes of Streptococcus pneumoniae isolated from invasive pneumococcal diseases (IPDs) were changing all the time. To monitor these changes of phenotypes and genotypes of S. pneumoniae isolates from children, we examined antibiotic susceptibility, serotype distribution and sequence types (STs) of S. pneumoniae, which were isolated before the 13-valent pneumococcal conjugate vaccine (PCV13) introduced into China.. Strains were isolated from children less than 14 years old between January 2013 and May 2017 from Shenzhen Children's Hospital. Serotypes, antibiotic resistance, and genotypes of these isolates were determined using capsular swelling, E-test, and multi-locus sequence typing, respectively.. A total of 94 S. pneumoniae strains were isolated, which belonged to 15 serotypes. The five most prevalent serotypes were 19F (25.5%), 19A (19%), 14 (17%), 23F (7.5%), and 6B (9.6%). We found 42 STs for these isolates. The most abundant STs were ST271 (24.4%), ST876 (17%), and ST320 (10.6%), mainly related to 19F, 14, and 19A, respectively. The potential coverage of PCV13 was 87.2%. Among non-meningitis isolates, the resistance rates to penicillin and ceftriaxone were 0% and 2%. However, the meningitis isolates showed high resistance to penicillin (80%) and ceftriaxone (20%). Most of these isolates (95.7%) were resistant to erythromycin, and 66 (70.2%) strains carried the ermB gene and 24 (25.5%) strains carried both the ermB and mefA/E genes. Serotype 19A showed the highest mean minimum inhibitory concentration (MIC) for penicillin (MIC = 1.486) than the other serotypes, but no significant difference in penicillin MIC among the three main STs (ST271, ST320, and ST876).. The phenotypes and genotypes of invasive pneumococcal isolates from Shenzhen Children's Hospital have changed with the passage of time. Compared with PCV7, PCV13 can more effectively protect Chinese children from IPDs. To some extent, these changes are possibly related to the usage of antibiotics and vaccines.

Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; China; Drug Resistance, Bacterial; Erythromycin; Female; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Infant; Male; Microbial Sensitivity Tests; Multilocus Sequence Typing; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae

Despite the availability of a pneumococcal National Immunization Program, which provides free PPSV23 vaccination for older adults aged ≥65 years in South Korea, pneumococcal pneumonia remains one of the most common respiratory infections, with increasing antimicrobial resistance. From January to December in 2015, all pneumococcal isolates were collected from a 1,050-bed teaching hospital in South Korea. All isolates were analyzed for serotype, genotype, and antimicrobial susceptibility. Demographic, clinical and microbiological data were compared between ceftriaxone susceptible and non-susceptible cases. Among 92 microbiologically identified pneumococcal isolates, ceftriaxone non-susceptible pneumococci (CNSP) accounted for 32 cases (34.8%). Some of these cases also showed levofloxacin resistance (25%, 8/32 isolates) and all CNSP cases were multidrug resistant. Compared to patients with ceftriaxone susceptible pneumococci (CSP), long-term care facility residents (odds ratio [OR] 7.0, 95% confidence interval [CI] 0.8-62.1) and patients with chronic lung (OR 4.1, 95% CI 1.1-15.0) and renal diseases (OR 9.1, 95% CI 1.2-70.5) were more common among those with CNSP on multivariate analysis. PPSV23-unique serotypes not included in PCV13 were more common in CNSP than in CSP (34.4% versus 13.3%, p = 0.02). Regarding genotypes, ST320 (10 cases), ST166 (7 cases) and ST8279 (3 cases) were dominant in CNSP, and ST8279 was only detected in previous long-term care facility residents. Clonal expansion and spread of CNSP strains should be monitored among patients with chronic lung/renal diseases and residents of long-term care facilities.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Assisted Living Facilities; Ceftriaxone; Disease Reservoirs; Drug Resistance, Multiple, Bacterial; Female; Genotype; Humans; Immunization Programs; Male; Microbial Sensitivity Tests; Middle Aged; Pneumococcal Infections; Republic of Korea; Streptococcus pneumoniae; Vaccination

Emergent resistance to antibiotics among Streptococcus pneumoniae isolates is a severe problem worldwide. Antibiotic resistance profiles for S pneumoniae isolates identified from pediatric patients in mainland China remains to be established.The clinical features, antimicrobial resistance, and multidrug resistance patterns of S pneumoniae were retrospectively analyzed at 10 children's hospitals in mainland China in 2016.Among the collected 6132 S pneumoniae isolates, pneumococcal diseases mainly occurred in children younger than 5 years old (85.1%). The resistance rate of S pneumoniae to clindamycin, erythromycin, tetracycline, and trimethoprim/sulfamethoxazole was 95.8%, 95.2%, 93.6%, and 66.7%, respectively. The resistance rates of S pneumoniae to penicillin were 86.9% and 1.4% in non-meningitis and meningitis isolates, while the proportions of ceftriaxone resistance were 8.2% and 18.1%, respectively. Pneumococcal conjugate vaccine was administered to only 4.1% of patients. Penicillin and ceftriaxone resistance, underling diseases, antibiotic resistant risk factors, and poor prognosis appeared more frequently in invasive pneumococcal diseases. The incidence of multidrug resistance (MDR) was 46.1% in patients with invasive pneumococcal disease which was more than in patients with non-invasive pneumococcal disease (18.3%). Patients with invasive pneumococcal disease usually have several MDR coexistence.S pneumoniae isolates showed high resistance to common antibiotics in mainland China. Penicillin and ceftriaxone resistance rate of invasive streptococcal pneumonia patients were significantly higher than that of non-invasive S pneumoniae patients. Alarmingly, 46.1% of invasive clinical isolates were multidrug resistant, so it is important to continued monitor the resistance of S pneumoniae when protein conjugate vaccine (PCV13) is coming in mainland China.

Topics: Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; China; Drug Resistance, Multiple, Bacterial; Erythromycin; Female; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Penicillins; Pneumococcal Infections; Retrospective Studies; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination

To study the clinical characteristics, drug sensitivity of isolated strains, and risk factors of drug resistance in children with invasive pneumococcal disease (IPD).. The clinical characteristics and drug sensitivity of the isolated strains of 246 hospitalized children with IPD in nine grade A tertiary children's hospitals from January 2016 to June 2018 were analyzed.. Of the 246 children with IPD, there were 122 males and 124 females. Their ages ranged from 1 day to 14 years, and among them, 68 (27.6%) patients were less than 1 year old, 54 (22.0%) patients were 1 to 2 years old, 97 (39.4%) patients were 2 to 5 years old, and 27 (11.0%) patients were 5 to 14 years old. Pneumonia with sepsis was the most common infection type (58.5%, 144/246), followed by bloodstream infection without focus (19.9%, 49/246) and meningitis (15.0%, 37/246). Forty-nine (19.9%) patients had underlying diseases, and 160 (65.0%) had various risk factors for drug resistance. The isolated Streptococcus pneumoniae strains were 100% sensitive to vancomycin, linezolid, moxifloxacin, and levofloxacin, 90% sensitive to ertapenem, ofloxacin, and ceftriaxone, but had a low sensitivity to erythromycin (4.2%), clindamycin (7.9%), and tetracycline (6.3%).. IPD is more common in children under 5 years old, especially in those under 2 years old. Some children with IPD have underlying diseases, and most of the patients have various risk factors for drug resistance. Pneumonia with sepsis is the most common infection type. The isolated Streptococcus pneumoniae strains are highly sensitive to vancomycin, linezolid, moxifloxacin, levofloxacin, ertapenem, and ceftriaxone in children with IPD.

Topics: Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Drug Resistance; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae

Invasive pneumococcal disease (IPD) was associated with mortality, but the risk factors associated with mortality remains controversial.. A retrospective cohort study was designed. All patients with IPD from 2011 to 2013 admitted in a medical center were screened and collected for their clinical presentations and laboratory characteristics.. Approximately half of the 134 IPD isolates derived from these patients belonged to three major serotypes (19A, 6A and 3), which are included in 13-valent pneumococcal conjugate vaccine (PCV13), but not in 7-valent pneumococcal conjugate vaccine (PCV7). Ceftriaxone resistance according to non-meningitis criteria was identified in 38% of the IPD isolates, and was the major independent risk factor associated with inappropriate initial therapy that subsequently contributed to mortality of the patients. Infection by serotype 6A, 15B, 19A, 19F, or 23F was the major independent risk factor associated with ceftriaxone resistance (non-meningitis criteria). 77.6% of these isolates belonged to additional PCV13 serotypes, with more than 40% expressing resistance to ceftriaxone. In terms of serotype coverage, PCV13 covered 94.1% of the IPD isolates with ceftriaxone resistance, in comparison to 21.6% only by PCV7.. The increase of ceftriaxone resistance in pneumococci in part driven by PCV7 vaccination in Taiwan is worrisome. The use of PCV13 in children as well as in the elderly population is likely to offer protection from the infection caused by ceftriaxone-resistant pneumococci. It is important to give an effective drug such as penicillin, fluoroquinolones or vancomycin in 2 days for improving outcome of IPD patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; Ceftriaxone; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Pneumococcal Infections; Retrospective Studies; Risk Factors; Serogroup; Streptococcus pneumoniae; Survival Analysis; Taiwan; Young Adult

Acute otitis media (AOM) nonresponsive to antibiotics is most commonly caused by antibiotic-resistant Streptococcus pneumoniae and Haemophilus influenzae. A strategy for treating these infections with parenteral ceftriaxone was adopted at the Children's Hospital Iceland. The 10-valent pneumococcal H. influenzae protein D-conjugate vaccine was introduced into the vaccination program in Iceland in 2011. The aim was to study its effect on the incidence of AOM with treatment failure.. This retrospective observational study included children who visited the Children's Hospital Iceland because of AOM or received ceftriaxone, regardless of indication from 2008-2015. Incidence rate was calculated for prevaccine (2008-2011) and postvaccine (2012-2015) periods using person-years at risk within the hospital's referral region. Incidence rate ratio of ceftriaxone treatment episodes of AOM was calculated using the Mantel-Haenzel method adjusting for age. Incidence risk ratio of ceftriaxone treatment if presenting to the hospital with AOM was calculated to adjust for rate of AOM visits.. Visits for AOM decreased from 47.5 to 33.9 visits per 1000 person-years, incidence rate ratio (IRR) 0.86 (95% confidence interval [CI]: 0.81-0.91), P < 0.001. Fewer AOM episodes were treated with ceftriaxone, decreasing from 6.49 to 2.96 treatment episodes per 1000 person-years, with an overall Mantel-Haenzel adjusted IRR 0.45 (95% CI: 0.37-0.54; P < 0.001). This remained significant after adjusting for the decrease in AOM visits, IRR 0.53 (95% CI: 0.44-0.63; P < 0.001).. Visits for AOM and ceftriaxone use decreased significantly after H. influenzae protein D-conjugate vaccine introduction. The observed decrease in ceftriaxone use is presumed to represent a decline in AOM with treatment failure, secondary to a decrease in resistant infections.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Proteins; Carrier Proteins; Ceftriaxone; Child; Child, Preschool; Haemophilus Infections; Haemophilus Vaccines; Humans; Iceland; Immunoglobulin D; Incidence; Infant; Infant, Newborn; Lipoproteins; Otitis Media; Pneumococcal Infections; Pneumococcal Vaccines; Retrospective Studies; Treatment Failure

Iatrogenic cerebrospinal fluid (CSF) rhinorrhea in a bilateral frontal decompressive craniectomy patient triggered by strenuous sport is rare. To the best of our knowledge, no similar case has yet been reported.. Herein, we report a case of CSF rhinorrhea in a 37-year-old man. He had previously suffered a traumatic brain injury in a traffic accident, and a subsequent bilateral frontal decompressive craniectomy operation was performed. Based on the frontal skull defect peculiarity, strenuous exercise may have caused drastic CSF pressure waves to tear the dura mater of the anterior skull base, resulting in CSF rhinorrhea.. The thin-slice computerized tomography (CT) images revealed a frontal skull defect and the open frontal sinus. In addition, in the opened frontal sinus, low-density liquid-filled areas were visible.. During surgery, the torn dura was carefully repaired, and the frontal sinus was filled with temporal muscle, fascia, and fibrin glue. A simultaneous cranioplasty was performed.. The patient was followed-up postoperatively for 12 months to date without rhinorrhea recurrence. Recovery was uneventful.. Patients with skull defects should avoid strenuous sports, and cranioplasty should be performed as early as possible in order to decrease the likelihood of a dural tear and prevent the occurrence of CSF leakage. After cranioplasty, the skull should be restored to a closed state to reduce the damaging effects of CSF waves during movement. It is important to maintain normal intracranial pressure to reduce the recurrence rate of CSF rhinorrhea.

Topics: Accidents, Traffic; Adult; Anti-Bacterial Agents; Brain Injuries, Traumatic; Ceftriaxone; Cerebrospinal Fluid Rhinorrhea; Decompressive Craniectomy; Dura Mater; Exercise; Frontal Sinus; Humans; Male; Meningitis, Bacterial; Pneumococcal Infections; Postoperative Complications; Skull Base

Topics: Ceftriaxone; Debridement; Fasciitis, Necrotizing; Fasciotomy; Fosfomycin; Humans; Immunocompromised Host; Male; Middle Aged; Penicillin Resistance; Pneumococcal Infections; Salvage Therapy; Streptococcus pneumoniae; Treatment Outcome

We report the case of a 17-year-old adolescent girl with systemic lupus erythematosus with disseminated pneumococcal infection leading to purulent pericarditis with cardiac tamponade. Although pericarditis is not an uncommon entity in autoimmune diseases such as systemic lupus erythematosus, purulent pericarditis is a rare cause (<1%) of this presentation.

Topics: Acute Pain; Administration, Intravenous; Adolescent; Anti-Bacterial Agents; Cardiac Tamponade; Ceftriaxone; Chest Pain; Echocardiography; Electrocardiography; Female; Humans; Lupus Erythematosus, Systemic; Pericardiocentesis; Pericarditis; Pneumococcal Infections; Streptococcus pneumoniae; Tomography, X-Ray Computed; Treatment Outcome

A previously healthy man presented with fever for 2 days and rapidly progressive purpuric rash for 1 day. He progressed into hypotension, disseminated intravascular coagulation and refractory shock despite resuscitation and early antibiotic commencement. Blood culture grew

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Disseminated Intravascular Coagulation; Fatal Outcome; Gram-Positive Bacteria; Humans; Hypotension; Male; Pneumococcal Infections; Purpura Fulminans; Resuscitation; Shock, Septic; Streptococcus pneumoniae; Time Factors

Pediatric recipients of hematopoietic stem cell and solid organ transplants are at increased risk of invasive pneumococcal infections (IPI). Data on IPI in this population are scarce. To our knowledge, this is the first study describing the epidemiology of IPI among pediatric transplant recipients in the pneumococcal conjugate vaccine (PCV) era.. We identified transplant recipients with IPI at 8 children's hospitals in the U.S. from our surveillance database (2000-2014). Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. Categorical variables were analyzed by Fisher's exact test and continuous variables with nonparametric tests. Indirect cohort study design was used to calculate vaccine effectiveness.. We identified 65 episodes of IPI in transplant recipients. Recurrent IPI was observed in 10% of transplant recipients. The IPI crude incidence rate in solid organ transplant recipients was higher than in the general population. Most IPI episodes occurred >6 months after transplantation. Bacteremia and pneumonia were the most common presentations. Meningitis was unusual. No case fatalities were observed. Serotype 19A was the most common serotype (n=10), followed by 6C (n=7). In 2010-2014, 37% of IPI was caused by PCV13 serotypes. Four cases of vaccine breakthrough were identified. Most isolates were susceptible to penicillin and ceftriaxone. Pneumococcal conjugate and polysaccharide immunization rates were low.. Pediatric transplant recipients remain at increased risk of IPI in the vaccine era. Most cases presented as a late post-transplant infection. The interval between transplantation and IPI may allow adequate time for pneumococcal immunization.

Topics: Adolescent; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Child; Child, Preschool; Cohort Studies; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunization Schedule; Immunocompromised Host; Incidence; Infant; Male; Microbial Sensitivity Tests; Organ Transplantation; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Prospective Studies; Recurrence; Serotyping; Streptococcus pneumoniae; Vaccines, Conjugate

Streptococcus pneumoniae is a common cause of sepsis. Effective complement activation is an important component of host defence against invading pathogens, whilst excessive complement activation has been associated with endothelial dysfunction and organ damage. The alternative pathway amplification loop is important for the enhancement of complement activation. Factor H is a key negative regulator of the alternative pathway amplification loop and contributes to tight control of complement activation. We assessed the effect of inhibition of the alternative pathway on sepsis associated inflammation and disease severity using human factor H treatment in a clinically relevant mice model of pneumococcal sepsis. Mice were infected intravenously with live Streptococcus pneumoniae. At the first clinical signs of infection, 17 hours post-infection, mice were treated with ceftriaxone antibiotic. At the same time purified human factor H or in controls PBS was administered. Treatment with human factor H did not attenuate disease scores, serum pro-inflammatory cytokines, or vascular permeability and did not significantly affect C3 and C3a production at 26 h post-infection. Therefore, we conclude that inhibition of the alternative complement pathway by exogenous human factor H fails to attenuate inflammation and vascular leakage at a clinically relevant intervention time point in pneumococcal sepsis in mice.

Topics: Animals; Anti-Bacterial Agents; Capillary Permeability; Ceftriaxone; Complement Factor H; Cytokines; Disease Models, Animal; Female; Humans; Mice; Mice, Inbred C57BL; Pneumococcal Infections; Sepsis; Streptococcus pneumoniae

Topics: Anti-Bacterial Agents; Catheterization, Peripheral; Ceftriaxone; Drainage; Epidural Abscess; Humans; Laminectomy; Magnetic Resonance Imaging; Male; Middle Aged; Neck; Pneumococcal Infections; Spinal Cord Compression; Streptococcus pneumoniae; Tomography, X-Ray Computed

In Republic of Korea, a 7-valent pneumococcal conjugated vaccine (PCV7) was licensed for use in infants in 2003, and 13-valent PCV (PCV13) replaced it since 2010. We investigated trends in serotype distribution and antibiotic susceptibility of pneumococcal isolates from adult patients with invasive pneumococcal diseases (IPD). Invasive pneumococcal isolates from adult patients of ≥ 16 years of age were collected from 1997 to 2012. Serotypes of the isolates were determined by the Quellung reaction. Distribution of serotypes was analyzed according to the vaccine types. Antibiotic susceptibility was tested by using E-test strips. A total of 272 invasive pneumococcal isolates were included. The most common serotypes were serotype 19F (8.5%, 23/272), and serotype 3 (8.1%, 22/272), and 24.6% (67/272) of the isolates were of non-vaccine serotypes. Of the 272 isolates, 2.6% (7/272) were penicillin MICs of ≥ 4 µg/mL. The proportion of the PCV13 serotypes decreased from 63.3% (50/79) in 1997-2003 to 48.6% (17/35) in 2011-2012, whereas that of non-vaccine serotypes was 26.6% (21/79) and 25.7% (9/35), respectively, for the same periods. The proportion of the PCV13 serotypes showed a decreasing trend among adult patients with IPD over the study period.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Ceftriaxone; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Penicillins; Pneumococcal Infections; Republic of Korea; Serogroup; Serotyping; Streptococcus pneumoniae; Young Adult

The prevalence of Serotype 6D Streptococcus pneumoniae was reported relatively high in South Korea. Since the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), serotype replacement was observed. This study was designed to better clarify genetic diversity of pneumococcal serotype 6D and its clinical characteristics after introduction of PCV7 in 2000.. We performed serotyping analysis with 1298 pneumococcal isolates from clinical specimens in South Korea from 2004 to 2011. Multilocus sequence typing was performed, and minimal inhibitory concentration was determined for the available serotype 6D and nontypeable (NT) pneumococcal isolates during the 2006-2007 period.. The proportion of serotype 6D pneumococci increased from 0.8% (2004-2007) to 2.9% (2008-2011) of all clinical pneumococcal isolates, accounting for 14.9% of serogroup 6 pneumococci in South Korea. NT pneumococci markedly increased to 13.3% during 2006-2007 in advance of the increase in serotype 6D. Among the 26 available serotype 6D pneumococcal isolates, ST282 was predominant (23 isolates, 88.5%). The STs of NT pneumococci (26 isolates) were diverse, but clonal complex 271 was the dominant clone. The oral penicillin non-susceptibility rate was 92.3% (24 among 26 isolates) for both serotype 6D and NT pneumococci. The ceftriaxone non-susceptibility rates of serotype 6D and NT pneumococci were 7.7% and 3.8%, respectively.. ST228(6D) strain expanded, particularly among old adults with comorbidities in South Korea. Both antibiotic and PCV7 pressure might have contributed to the selective increase of NT and serotype 6D pneumococci.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Female; Genetic Variation; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Pneumococcal Infections; Pneumococcal Vaccines; Republic of Korea; Serogroup; Serotyping; Streptococcus pneumoniae; Vaccines, Conjugate; Young Adult

S. pneumoniae is the leading cause of acute bacterial meningitis (ABM) in children. Vaccination using the 10-valent conjugate vaccine (PCV-10) was recently introduced into the National Immunization Program in Mozambique, but data on serotype coverage of this vaccine formulation are scarce. In this study, we investigated the serotype distribution and antimicrobial resistance of isolates of S. pneumoniae causing ABM in children < 5 years at the two largest hospitals in Mozambique.. Between March 2013 and March 2014, a total of 352 cerebrospinal fluid (CSF) samples were collected from eligible children, of which 119 (33.8 %) were positive for S. pneumoniae. Of these, only 50 samples met the criteria for serotyping and were subsequently serotyped using sequential multiplex PCR (SM-PCR), but 15 samples were non-typable.. The most common serotypes of S. pneumoniae were 1 (18.2 %), 5 (15.2 %), 14 (12.1 %), 9 V (12.1 %), 23 F (9.1 %), 6A (9.1 %), 4 (9.1 %) and 6B (6.1 %). Serotypes 1, 5, 9 V, 6A and 12 were mostly prevalent in Northern Mozambique, while serotypes 23 F, 4, 6B, 3 and 15B were predominant in Southern. Serotype coverage of PCV-10 and PCV-13 vaccine formulations were 81.8 % and 93.9 %, respectively. Serotypes 1, 3, 4, 6B, 14, 23 F were resistant to penicillin and sensitive to ceftriaxone.. Our findings shows that changing the current in use PCV-10 vaccine formulation to PCV-13 formulation might increase substantially the protection against invasive strains of S. pneumoniae as the PCV-10 vaccine formulation does not cover the serotypes 3 and 6A, which are prevalent in Mozambique.

Topics: Anti-Bacterial Agents; Ceftriaxone; Child, Preschool; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Epidemiological Monitoring; Female; Humans; Immunization Programs; Infant; Infant, Newborn; Male; Meningitis, Bacterial; Microbial Sensitivity Tests; Mozambique; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Polymerase Chain Reaction; Prevalence; Serotyping; Streptococcus pneumoniae

Although the majority of pneumococcal infections occur in the developing world, pneumococcal epidemiology is poorly understood in these settings. The aim of the study was to investigate the epidemiology of pneumococcal carriage among children younger than 5 years at a paediatric healthcare centre in Ghana.. Four-hundred and twenty-three children were randomly sampled and nasopharyngeal specimens were collected from them. The specimens were cultured for Streptococcus pneumoniae, and the isolates were subjected to antibiotic susceptibility testing and serotyping by latex agglutination. Epidemiological data on demographic and clinical features of the study subjects were collected.. The prevalence of pneumococcal carriage was 48.9% (207/422), with age groups 43-48 months having the highest carriage prevalence. In the multivariate analysis, pneumococcal carriage was significantly associated with runny nose (odds ratio = 1.9, p = 0.003) and day-care attendance (odds ratio = 1.5, p = 0.04). No pneumococcal resistance was observed for ceftriaxone, while the prevalence of resistance to the other antibiotics tested was: cotrimoxazole 100%, ampicillin 88%, tetracycline 78%, penicillin 63% and erythromycin 24%. Fourteen different pneumococcal serogroups/serotypes were identified and serogroup 6 was the most prevalent (30%), followed by serotype 19 (20%).. We conclude that pneumococcal carriage among the study children is high and the carried strains have a high level of resistance (> 50%) to several antibiotics. Ceftriaxone is a suitable antibiotic for treating pneumococcal infections in Ghana, and the use of this antibiotic coupled with the pneumococcal vaccination is expected to significantly reduce the burden of pneumococcal disease in the country.

Topics: Anti-Bacterial Agents; Carrier State; Ceftriaxone; Child, Preschool; Drug Resistance, Bacterial; Erythromycin; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Nasopharynx; Penicillins; Pneumococcal Infections; Prevalence; Serogroup; Streptococcus pneumoniae

Topics: Adult; Anti-Bacterial Agents; Brain Edema; Ceftriaxone; Humans; Magnetic Resonance Imaging; Male; Meningitis, Pneumococcal; Otitis Media; Pneumococcal Infections

Preference for combination therapy to treat infection due to multidrug-resistant S. pneumoniae (MDRSP) has not been well elucidated in previous studies.. In the present study, 19 antibiotics in combinations were tested against an MDRSP isolate. In vitro susceptibility studies including minimum inhibitory concentration (MIC), minimal bactericidal concentrations (MBC) and disk agar diffusion (DAD), tolerance to resistant antibiotics, checkerboard assay, time-kill curve, hemolytic assay, and autolysis assay were performed on the test strain to study its in vitro susceptibility to combination therapy.. From the checkerboard assay and time-kill curve, it was observed that a combination of levofloxacin (MIC, 16 µg/mL) and ceftriaxone (MIC, 2 µg/mL), at sub-MIC concentration was synergistic and most effective against the MDRSP isolate (penicillin MIC, > 64 µg/mL). Hemolytic activities also increased significantly with combination therapy compared to monotherapy (p < 0.05). Moreover, the hemolytic activity of levofloxacin in combination with ceftriaxone was better than ciprofloxacin plus ceftriaxone or cefepime. The autolysis rate was also found to increase rapidly within one hour of exposure to levofloxacin plus ceftriaxone, and this was found to be significantly different from the other combinations at the fifth and sixth hour post incubation (p < 0.05).. This data suggests that this combination is bactericidal in vitro, and requires further studies in in vivo models for treatment against MDRSP infections.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Ceftriaxone; Drug Synergism; Drug Tolerance; Humans; Levofloxacin; Microbial Sensitivity Tests; Microbial Viability; Pneumococcal Infections; Streptococcus pneumoniae

Topics: Anti-Bacterial Agents; Ceftriaxone; Drug Synergism; Humans; Levofloxacin; Microbial Sensitivity Tests; Penicillins; Pneumococcal Infections; Serogroup; Streptococcus pneumoniae

The aim of this study was to determine serotype distribution and investigate antimicrobial resistance patterns of Streptococcus pneumoniae in healthy Turkish children in the era of community-wide pneumococcal conjugate vaccine (PCV7). The study was conducted on 1,101 healthy children less than 18 years of age. Specimens were collected with nasopharyngeal swabs between April 2011 and June 2011. Penicillin and ceftriaxone susceptibilities were determined by E-test according to the 2008 Clinical Laboratory Standards Institute, and serotypes of the isolates were determined by Quellung reaction. The nasopharyngeal pneumococcal carriage rate was 21.9 % (241/1,101). Using the meningitis criteria of minimum inhibitory concentration values, 73 % of the isolates were resistant to penicillin and 47.7 % of them were resistant to ceftriaxone. Half of all pneumococcal isolates were serotyped as 19F (15.2 %), 6A (15.2 %), 23F (10.3 %), and 6B (9.3 %) and surprisingly, no serotype 19A was isolated. Serotype coverage rates of PCV7 and non-PCV7 were 46.2 and 53.8 %, respectively. The most common penicillin- and ceftriaxone-resistant serotypes were 6A, 6B, 14, 19F, and 23F. Penicillin- and ceftriaxone-resistant isolates were more prevalent in serotypes covered by PCV7 than the non-PCV7 serotypes.. After the community-wide PCV7 vaccination, more non-PCV7 serotypes were isolated from the carriers compared to the time before PCV7 was used especially the serotype 6A, and the antimicrobial resistance of pneumococci was significantly increased.

Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Drug Resistance, Bacterial; Female; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Immunization Schedule; Infant; Male; Nasopharynx; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Serotyping; Streptococcus pneumoniae; Turkey

Endotoxin tolerance improves outcomes from gram negative sepsis but the underlying mechanism is not known. We determined if endotoxin tolerance before or after pneumococcal sepsis improved survival and the role of lymphocytes in this protection.. Mice received lipopolysaccharide (LPS) or vehicle before or after a lethal dose of Streptococcus pneumoniae. Survival, quantitative bacteriology, liver function, and cytokine concentrations were measured. We confirmed the necessity of Toll-like receptor 4 (TLR4) for endotoxin tolerance using C3H/HeN (TLR4 replete) and C3H/HeJ (TLR4 deficient) mice. The role of complement was investigated through A/J mice deficient in C5 complement. CBA/CaHN-Btk(xid/)/J mice with dysfunctional B cells and Rag-1 knockout (KO) mice deficient in T and B cells delineated the role of lymphocytes.. Endotoxin tolerance improved survival from pneumococcal sepsis in mice with TLR4 that received LPS pretreatment or posttreatment. Survival was associated with reduced bacterial burden and serum cytokine concentrations. Death was associated with abnormal liver function and blood glucose concentrations. Endotoxin tolerance improved survival in A/J and CBA/CaHN-Btk(xid/)/J mice but not Rag-1 KO mice.. TLR4 stimulation before or after S. pneumoniae infection improved survival and was dependent on T-cells but did not require an intact complement cascade or functional B cells.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Blood Glucose; Ceftriaxone; Cytokines; Female; Immune Tolerance; Immunity, Innate; Injections, Intravenous; Lipopolysaccharides; Lung; Mice; Mice, Knockout; Pneumococcal Infections; Sepsis; Streptococcus pneumoniae; Survival Analysis; T-Lymphocytes; Toll-Like Receptor 4

It is important to monitor β-lactam antimicrobial nonsusceptibility trends for Streptococcus pneumoniae to inform empirical treatment guidelines. In this study, we describe penicillin and ceftriaxone susceptibility trends using national laboratory-based pneumococcal surveillance data from 2003 to 2010. A sentinel enhanced-site patient subset (2009 to 2010) contributed to the risk factor and mortality analyses. We included 9,218 invasive pneumococcal disease (IPD) cases for trend analyses and 2,854 IPD cases for risk factor and mortality analyses. Overall, we detected no significant changes in penicillin (patients <5 years of age, P = 0.50; patients ≥ 5 years of age, P = 0.05) or ceftriaxone nonsusceptibility rates (patients <5 years of age, P = 0.21; patients ≥ 5 years of age, P = 0.60). Factors associated with ceftriaxone nonsusceptibility on multivariate analysis were an age of <5 years (<1 year of age: adjusted odds ratio [aOR], 2.87; 95% confidence interval [CI], 1.70 to 4.86; 1 to 4 years of age: aOR, 2.58; 95% CI, 1.53 to 4.35, versus 25 to 44 years of age), province (Gauteng [aOR, 2.46; 95% CI, 1.26 to 4.84], and Northern Cape [aOR, 4.52; 95% CI, 1.95 to 10.52] versus KwaZulu-Natal), β-lactam use within 24 h preceding admission (aOR, 2.52; 95% CI, 1.41 to 4.53), and 13-valent vaccine serotypes (aOR, 51.64; 95% CI, 7.18 to 371.71). Among patients ≥ 5 years of age with meningitis who were treated according to current guidelines, HIV-infected patients (aOR, 2.94; 95% CI, 1.32 to 6.54) and patients infected with ceftriaxone-nonsusceptible isolates (aOR, 3.17; 95% CI, 1.27 to 7.89) had increased mortality rates. Among children <5 years of age with meningitis, mortality was increased in HIV-infected patients (aOR, 3.04; 95% CI, 1.40 to 6.56) but not in those with ceftriaxone-nonsusceptible isolates. Penicillin and ceftriaxone nonsusceptibility remained stable over the study period. Ceftriaxone nonsusceptibility was associated with increased mortality among patients ≥5 years of age with meningitis. The introduction of a pneumococcal conjugate vaccine may reduce ceftriaxone-nonsusceptible meningitis.

Topics: Adolescent; Adult; Age Factors; Aged; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Drug Resistance, Bacterial; Female; Humans; Infant; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Middle Aged; Penicillins; Pneumococcal Infections; Public Health Surveillance; Risk Factors; South Africa; Streptococcus pneumoniae; Young Adult

Totals of 8.7% (103/1,190) and 21.0% (249/1,190) of the Streptococcus pneumoniae isolates recovered from specimens collected in the United States during the 2011-2012 AWARE (Assessing Worldwide Antimicrobial Resistance Evaluation) Surveillance Program were ceftriaxone nonsusceptible according to the CLSI (≤ 1 μg/ml for susceptible) and EUCAST (≤ 0.5 μg/ml for susceptible) criteria, respectively. Decreased susceptibility to ceftriaxone (MIC, 1 μg/ml) was frequently observed among serotypes 19 A (51.4%; 128/249) and 35 B (29.7%; 74/249), which were most often observed in the East South Central and South Atlantic U.S. Census regions. Ceftaroline (MIC50/90, 0.12/0.25 μg/ml) remained active (≥ 96.8% susceptible) when tested against these less susceptible isolates.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Ceftaroline; Ceftriaxone; Cephalosporins; Humans; Microbial Sensitivity Tests; Molecular Epidemiology; Pneumococcal Infections; Serogroup; Serotyping; Streptococcus pneumoniae; United States

In this study, our objective was to determine whether a synergistic antimicrobial combination in vitro would be beneficial in the downregulation of pneumococcal virulence genes and whether the associated inflammation of the lung tissue induced by multidrug-resistant Streptococcus pneumoniae infection in vivo needs to be elucidated in order to consider this mode of therapy in case of severe pneumococcal infection. We investigated in vivo changes in the expression of these virulence determinants using an efficacious combination determined in previous studies. BALB/c mice were infected with 10(6) CFU of bacteria. Intravenous levofloxacin at 150 mg/kg and/or ceftriaxone at 50 mg/kg were initiated 18 h postinfection; the animals were sacrificed 0 to 24 h after the initiation of treatment. The levels of cytokines, chemokines, and C-reactive protein (CRP) in the serum and lungs, along with the levels of myeloperoxidase and nitric oxide the inflammatory cell count in bronchoalveolar lavage fluid (BALF), changes in pneumolysin and autolysin gene expression and COX-2 and inducible nitric oxide synthase (iNOS) protein expression in the lungs were estimated. Combination therapy downregulated inflammation and promoted bacterial clearance. Pneumolysin and autolysin expression was downregulated, with a concomitant decrease in the expression of COX-2 and iNOS in lung tissue. Thus, the combination of levofloxacin and ceftriaxone can be considered for therapeutic use even in cases of pneumonia caused by drug-resistant isolates.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; Bronchoalveolar Lavage Fluid; Ceftriaxone; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Levofloxacin; Male; Mice; Mice, Inbred BALB C; N-Acetylmuramoyl-L-alanine Amidase; Pneumococcal Infections; Pneumonia; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Streptolysins; Virulence; Virulence Factors

Topics: Aged; Anti-Bacterial Agents; Bile; Ceftriaxone; Chemical Precipitation; Cholecystitis; Diabetes Mellitus; Humans; Male; Pneumococcal Infections

The resistance of gram-negative bacilli is one of the most important areas in modern medicine, however it hasn't been highlighted the role of the third generation cephalosporins and in particularly ceftriaxone in the selection of gram-negative bacilli resistant to these agents. Paradoxically, ceftriaxone, like the rest of the molecules of this generation, whose initial indication were gram- negative infections began to be used as an agent of choice in pneumococcal infections. The broad spectrum activity of this molecule with its favorable pharmacokinetic properties replaces other agents by this antibiotic in the treatment of a wide range of community acquired infections. However, it wasn't considered the action of this cephalosporin on the microbiome, particularly the intestinal flora, which allowed the selection of enterobacteria that by genetic events, especially parental β-lactamases mutations (TEM-1, TEM-2, SHV-1), developed resistance to third-generation cephalosporins. The decreased susceptibility to penicillin in Streptococcus pneumoniae isolates that stimulated the growing use of ceftriaxone, was one of the main drivers for the development of resistance to third-generation cephalosporins in gram-negative bacilli.

Topics: Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Humans; Pneumococcal Infections; Streptococcus pneumoniae

Acute perturbations in the hemostatic balance of anticoagulation and procoagulation antecede the manifestation of purpura fulminans, a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin. Hallmarks include small vessel thrombosis, tissue necrosis and disseminated intravascular thrombosis. The course may be rapidly fulminant resulting in multiorgan failure with thrombotic occlusion of the vasculature, leading to distal extremity ischemia and necrosis. Depletion of protein C (PC) has been emphasized in the pathogenesis. Early intravenous antibiotic administration and hemodynamic support are cornerstones in management. Herein, we report a case of pneumococcal sepsis-induced purpura fulminans limited to the skin in an asplenic adult patient without the development disseminated intravascular coagulation.

Topics: Administration, Intravenous; Amputation, Surgical; Anti-Bacterial Agents; Ceftriaxone; Debridement; Female; Fingers; Hand; Humans; Leg; Middle Aged; Pneumococcal Infections; Purpura Fulminans; Purpura, Thrombocytopenic, Idiopathic; Sepsis; Skin Transplantation; Splenectomy; Streptococcus pneumoniae; Treatment Outcome

To investigate the impact of penicillin nonsusceptibility on clinical outcomes of patients with nonmeningeal Streptococcus pneumoniae bacteremia (SPB), a retrospective cohort study was performed. The characteristics of 39 patients with penicillin-nonsusceptible SPB (PNSPB) were compared to those of a group of age- and sex-matched patients (n = 78) with penicillin-susceptible SPB (PSSPB). Susceptibility to penicillin was redetermined by using the revised Clinical and Laboratory Standards Institute (CLSI) penicillin breakpoints in CLSI document M100-S18. Although the PNSPB group tended to have more serious initial manifestations than the PSSPB group, the two groups did not differ significantly in terms of their 30-day mortality rates (30.8% versus 23.1%; P = 0.37) or the duration of hospital stay (median number of days, 14 versus 12; P = 0.89). Broad-spectrum antimicrobial agents, such as extended-spectrum cephalosporins, vancomycin, and carbapenem, were frequently used in both the PNSPB and PSSPB groups. Multivariate analysis revealed that ceftriaxone nonsusceptibility (adjusted odds ratio [aOR] = 4.88; 95% confidence interval [CI] = 1.07 to 22.27; P = 0.041) was one of the independent risk factors for 30-day mortality. Thus, when the 2008 CLSI penicillin breakpoints are applied and the current clinical practice of using wide-spectrum empirical antimicrobial agents is pursued, fatal outcomes in patients with nonmeningeal SPB that can be attributed to penicillin nonsusceptibility are likely to be rare. Further studies that examine the clinical impact of ceftriaxone nonsusceptibility in nonmningeal SPB may be warranted.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Ceftriaxone; Child; Child, Preschool; Female; Humans; Infant; Length of Stay; Male; Middle Aged; Penicillin Resistance; Penicillins; Pneumococcal Infections; Retrospective Studies; Streptococcus pneumoniae; Survival Rate; Treatment Outcome; Vancomycin

Acute otitis media is the most common respiratory tract infection in infancy and early childhood that is managed with antimicrobial agents. Ninety-three per cent of the cases diagnosed in Spain are treated with antibiotics, and Streptococcus pneumoniae and untypeable Haemophilus influenzae are the most frequently isolated pathogens. The aim of this work was to evaluate the usefulness of amoxicillin, amoxicillin/clavulanate and ceftriaxone for the empirical treatment of acute otitis media, looking at the pharmacokinetic variability and the antimicrobial susceptibility of paediatric strains of the two main pathogens responsible for AOM in Spain, Streptococcus pneumoniae and Haemophilus influenzae.. Free-drug plasma concentrations were simulated and the probability of target attainment at each minimum inhibitory concentration and the cumulative fraction of response (CFR) were determined. Microbiological susceptibility information was extracted from SAUCE 3 surveillance.. CFR with amoxicillin varied from 83% to 96% against S. pneumoniae and from 78% to 86% against H. influenzae. CFR was always >85% with amoxicillin/clavulanate. With the 3-day ceftriaxone regimen, the probability of achieving free concentrations above MIC at 72 hours significantly increased compared to the single dose, with which CFR ranged from 70% to 84%.. High-dose amoxicillin (at least 80 mg/kg/day) should be the first-line therapy in uncomplicated infections, whereas amoxicillin/clavulanate (40 mg/kg/day) should be the choice when additional coverage for H. influenzae is desired. Administration of 3 daily doses of ceftriaxone increases bacteriological eradication probability when compared with one-day regimen, although additional clinical evaluations are necessary to establish the best target attainment with ceftriaxone.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; beta-Lactam Resistance; Ceftriaxone; Child; Computer Simulation; Dose-Response Relationship, Drug; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Monte Carlo Method; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae

Topics: Aged; Anti-Bacterial Agents; Bacteriological Techniques; Blood; Ceftriaxone; Ciprofloxacin; Drug Therapy, Combination; Francisella tularensis; Gentamicins; Humans; Immunocompromised Host; Kidney Transplantation; Male; Pneumococcal Infections; Tularemia

Daptomycin is a novel lipopeptide antibiotic with excellent activity against Gram-positive bacterial pathogens, but its therapeutic value for the treatment of invasive pneumococcal disease compared to that for the treatment of pneumococcal pneumonia is incompletely defined. We investigated the efficacy of daptomycin in two models of Streptococcus pneumoniae-induced lung infection, i.e., pneumococcal pneumonia and septic pneumococcal disease. Mice were infected with a bioluminescent, invasive serotype 2 S. pneumoniae strain or a less virulent serotype 19 S. pneumoniae strain and were then given semitherapeutic or therapeutic daptomycin or ceftriaxone. Readouts included survival; bacterial loads; and septic disease progression, as determined by biophotonic imaging. Semitherapeutic daptomycin treatment fully protected the mice against the progression of septic disease induced by serotype 2 S. pneumoniae, while therapeutic treatment of the mice with daptomycin or ceftriaxone led to approximately 70% or approximately 60% survival, respectively. In contrast, mice infected with serotype 19 S. pneumoniae developed severe pneumonia and lung leakage even in the presence of increased intra-alveolar daptomycin levels, resulting in only 40% survival, whereas the ceftriaxone-treated mice had 100% survival. Together, although daptomycin demonstrates little efficacy in the treatment of pneumococcal pneumonia, daptomycin is highly effective in preventing S. pneumoniae-induced septic death, thus possibly offering a therapeutic option for patients with life-threatening septic pneumococcal disease.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Daptomycin; Disease Models, Animal; Mice; Mice, Inbred C57BL; Pneumococcal Infections; Pneumonia, Pneumococcal; Sepsis; Streptococcus pneumoniae

Topics: Anti-Infective Agents; Aortic Valve; Aortic Valve Insufficiency; Aza Compounds; Blindness; Ceftriaxone; Cough; Echocardiography, Transesophageal; Endophthalmitis; Fever; Fluoroquinolones; Hearing Loss, Sensorineural; Heart Valve Prosthesis; Humans; Male; Middle Aged; Mitral Valve; Moxifloxacin; Pneumococcal Infections; Quinolines; Streptococcus pneumoniae; Vancomycin; Vision Disorders

P4, a 28-amino-acid peptide, is a eukaryotic cellular activator that enhances specific in vitro opsonophagocytic killing of multiple bacterial pathogens. In a previous study, we successfully recreated this phenomenon in mice in vivo by using a two-dose regimen of P4 and pathogen-specific antibodies, which significantly reduced moribundity in mice. For the present study, we hypothesized that the inclusion of a low-dose antibiotic would make it possible to treat the infected mice with a single dose containing a mixture of P4 and a pathogen-specific antibody. A single dose consisting of P4, intravenous immunoglobulin (IVIG), and ceftriaxone effectively reduced moribundity compared to that of untreated controls (n = 10) by 75% (P < 0.05) and rescued all (10 of 10) infected animals (P < 0.05). If rescued animals were reinfected with Streptococcus pneumoniae and treated with a single dose containing P4, IVIG, and ceftriaxone, they could be rerescued. This observation of the repeated successful use of P4 combination therapy demonstrates a low risk of tolerance development. Additionally, we examined the polymorphonuclear leukocytes (PMN) derived from infected mice and observed that P4 enhanced in vitro opsonophagocytic killing (by >80% over the control level; P < 0.05). This finding supports our hypothesis that PMN are activated by P4 during opsonophagocytosis and the recovery of mice from pneumococcal infection. P4 peptide-based combination therapy may offer an alternative and rapid immunotherapy to treat fulminant pneumococcal infection.

Topics: Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Bacterial Proteins; Ceftriaxone; Drug Therapy, Combination; Female; Immunization, Passive; Immunoglobulins, Intravenous; Immunologic Factors; Mice; Neutrophils; Peptides; Phagocytosis; Pneumococcal Infections; Streptococcus pneumoniae; Survival Analysis

Throat cultures from an adult pharyngitis patient yielded Streptococcus pneumoniae as a single organism, with a very high bacterial count. The isolate was found to be macrolide and fluoroquinolone resistant, and the same strain was cultured from the patient's denture washing solution. Ceftriaxone therapy, a gradual reduction in the bacterial count and progressive clinical improvement proceeded at the same pace, so we labelled this clinical case as a pneumococcal pharyngitis.

Topics: Aged; Anti-Bacterial Agents; Ceftriaxone; Female; Humans; Pharyngitis; Pneumococcal Infections; Streptococcus pneumoniae

About 2% of childhood episodes of invasive pneumococcal disease (IPD) are recurrent, and most remain unexplained.. To report two cases of otherwise healthy, unrelated children with recurrent IPD as the only clinical infectious manifestation of an inherited disorder in nuclear factor-kappaB(NF-kappaB)-dependent immunity.. One child carried two germline mutations in IRAK4, and had impaired cellular responses to interleukin (IL)1 receptor and toll-like receptor (TLR) stimulation. The other child carried a hemizygous mutation in NEMO, associated with a broader impairment of NF-kappaB activation, with an impaired cellular response to IL-1R, TLR and tumour necrosis factor receptor stimulation. The two patients shared a narrow clinical phenotype, associated with two related but different genotypes.. Otherwise healthy children with recurrent IPD should be explored for underlying primary immunodeficiencies affecting the IRAK4-dependent and NEMO-dependent signalling pathways.

Topics: Anti-Bacterial Agents; Antibody Formation; Ceftriaxone; Child; Child, Preschool; DNA, Complementary; Exons; Humans; I-kappa B Kinase; Immunologic Deficiency Syndromes; Interleukin-1; Interleukin-1 Receptor-Associated Kinases; Introns; Male; NF-kappa B; Pneumococcal Infections; Pneumococcal Vaccines; Polymerase Chain Reaction; Recurrence; Signal Transduction; Streptococcus pneumoniae

Experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), can be aggravated by a mild Streptococcus pneumoniae infection. This study was performed to assess whether treatment with antibiotics inhibiting bacterial protein synthesis reduces the detrimental effect of infection on the course of EAE.. In vitro, release of proinflammatory pneumococcal products was studied by enzyme immunoassay and western blot. Seven days after induction of EAE (prior to the onset of symptoms) mice were infected intraperitoneally with S. pneumoniae and treated either with the inhibitors of bacterial protein synthesis minocycline or rifampicin, or with the beta-lactam ceftriaxone.. During bacterial killing in vitro, minocycline and rifampicin released lower quantities of proinflammatory bacterial products from S. pneumoniae than ceftriaxone. Mice treated with minocycline developed symptoms of EAE 1 day later than mice treated with ceftriaxone. Neither minocycline nor rifampicin therapy, however, reduced the severity of EAE in comparison with ceftriaxone treatment.. Although statistically significant (P = 0.04), a delay of 1 day in the onset of symptoms of EAE after minocycline treatment is of minor clinical relevance. These data do not support the hypothesis of superiority of a bacterial protein synthesis inhibitor over a beta-lactam antibiotic for the treatment of concomitant infections during the latent phase of EAE or MS.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Encephalomyelitis, Autoimmune, Experimental; Female; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Minocycline; Pneumococcal Infections; Rifampin; Teichoic Acids

Pneumococcal cellulitis is an uncommon infection. Head, neck, and trunk are usually affected in patients with hematological malignancies and lupus erythematosus. Limb cellulitis is frequently observed in patients with diabetes mellitus, drug abusers, or alcoholics. Patients present with septic shock most of the time. Surgical treatment is necessary in 50% of the cases. The outcome is usually favorable. We describe the case of a 72-year-old alcoholic patient with diabetes mellitus presenting with cellulitis and septic shock. Serotype 19 Streptococcus pneumoniae with abnormal susceptibility to penicillin (MIC: 0.75 mg/l) was isolated from cellulitis and in blood culture. The evolution was favorable after itavenous antibiotherapy combining ceftriaxone(DCI) (2 g/j), metronidazole(DCI) (1 g/j), and ciprofloxacin(DCI).

Topics: Aged; Ceftriaxone; Cellulitis; Ciprofloxacin; Diabetes Complications; Humans; Male; Metronidazole; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae

Streptococcus (S.) pneumoniae meningitis has a high lethality despite antibiotic treatment. Inflammation is a major pathogenetic factor, which is unresponsive to antibiotics. Therefore adjunctive therapies with antiinflammatory compounds have been developed. TNF484 is a TNF-alpha converting enzyme (TACE) inhibitor and has been found efficacious in experimental meningitis. Toll-like receptor 2 (TLR2) contributes to host response in pneumococcal meningitis by enhancing bacterial clearing and downmodulating inflammation. In this study, TNF484 was applied in mice, which lacked TLR2 and exhibited a strong meningeal inflammation.. 103 CFU S. pneumoniae serotype 3 was inoculated subarachnoidally into C57BL/6 wild type (wt) mice or TLR2-/-, CD14-/- and CD14-/-/TLR2-/- mice. Severity of disease and survival was followed over 9 days. Response to antibiotics (80 mg/kg ceftriaxone i.p. for 5 days) and/or TACE inhibitor treatment (1 mg/kg s.c. twice daily for 4 days) was evaluated. Animals were sacrificed after 12, 24, and 48 h for analysis of bacterial load in cerebrospinal fluid (CSF) and brain and for TNF and leukocyte measurements in CSF.. TLR2-/- mice were significantly sicker than the other mouse strains 24 h after infection. All knockout mice showed higher disease severity after 48 h and died earlier than wt mice. TNF release into CSF was significantly more elevated in TLR2-/- than in the other strains after 24 h. Brain bacterial numbers were significantly higher in all knockout than wt mice after 24 h. Modulation of outcome by antibiotic and TACE inhibitor treatment was evaluated. With antibiotic therapy all wt, CD14-/- and TLR2-/-/CD14-/- mice, but only 79% of TLR2-/- mice, were rescued. TACE inhibitor treatment alone did not rescue, but prolonged survival in wt mice, and in TLR2-/- and CD14-/- mice to the values observed in untreated wt mice. By combined antibiotic and TACE inhibitor treatment 95% of TLR2-/- mice were rescued.. During pneumococcal meningitis strong inflammation in TLR2-deficiency was associated with incomplete responsiveness to antibiotics and complete response to combined antibiotic and TACE inhibitor treatment. TACE inhibitor treatment offers a promising adjuvant therapeutic strategy in pneumococcal meningitis.

Topics: ADAM Proteins; ADAM17 Protein; Animals; Anti-Bacterial Agents; Ceftriaxone; Chemotherapy, Adjuvant; Female; Hydroxamic Acids; Lipopolysaccharide Receptors; Male; Meningitis, Pneumococcal; Mice; Mice, Inbred C57BL; Mice, Knockout; Pneumococcal Infections; Streptococcus pneumoniae; Toll-Like Receptor 2; Tumor Necrosis Factor-alpha

Recurrent systemic pneumococcal infection usually occurs in immunocompromised patients and patients with underlying conditions.. Between 1993 and 2006, investigators at 8 pediatric hospitals prospectively identified cases of invasive pneumococcal disease (IPD) and retrospectively documented demographics and clinical information. Antibiotic susceptibility was determined for penicillin and ceftriaxone by microbroth dilution. Isolates were serotyped and molecular relatedness determined using pulse field gel electrophoresis (PFGE).. Four thousand sixty-seven children were diagnosed with IPD over 12.3 years. One hundred and 8 episodes of recurrent disease were seen in 90 children (2.6%); 75 experienced 2 infections, 12 experienced 3 infections and 3 experienced 4 infections. Fourteen of the 15 children with >2 episodes of infection had underlying conditions. The mean duration between 1st and 2nd infection was 22.9 weeks for children with no known underlying condition and 43.0 weeks for children with an underlying condition (P = 0.001). Seventy episodes of IPD among the 90 patients were caused by a different serotype or a different genotype as demonstrated by the PFGE. Sixteen children had intervals <30 days between infections; 7 were caused by different strains.. Approximately 80% of the children with recurrent invasive pneumococcal disease had underlying conditions. Seven of 16 children with recurrent infection <30 days apart were caused by acquisition of a new strain. Relapse of infection requires documentation that the pneumococcal isolates are not only the same serotype but also have the same PFGE patterns.

Topics: Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Cellulitis; Child; Child, Preschool; DNA Fingerprinting; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Genotype; Humans; Immunocompromised Host; Infant; Male; Microbial Sensitivity Tests; Penicillins; Pneumococcal Infections; Pneumonia, Pneumococcal; Recurrence; Serotyping; Streptococcus pneumoniae

The rate of nonsusceptibility of penicillin-resistant Streptococcus pneumoniae strains to ceftriaxone increased significantly in Taiwan in 2005. Approximately 90% of the ceftriaxone-nonsusceptible isolates were found to be of four major serotypes (serotypes 6B, 14, 19F, and 23F). Seven amino acid alterations in the penicillin-binding protein 2B transpeptidase-encoding region specifically contributed to the resistance.

Topics: Amino Acid Substitution; Aminoacyltransferases; Anti-Bacterial Agents; Ceftriaxone; DNA Primers; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Humans; Penicillin Resistance; Penicillin-Binding Proteins; Pneumococcal Infections; Reverse Transcriptase Polymerase Chain Reaction; Streptococcus pneumoniae; Taiwan

A 10-kg 9-month-old infant with recurrent, unresponsive otitis media presented with bilateral acute otitis media caused by Streptococcus pneumoniae type 19A, resistant to all oral agents and intermediately susceptible to ceftriaxone. Treatment with myringotomies and intramuscular ceftriaxone, 50 mg/kg/d for 5 days, was unsuccessful. The patient responded to pressure equalization tubes and local ciprofloxacin with dexamethasone drops.

Topics: Anti-Bacterial Agents; Ceftriaxone; Cephalosporin Resistance; Ear, Middle; Humans; Infant; Injections, Intramuscular; Male; Otitis Media; Pneumococcal Infections; Streptococcus pneumoniae; Treatment Failure

The infectious or inflammatory nature of an aortitis is difficult to assert because the microbiological results are often negative. The development of an aneurysm under treatment is rare, but requires a change in the therapeutic strategy and the etiologic diagnosis needs to be discussed again.. We report the case of a 69-year-old woman treated by corticotherapy for an aortitis thought to be inflammatory, who required emergency surgery when a dissected aneurysm appeared. The peroperative samples were positive to Streptococcus pneumoniae using polymerase chain reaction and allowed a change of the diagnosis. The patient evolved favorably under antibiotic therapy.. The decision to treat an aortitis by corticotherapy must be made with caution even if the microbiological tests are negative.

Topics: Adrenal Cortex Hormones; Aged; Anti-Bacterial Agents; Aortic Aneurysm, Abdominal; Aortic Dissection; Aortitis; Ceftriaxone; Drug Therapy, Combination; Emergencies; Female; Follow-Up Studies; Gentamicins; Humans; Ofloxacin; Pneumococcal Infections; Streptococcus pneumoniae; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

A total of 522 Streptococcus pneumoniae invasive isolates from diverse sources were collected from January 2002 to December 2003 in Taiwan in order to understand the serotype distribution of invasive isolates in Taiwan. The most frequently isolated serotypes of S. pneumoniae were types 14 (18.4%), 23F (15.1%), 3 (13.8%), 19F (13.4%), 6B (8.2%), 9V (3.6%) and 4 (2.5%). The majority of cases were either under 5 years of age (24.1%) or older than 65 years (36.6%). Serotype distribution in adults aged over 14 years and children aged under 2 years was similar, except for that of type 3, which was more prevalent in adults. Penicillin-non-susceptible strains accounted for 67.7% of all strains and were the predominant strains of serotypes 23F, 19F, 6B and 14. Most strains were susceptible to cephem drug, 85.7% of isolates were susceptible to cefotaxime and 92.9% were susceptible to ceftriaxone. A total of 72.6% (379/522) of the isolates were resistant to at least two antibiotics. The 23-valent vaccine in the current commercial market would cover 87.2% of the serotypes and 100% of the penicillin-non-susceptible serotypes of S. pneumoniae in Taiwan. The coverage of 7- and 11-valent protein conjugate vaccines of the serotypes in children under 2 years of age would be 78.8 and 86.5%, respectively. These results will help to assess the adequacy of the vaccine formulations marketed in Taiwan.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Proteins; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Humans; Infant; Microbial Sensitivity Tests; Middle Aged; Penicillin Resistance; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Population Surveillance; Serotyping; Streptococcus pneumoniae; Taiwan; Vaccines, Conjugate

A large international collection of Streptococcus pneumoniae (21605 strains) was analyzed to determine the comparative activity of selected oral (cefuroxime and cefpodoxime) and parenteral (ceftriaxone and cefepime) cephalosporins when tested against different antimicrobial resistance phenotypes including penicillin-resistant strains and strains displaying additional resistances to other agents (erythromycin, clindamycin, tetracycline, and trimethoprim/sulfamethoxazole). The multidrug-resistant (MDR) rate ranged from 17.6% (penicillin- and erythromycin-resistant only) to 5.7% (resistance to all 5 drugs). The parenteral cephalosporins retained wider activity for all MDR phenotypes studied with the resistance rates (minimum inhibitory concentration > or = 4 mug/mL) being lower for cefepime (1.3-1.9%) when compared with ceftriaxone (3.0-4.4%) or the orally administered cephalosporins, cefpodoxime (64.4-74.1%), and cefuroxime (69.3-79.1%). Our findings confirm that the parenteral cephalosporins, cefepime, and ceftriaxone possess significant activity against those MDR pneumococci responsible for an increasing number of serious respiratory tract infections.

Topics: Administration, Oral; Cefepime; Ceftriaxone; Cephalosporin Resistance; Cephalosporins; Cohort Studies; Drug Resistance, Multiple, Bacterial; Female; Humans; Infusions, Intravenous; International Cooperation; Male; Microbial Sensitivity Tests; Pneumococcal Infections; Sensitivity and Specificity; Streptococcus pneumoniae

We report the unusual involvement of altered PBP 2A in the development of beta-lactam resistance in Streptococcus pneumoniae. This was investigated amid three identical serotype 14 isolates (designated isolates 1, 2, and 3, respectively) of pneumococci cultured successfully from the blood of a human immunodeficiency virus-seropositive child with recurrent pneumonia. The passage of this strain through its human host induced several changes in the bacterium, which is typical of the adaptive and evolving nature of the pneumococcus. An efflux resistance mechanism, which conferred increased ciprofloxacin resistance, was induced in isolates 2 and 3. In addition, faster growth rates and larger capsules were also observed for these isolates, with respect to isolate 1. Notably, compared to isolates 1 and 2, isolate 3 showed a decrease in penicillin, cefotaxime, and ceftriaxone resistance. This change was associated with the replacement of an altered PBP 2A for an unaltered PBP 2A. In all likelihood, these events produced a strain which evolved into a fitter and more virulent type, isolate 3, that resulted in an aggravated pneumococcal infection and ultimately in the patient's death.

Topics: Cefotaxime; Ceftriaxone; Cephalosporin Resistance; Child; DNA, Bacterial; Female; Genotype; HIV Seropositivity; Humans; Microscopy, Phase-Contrast; Molecular Sequence Data; Penicillin Resistance; Penicillin-Binding Proteins; Peptide Synthases; Pneumococcal Infections; Reverse Transcriptase Polymerase Chain Reaction; Streptococcus pneumoniae; Transformation, Genetic

A previously healthy eight-month-old infant presented with shortness of breath and pyrexia. He was found to have purulent pericarditis due to Streptococcus pneumoniae, complicated by acute renal failure due to haemolytic uraemic syndrome. He received peritoneal dialysis and recovered with normalisation of renal function. This case highlights two important complications of pneumococcal infection in one individual and illustrates the need for rapid diagnosis and treatment of invasive pneumococcal disease. It is anticipated that introduction of the conjugate pneumococcal vaccination to the Australian Standard Vaccination Schedule from 2005 will reduce the incidence of pneumococcal infection and its associated morbidity and mortality.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Ceftriaxone; Follow-Up Studies; Hemolytic-Uremic Syndrome; Humans; Infant; Male; Pericarditis; Peritoneal Dialysis; Pneumococcal Infections; Streptococcus pneumoniae; Suppuration

To compare the in vitro and in vivo activity of penicillin, cefotaxime and ceftriaxone, using three strains of Streptococcus pneumoniae with different susceptibilities to penicillin (MICs of 0.015, 0.25 and 2 mg/L, respectively).. Time-kill curves and an experimental model of endocarditis in rabbits.. Penicillin was efficacious in clearing bacteria from vegetations and blood irrespective of whether infections were caused by penicillin-susceptible or penicillin-resistant strains (P < 0.01 with respect to control groups). The same efficacy was shown with cefotaxime and ceftriaxone. Comparing the results of the in vivo model with those obtained in time-kill curves, penicillin showed the best results.. These results confirm that penicillin is efficacious in the treatment of pneumococcal infections, including those produced by strains with MICs < or = 2 mg/L (with the exception of pneumococcal meningitis). These results also suggest that the breakpoints to define susceptibility and resistance of S. pneumoniae to penicillin must be reviewed, as has been done with amoxicillin and third-generation cephalosporins.

Topics: Animals; Anti-Bacterial Agents; beta-Lactams; Cefotaxime; Ceftriaxone; Endocarditis, Bacterial; Half-Life; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Pneumococcal Infections; Rabbits; Streptococcus pneumoniae

Topics: Adult; Alanine Transaminase; Anti-Bacterial Agents; Aspartate Aminotransferases; Ceftriaxone; Critical Care; Hepatocytes; Humans; Liver Function Tests; Male; Pneumococcal Infections

A 65-year-old previously healthy man was referred because of high fever, progressive dyspnea and retrosternal pain for 2 days. On admission, the patient was already in a reduced general condition, blood pressure was 120/70 mmHg, heart rate irregular at 75/min and temperature at 39.7 degrees C. Auscultation of the heart revealed distant heart sounds, murmurs were not present, but mild rales were heard over both lung bases. Jugular veins were congested.. ECG showed a generalized ST-segment elevation with preserved R-waves, slightly depressed PR-segment and atrial bigemini. Chest X-ray revealed an enlarged cardiac silhouette with signs of a pneumopericardium. Transthoracic echocardiography showed a circular pericardial effusion and haemodynamic impairment. Percutaneous pericardiocentesis revealed a purulent effusion with microbiological proof of pneumococci. The primary infectious focus was a maxillary sinusitis caused by pneumococci.. Bacterial pericarditis due to by haematogenous spread of pneumococci.. Antibiotic therapy consisted of intravenous ceftriaxon and gentamicin. To rinse the pericardial space and drain the thick, purulent effusion subxiphoidal, pericardiocentesis and insertion of a drainage tube were done. Physiological saline was put into the pericardial space several times a day, drained and analysed microbiologically. In the meantime rinsing of the infected maxillary sinus was performed. Transthoracic echocardiography was done repeatedly to rule out complications of bacterial pericarditis, especially constrictive pericarditis. The pericardial tube was removed after proof of a sterile drainage 9 days after insertion. The patient was discharged after 4 weeks of hospitalization without clinical or echocardiographic signs of diastolic dysfunction.. Suspected bacterial pericarditis must be treated as an emergency and confirmed or ruled out by percutaneous pericardiocentesis.

Topics: Aged; Ceftriaxone; Diagnosis, Differential; Diagnostic Imaging; Dyspnea; Fever of Unknown Origin; Follow-Up Studies; Gentamicins; Humans; Male; Maxillary Sinusitis; Microbial Sensitivity Tests; Pericarditis; Pneumococcal Infections; Suction; Therapeutic Irrigation

Time above MIC (T>MIC) is regarded as the best pharmacokinetic/pharmacodynamic (PK/PD) parameter for predicting the clinical efficacy of cephalosporins. The concentration of non-protein-bound proprietary ceftriaxone (Rocephin, Roche) in body fluids exceeds this PK/PD criterion for the treatment of Streptococcus pneumoniae respiratory infections. However, the pharmaceutical quality of several generic products may be inferior to Rocephin. We have calculated the variations in fluid concentrations of 34 generic formulations of ceftriaxone and, by mathematical modelling, the implications for attainment of recommended PK/PD criteria, specifically: Treatment of S. pneumoniae infections based on the time that non-protein-bound ceftriaxone concentration in pleural fluid exceeds the CLSI (NCCLS) breakpoint of 4 mg/L for identification of resistant isolates. Impact upon Monte Carlo simulations in plasma for the treatment of S. pneumoniae infections based on T>MIC for 50% dosing interval. Rocephin exceeded the required PK/PD parameters at the mean and two standard deviation levels in both investigations. In contrast, most generic products failed to achieve required PK/PD levels in both investigations. As a consequence, some generic formulations of ceftriaxone may increase risks of clinical failure and/or emergence of resistant isolates.

Topics: Anti-Bacterial Agents; Ceftriaxone; Drug Resistance, Bacterial; Forecasting; Humans; Microbial Sensitivity Tests; Models, Theoretical; Monte Carlo Method; Pneumococcal Infections; Risk Factors; Streptococcus pneumoniae; Therapeutic Equivalency; Treatment Outcome

High-level penicillin resistance has been associated with treatment failure in patients with Streptococcus pneumoniae infections. To identify a subgroup of patients at low risk for high-level penicillin-nonsusceptible S. pneumoniae bacteremia, a cross-sectional study of 303 patients was performed. For the total study population, penicillin resistance was observed in 98 (32%) of 303 patients; high-level resistance was seen in 33 (11%). A predictive model was created by using 3 baseline variables that were independently associated with high-level penicillin resistance: previous beta -lactam antibiotic use, previous stay in a risk area (defined as stay in day care facilities, prisons, homeless shelters, nursing homes, or other long-term care facilities), and previous respiratory tract infection. The model was used to identify patients at low and high risk for high-level penicillin-resistant pneumococcal bacteremia. None of the isolates of patients in the low-risk subgroup had ceftriaxone resistance. Patients in the low-risk subgroup could be empirically treated with fluoroquinolone-sparing regimens.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Cross-Sectional Studies; Drug Resistance, Bacterial; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Penicillin Resistance; Penicillins; Pneumococcal Infections; Retrospective Studies; Risk Factors; Streptococcus pneumoniae

Infections of major vessels leading to mycotic aneurysms can be a diagnostic dilemma for clinicians, and can be accompanied by a high mortality rate. Successful treatment of this condition often requires a high index of suspicion and prompt medical and surgical attention. The authors report two cases of infectious aortitis caused by pneumococcus that evolved during hospitalization, and discuss diagnostic difficulties that accompany this entity.

Topics: Aged; Anti-Bacterial Agents; Aortic Aneurysm; Aortitis; Ceftriaxone; Female; Humans; Male; Middle Aged; Pneumococcal Infections

Topics: Cefotaxime; Ceftriaxone; Cephalosporins; Humans; Microbial Sensitivity Tests; Pneumococcal Infections; Reference Standards; Streptococcus pneumoniae

We compared the activities of telithromycin, erythromycin, azithromycin, josamycin, penicillin G, amoxicillin, cefpodoxime, and ceftriaxone against invasive and noninvasive non-penicillin-susceptible Streptococcus pneumoniae isolates recovered from children. Of the 186 isolates tested, 89% were positive for erm(B) by PCR. Telithromycin had the lowest MICs, with MICs at which 90% of the isolates tested are inhibited of 0.032 and 0.25 micro g/ml for erythromycin-sensitive and -resistant isolates, respectively.

Topics: Amoxicillin; Anti-Bacterial Agents; Azithromycin; Cefpodoxime; Ceftizoxime; Ceftriaxone; Child; Drug Resistance, Bacterial; Erythromycin; France; Humans; In Vitro Techniques; Josamycin; Ketolides; Macrolides; Penicillin G; Penicillin Resistance; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae

To determine the prevalence of penicillin resistance and molecular characteristics of pneumococcal isolates at the University of Malaya Medical Center.. From March 1999 to July 2000, 100 clinical isolates of Streptococcus pneumoniae were obtained from 93 patients of various ages and from various body sites. The minimum inhibitory concentrations (MICs) for penicillin and ceftriaxone were determined by E test, and results were interpreted according to guidelines recommended by the National Committee for Clinical Laboratory Standards (NCCLS). Fifty isolates were further serotyped, and analyzed by pulsed-field gel electrophoresis (PFGE) and polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) of the penicillin-binding protein (pbp) 2b and 2x genes.. The majority of the isolates were from respiratory sites. Thirty-one isolates showed decreased susceptibility to penicillin (PRSP), and many of these also showed decreased susceptibility to ceftriaxone. Twelve serogroup/types (SGTs) were present, with 19F being the most common. PFGE analysis identified two dominant profiles, consisting mainly of PRSPs that had common serotypes (19F) and pbp gene patterns within their respective groups, although PCR-RFLP analysis showed different patterns of pbp genes among the PRSPs as compared to penicillin-susceptible strains, which had a uniform pattern.. PRSPs were genetically related as shown by PFGE and serotype. The consistency of pbp gene patterns, observed among many of the PRSPs within their respective PFGE profiles, supported their relatedness as established by PFGE.

Topics: Academic Medical Centers; Anti-Bacterial Agents; Bacterial Proteins; Carrier Proteins; Ceftriaxone; Electrophoresis, Gel, Pulsed-Field; Hexosyltransferases; Humans; Malaysia; Microbial Sensitivity Tests; Muramoylpentapeptide Carboxypeptidase; Penicillin Resistance; Penicillin-Binding Proteins; Penicillins; Peptidyl Transferases; Pneumococcal Infections; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Prevalence; Serotyping; Streptococcus pneumoniae

The nasopharyngeal carriage of Streptococcus pneumoniae is an important risk factor for pneumococcal diseases. Data regarding prevalence and serotype distribution of this pathogen are lacking in our population.. longitudinal observational cohort study.. healthy children aged 1-7 years attending day-care centers and schools of a district of a Southern Italy city.. the nasopharyngeal colonization rate of Streptococcus pneumoniae as well as its antibiotic susceptibility was determined.. Of 317 nasopharyngeal cultures obtained, 18.29% of the cultures were positive for Streptococcus pneumoniae; 60.34% of the isolates were serotypes 19A, 19F, 14, 6B, or 23F; 8.62% of the strains were intermediately resistant to penicillin. Erythromycin-resistance was observed in 65.51% of the micro-organisms isolated and particularly serotypes 19, 14, and 6 were more erythromycin-resistant than organisms of other serotypes. Co-trimoxazole resistance was detected in 17.24% of the strains. All the strains resulted uniformly susceptible to cefotaxime and ceftriaxone.. The high rate of nasopharyngeal carriage of Streptococcus pneumoniae, along with the resistance to antibiotics widely used in the community, suggests the importance of an epidemiological surveillance as well as the application of new vaccine strategies.

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Cohort Studies; Drug Resistance, Bacterial; Erythromycin; Female; Humans; Infant; Italy; Longitudinal Studies; Male; Microbial Sensitivity Tests; Nasopharynx; Pneumococcal Infections; Serotyping; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination

To evaluate the clinical relevance of cephalosporin (ceftriaxone/cefotaxime) resistance among patients with nonmeningeal systemic pneumococcal infection.. From January 1994 to October 2000, we prospectively studied 522 episodes of nonmeningeal systemic pneumococcal infections (448 pneumonias) in 499 adults who were treated according to hospital guidelines. In vitro antibiotic susceptibility, as the minimum inhibitory concentration (MIC), was determined by microdilution method. The MIC methods and breakpoints (cutoffs) were established by the National Committee for Clinical Laboratory Standards.. Of the 522 pneumococcal strains, 413 strains (79%) were susceptible to ceftriaxone/cefotaxime, MIC < or =0.5 microg/mL; 79 (15%) were intermediate, MIC = 1 microg/mL; and 30 (6%) were resistant, MIC = 2 microg/mL. After adjusting for several variables, including pneumococcal serogroups/serotypes, infections due to nonsusceptible (intermediate and resistant) pneumococcal strains were independently associated with prior antibiotic therapy, with an odds ratio of 5.9 (95% confidence interval: 2.6 to 13.6). Thirty-day mortality among the 185 patients who were treated with ceftriaxone (1 g/d) or cefotaxime (1.5 g every 8 hours) did not differ by cephalosporin susceptibility: 18% (26/148) among those with susceptible organisms, 13% (3/24) with intermediate organisms, and 15% (2/13) in resistant cases (P = 0.81).. Ceftriaxone or cefotaxime were effective in treating patients with nonmeningeal systemic pneumococcal infections caused by strains with MIC < or =2 microg/mL. These results support the newly established ceftriaxone/cefotaxime MIC breakpoints (cutoffs) for nonmeningeal pneumococcal infections.

Topics: Adult; Aged; Bacteremia; Cefotaxime; Ceftriaxone; Cephalosporin Resistance; Cohort Studies; Female; Humans; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Pneumococcal Infections; Probability; Prospective Studies; Risk Assessment; Streptococcus pneumoniae; Survival Analysis; Treatment Outcome

Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacterial wall components. TLR2 function was investigated in a murine Streptococcus pneumoniae meningitis model in wild-type (wt) and TLR2-deficient (TLR2(-/-)) mice. TLR2(-/-) mice showed earlier time of death than wt mice (P<.02). Plasma interleukin-6 levels and bacterial numbers in blood and peripheral organs were similar for both strains. With ceftriaxone therapy, none of the wt but 27% of the TLR2(-/-) mice died (P<.04). Beyond 3 hours after infection, TLR2(-/-) mice had higher bacterial loads in brain than did wt mice, as assessed with luciferase-tagged S. pneumoniae by means of a Xenogen-CCD (charge-coupled device) camera. After 24 h, tumor necrosis factor activity was higher in cerebrospinal fluid of TLR2(-/-) than wt mice (P<.05) and was related to increased blood-brain barrier permeability (Evans blue staining, P<.02). In conclusion, the lack of TLR2 was associated with earlier death from meningitis, which was not due to sepsis but to reduced brain bacterial clearing, followed by increased intrathecal inflammation.

Topics: Animals; Ceftriaxone; Cephalosporins; Disease Models, Animal; Disease Susceptibility; Drosophila Proteins; Inflammation; Listeria monocytogenes; Listeriosis; Membrane Glycoproteins; Meningitis, Bacterial; Mice; Mice, Inbred C57BL; Mice, Knockout; Pneumococcal Infections; Receptors, Cell Surface; Streptococcus pneumoniae; Time Factors; Toll-Like Receptor 2; Toll-Like Receptors

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.

Topics: Adolescent; Anti-Bacterial Agents; Case-Control Studies; Ceftriaxone; Child; Child, Preschool; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Pneumococcal Infections; Prognosis; Retrospective Studies; Risk Factors; Streptococcus pneumoniae

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Ceftriaxone; Child, Preschool; Combined Modality Therapy; Drug Therapy, Combination; Erythrocyte Transfusion; Hemolytic-Uremic Syndrome; Humans; Incidence; Male; Pneumococcal Infections; Prognosis; Risk Factors; Severity of Illness Index; Treatment Outcome

We report a case of purpura fulminans associated with drug-resistant Streptococcus pneumoniae that responded to ceftriaxone therapy. Ultrasonography of the abdomen and splenic scan revealed the absence of a spleen.

Topics: Ceftriaxone; Cephalosporins; Drug Resistance; Female; Humans; IgA Vasculitis; Infant; Pneumococcal Infections; Recurrence; Spleen

Publication of the NCCLS M100-S12 document in January 2002 introduced ceftriaxone and cefotaxime MIC interpretative breakpoints of < or =1 microg/ml (susceptible), 2 microg/ml (intermediate), and > or =4 microg/ml (resistant) for nonmeningeal isolates of Streptococcus pneumoniae. To estimate the effect of these breakpoint changes on clinical laboratory susceptibility testing results, nonmeningeal pneumococcal isolate (blood and respiratory) data from The Surveillance Network Database-USA, an electronic surveillance database, for the years 1996 to 2000 were collated and studied. Of 9,863 nonmeningeal isolates tested against ceftriaxone, 82.7% were susceptible, 13.2% were intermediate, and 4.1% were resistant by the M100-S11 NCCLS breakpoints (2001); by M100-S12 breakpoints, 95.9% of the isolates were susceptible, 3.1% were intermediate, and 1.0% were resistant. Of 10,777 nonmeningeal isolates tested against cefotaxime, 79.2% were susceptible, 14.3% were intermediate, and 6.5% were resistant by M100-S11 breakpoints; by M100-S12 breakpoints, 93.5% were susceptible, 4.2% were intermediate, and 2.3% were resistant. Overall, the new M100-S12 ceftriaxone and cefotaxime interpretative breakpoints for nonmeningeal isolates of S. pneumoniae decreased the number of isolates interpreted as intermediate by 10% and as resistant by 3 to 4%.

Topics: Anti-Bacterial Agents; Blood; Cefotaxime; Ceftriaxone; Cephalosporins; Databases, Factual; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Pneumococcal Infections; Respiratory System; Streptococcus pneumoniae

Monitor clinical and microbiologic features including antimicrobial susceptibility of invasive pneumococcal infections among children.. A 6-year (September, 1993, through August, 1999) prospective surveillance study of all invasive pneumococcal infections in children.. Infants and children cared for at eight children's hospitals in the United States with culture-proved invasive pneumococcal infection.. During the 6-year period 2581 episodes of invasive pneumococcal infection occurred in 2498 children. Underlying conditions were present in 29% of the children. Of children without an underlying condition, 15% of the total infections occurred in those 25 to 60 months old. As the ages of the children advanced the proportion of cases classified as bacteremia declined, whereas the proportion classified as pneumonia increased. Also, as the ages of the children increased the proportion of isolates in serotypes/serogroups 1, 3 and 23 increased. whereas the proportion for serotype 14 diminished. During the 6 years of the study, there was a significant increase in the percentage of isolates intermediate or resistant to penicillin (P < 0.000001) or intermediate to ceftriaxone (P < 0.002). By the sixth year of the study, 37 and 11% of the isolates were nonsusceptible to penicillin or ceftriaxone, respectively. Antibiotic use in the 30 days before diagnosis of systemic pneumococcal infection occurred in 30 to 35% of the children for each of the 6 years. The overall case-fatality rate for children with systemic pneumococcal infection was 1.56%. Mortality was greatest in children >60 months old and in those with underlying conditions; mortality was not related to antibiotic susceptibility.. The percentage of pneumococcal isolates recovered from children with systemic infection which were intermediate for penicillin or ceftriaxone or resistant to penicillin increased steadily during the 6-year period. There was also a trend toward increasing rates of resistance to ceftriaxone. The age and serogroup/serotype distributions of our patients support the recommendations to consider administration of the seven valent pneumococcal conjugate vaccine for all children 24 to 59 months old, with special consideration for selected groups.

Topics: Age Factors; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Epidemiologic Studies; Female; Humans; Incidence; Infant; Infant, Newborn; Male; Mortality; Penicillin Resistance; Pneumococcal Infections; Population Surveillance; Prospective Studies; Risk Factors; Serologic Tests

The susceptibility of 4009 recent clinical isolates of Streptococcus pneumoniae to gatifloxacin, levofloxacin, ciprofloxacin, penicillin, ceftriaxone and azithromycin was determined. Overall rates of susceptibility to these agents were 99.4, 98.7, 71.2, 55.2, 80.9, and 71.3%, respectively. Resistance to all tested agents was associated with penicillin resistance. Of penicillin nonsusceptible isolates, 36% were resistant. Resistance to the fluoroquinolones was unusual and gatifloxacin generally appeared to be four-fold more active than levofloxacin or ciprofloxacin. Multidrug resistant S. pneumoniae accounted for 6.2% of this sample. The lowest rate of susceptibility to non-fluoroquinolone antibiotics was observed in isolates from the South region of the United States, which appeared to be explained by both the proportion of and the inherently higher MICs of certain types of isolates.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Ceftriaxone; Child; Ciprofloxacin; Female; Fluoroquinolones; Gatifloxacin; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Ofloxacin; Penicillin Resistance; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae; United States

To determine patterns of resistance for isolates of Streptococcus pneumoniae recovered from middle ear fluids of children from eight children's hospitals between September, 1994, and August, 1997.. Data were extracted retrospectively from the medical records of eight children's hospitals. A standardized data form was completed for each episode of pneumococcal infection. Systemic isolates (blood and pleural, synovial and spinal fluids) of S. pneumoniae were collected during the same period. All isolates of S. pneumoniae from each center were sent to a central laboratory. Susceptibility to penicillin and ceftriaxone was determined by microbroth dilution. Organisms were considered nonsusceptible to penicillin if the minimum inhibitory concentration was > or = 0.1 microg/ml and nonsusceptible to ceftriaxone if the minimum inhibitory concentration was > or = 1.0 microg/ml.. S. pneumoniae was recovered from the middle ear fluids of 707 children from all centers during the study period. Thirty-nine (5.5%) were infections recorded at 4 centers which evaluated middle ear fluid only sporadically and were not included in this analysis. The remaining 668 infections reported by the 4 remaining participating hospitals reflect the experience of 608 children. There were 54% boys; 440 (73%) were Caucasian, 111 (18%) were African-American, 38 (6%) were Hispanic and for 19 (3%) the race was not recorded. The children ranged in age from 16 days to 13.8 years with a mean (+/-sD) of 26.0 (+/- 26.1) months. Children who received antibiotics in the 30 days before the middle ear isolate was recovered were more likely to harbor a resistant strain of S. pneumoniae than children who had not recently received an antibiotic (P < 0.001). Isolates recovered from children with spontaneous otorrhea were more likely to be susceptible to penicillin than isolates recovered during myringotomy, with or without the insertion of tympanostomy tubes (P < 0.01). There was wide variation in the susceptibility of middle ear isolates to penicillin and ceftriaxone according to geographic location; however, in every locale the middle ear isolates were less likely to be susceptible to penicillin and ceftriaxone than systemic isolates of S. pneumoniae.. The prevalence of penicillin-resistant and cephalosporin-resistant S. pneumoniae in middle ear isolates derived from children cared for at four different children's hospitals was quite variable. In some locations the prevalence of resistance is still increasing, whereas in other areas the rate of resistance was at a plateau during the period of surveillance. The prevalence of isolates of S. pneumoniae susceptible to penicillin and ceftriaxone was always less common among middle ear isolates than among systemic isolates. Previous antibiotic use remains the most predictive factor for the recovery of isolates resistant to penicillin and ceftriaxone.

Topics: Acute Disease; Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Otitis Media with Effusion; Penicillin G; Penicillin Resistance; Pneumococcal Infections; Prevalence; Recurrence; Retrospective Studies; Streptococcus pneumoniae; United States

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Clarithromycin; Female; Humans; Meningitis, Pneumococcal; Otitis Media; Pneumococcal Infections; Streptococcal Infections; Streptococcus pneumoniae

The efficacy of different antibiotics was compared in an experimental model of aortic valve endocarditis in rabbits, using a serotype 19 strain of Streptococcus pneumoniae resistant to penicillin (MIC 12 mg/L) and ceftriaxone (MIC 12 mg/L). The results were compared with those of a control group, which received no treatment. One hundred and nineteen animals were treated with one of the following antibiotic regimens: im procaine penicillin G at a dosage of 300,000 U/kg weight/12 h (16 animals); iv trovafloxacin, 13.3 mg/kg/12 h (31 animals); iv ceftriaxone, 75 mg/kg/24 h (21 animals); iv vancomycin, 20 mg/kg/12 h (15 animals) and im quinupristin-dalfopristin, 30 mg/kg/8 h (20 animals). All the antibiotics used in this study proved to be efficient in reducing numbers of S. pneumoniae and in increasing the percentage of aortic vegetations that were rendered sterile compared with the control group. Penicillin at the dosage used in our study was capable of achieving serum concentrations two or three times greater than the MIC, thus demonstrating its effectiveness as an antibiotic for this endocarditis model. No significant difference was observed between the effects of vancomycin, quinupristin-dalfopristin and penicillin. Vancomycin proved to be more efficient than trovofloxacin in reducing the bacterial load and increasing the numbers sterilized. There was also a tendency for this antibiotic to be more effective than ceftriaxone in reducing the bacterial load of the vegetations. There was a statistically significant correlation between the weight of the vegetations and their bacterial load. In the light of these results, vancomycin and quinupristin-dalfopristin may be considered suitable alternatives to penicillin for the treatment of penicillin-resistant S. pneumoniae endocarditis.

Topics: Animals; Anti-Infective Agents; Ceftriaxone; Disease Models, Animal; Drug Resistance, Multiple; Endocarditis, Bacterial; Fluoroquinolones; Humans; Male; Naphthyridines; Penicillin Resistance; Penicillins; Pneumococcal Infections; Rabbits; Streptococcus pneumoniae; Vancomycin; Virginiamycin

To determine the outcome of children treated primarily with beta-lactam antibiotics for a systemic infection outside the central nervous system (CNS) caused by isolates of Streptococcus pneumoniae nonsusceptible to ceftriaxone (MIC > or = 1.0 microg/ml).. Retrospective review of the medical records of children identified prospectively with invasive infections outside of the CNS caused by isolates of S. pneumoniae that were not susceptible to ceftriaxone between September, 1993, and August, 1999. A subset of this group treated primarily with beta-lactam antibiotics was analyzed for outcome.. Infants and children with pneumococcal infections cared for at eight children's hospitals.. Among 2,100 patients with invasive infections outside the CNS caused by S. pneumoniae, 166 had isolates not susceptible to ceftriaxone. One hundred patients treated primarily with beta-lactam antibiotics were identified. From this group 71 and 14 children had bacteremia alone or with pneumonia, respectively, caused by strains with an MIC of 1.0 microg/ml. Bacteremia or pneumonia caused by isolates with a ceftriaxone MIC > or = 2.0 microg/ml occurred in 6 and 5 children, respectively. Three children with septic arthritis and 1 with cellulitis had infections caused by strains with an MIC to ceftriaxone of 1.0 microg/ml. Most were treated with parenteral ceftriaxone, cefotaxime or cefuroxime for one or more doses followed by an oral antibiotic. All but one child were successfully treated. The failure occurred in a child with severe combined immune deficiency and bacteremia (MIC = 1.0 microg/ml) who remained febrile after a single dose of ceftriaxone followed by 12 days of cefprozil.. Ceftriaxone, cefotaxime or cefuroxime are adequate to treat invasive infections outside the CNS caused by pneumococcal isolates with MICs up to 2.0 microg/ml, a concentration currently considered resistant for these antibiotics by National Committee for Clinical Laboratory Standards breakpoints.

Topics: Anti-Bacterial Agents; Bacteremia; Cefotaxime; Ceftriaxone; Cefuroxime; Cephalosporin Resistance; Cephalosporins; Child; Child, Preschool; Humans; Infant; Pneumococcal Infections; Pneumonia, Pneumococcal; Retrospective Studies; Streptococcus pneumoniae

Streptococcus pneumoniae is a common cause of infection in the pediatric population, as well as an important cause of septic arthritis. The increased prevalence of drug-resistant S pneumoniae in North America has renewed interest in the use of pneumococcal vaccines. We describe the case of a child with isolated acute septic arthritis caused by infection with penicillin-resistant S pneumoniae.

Topics: Acute Disease; Anti-Bacterial Agents; Arthritis, Infectious; Ceftriaxone; Cephalosporins; Combined Modality Therapy; Debridement; Drainage; Edema; Elbow Joint; Humans; Infant; Leukocyte Count; Male; Microbial Sensitivity Tests; Nafcillin; Pain; Penicillin Resistance; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Prevalence; Streptococcus pneumoniae

A case report.. To report and discuss a case of pneumococcal vertebral osteomyelitis with meningitis in a previously healthy 51-year-old immunocompetent woman who presented with acute onset lower back pain.. To the authors' knowledge, pneumococcal vertebral osteomyelitis with meningitis in an immunocompetent person with no other predisposing factor has not been reported previously.. The patient was diagnosed to have pneumococcal meningitis 10 days after the onset of acute and severe lower back pain. Significant improvement of clinical symptoms from meningitis was achieved with appropriate antimicrobial treatment. Lumbar CT and MRI scans were performed on persistence of fever and lower back pain. Loss of height and peridiscal inflammation at L3-L4 and epidural and bilateral psoas abscesses were detected.. Diagnosis of pneumococcal vertebral osteomyelitis was established after evaluation of the material obtained from CT-guided aspiration of the psoas abscess and biopsy of the L3 body. With appropriate antimicrobial treatment, the patient's complaints resolved completely.. To the authors' knowledge, this is the first reported case of pneumococcal vertebral osteomyelitis with meningitis.

Topics: Ceftriaxone; Cephalosporins; Female; Humans; Low Back Pain; Lumbar Vertebrae; Meningitis; Middle Aged; Osteomyelitis; Pneumococcal Infections; Spondylolisthesis; Streptococcus pneumoniae; Tomography, X-Ray Computed

The rate of penicillin-resistant Streptococcus pneumoniae isolates in Spain is high. At present, penicillin and ceftriaxone are two drugs chosen for treating serious infections. In this study the bactericidal activity of four antimicrobial regimens against ten clinical isolates of S. pneumoniae (five with an intermediate resistance to penicillin and five highly resistant ones), was determined by means of kill kinetics studies using either penicillin, or ceftriaxone, in combination with vancomycin, or fosfomycin. The concentrations of the antimicrobial regimens (MICs 4x, 1x and 1/4x) were within possible physiological levels. While the combinations of penicillin, or ceftriaxone, plus vancomycin showed a significant increase in bactericidal activity, the bacterial reductions obtained in combination with fosfomycin were greater, achieving synergistic effects. These results suggest that in vivo trials with a regimen composed of ceftriaxone and fosfomycin would be worthwhile.

Topics: Anti-Bacterial Agents; Ceftriaxone; Cephalosporins; Drug Interactions; Drug Therapy, Combination; Fosfomycin; Kinetics; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Pneumococcal Infections; Streptococcus pneumoniae; Vancomycin

Topics: Aged; Aged, 80 and over; Amoxicillin; Ceftriaxone; Cephalosporins; Follow-Up Studies; Humans; Male; Penicillin G; Penicillins; Pericardial Effusion; Pericardiocentesis; Pericarditis; Pneumococcal Infections; Time Factors

The antibiotic susceptibility was analyzed of approximately 400 consecutive isolates of S. pneumoniae isolated from different regions of Saudi Arabia. Most of these isolates were from respiratory (sputum, otitis, 53.8%), blood/CSF (26.3%) and ophthalmic (20%) specimens. Overall 6.2% of the isolates were penicillin-resistant (MICs > or =2 microg/ml) and 51.2% were -intermediate (MICs 0.1-1 microg/ml). The resistance rates to cefuroxime, clarithromycin and ceftriaxone were 14.9%, 14.8% and 4.5% respectively. Only 3.5% of S. pneumoniae showed resistance to amoxycillin/clavulanic acid. The MICs of all tested antibiotics increased as did the penicillin MICs. Penicillin resistance was significantly associated with resistance to cefuroxime (p<0.001) but not with the others. These data indicate the presence of penicillin and multiple-resistant pneumococci in Saudi Arabia and that these strains can spread among individuals. A greater awareness with extended indications for microbiological diagnosis, antimicrobial susceptibility testing and restrictive prescription of antibiotics are needed.

Topics: Amoxicillin; Anti-Bacterial Agents; Ceftriaxone; Cefuroxime; Cephalosporins; Clarithromycin; Humans; Microbial Sensitivity Tests; Penicillin Resistance; Pneumococcal Infections; Saudi Arabia; Streptococcus pneumoniae

The bactericidal activities of monotherapy with trovafloxacin (-0.37 +/- 0.15 Delta log(10) CFU/ml. h), vancomycin (-0.32 +/- 0.12 Delta log(10) CFU/ml. h), and ceftriaxone (-0.36 +/- 0.19 Delta log(10) CFU/ml. h) for the treatment of experimental meningitis in rabbits due to a clinical penicillin-resistant pneumococcal strain (MIC, 4 mg/liter) were similar. The combination of ceftriaxone with trovafloxacin considerably improved the killing rates (-0.67 +/- 0.16 Delta log(10) CFU/ml. h) and was slightly superior to ceftriaxone with vancomycin (killing rate, -0.53 +/- 0. 22 Delta log(10) CFU/ml. h), the regimen most commonly used in clinical practice. In vitro, synergy was demonstrated between ceftriaxone and trovafloxacin by the checkerboard method (fractional inhibitory concentration index, 0.5) and by time-killing assays over 8 h.

Topics: Animals; Anti-Infective Agents; Ceftriaxone; Cephalosporins; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Fluoroquinolones; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Naphthyridines; Penicillin Resistance; Pneumococcal Infections; Rabbits; Streptococcus pneumoniae

To determine whether reduced penicillin or ceftriaxone susceptibility affects clinical presentation and outcome in children with pneumococcal bacteremia.. Retrospective review of patients with Streptococcus pneumoniae bacteremia.. We reviewed 922 cases of pneumococcal bacteremia. Of 744 isolates with known penicillin (PCN) susceptibilities 56 were PCN-nonsusceptible. The majority displayed intermediate resistance; 14 of 730 isolates with known ceftriaxone (CTX) susceptibilities were CTX-nonsusceptible. Neither the PCN- nor the CTX-nonsusceptible cohort displayed a difference from its susceptible counterpart in temperature, respiratory rate or white blood cell count on initial patient evaluation, although trend suggested they were more often admitted at the initial visit. At follow-up only children treated initially with antibiotic were evaluated. Children with PCN-nonsusceptible isolates were no more likely to be febrile than those with PCN-susceptible isolates (28% vs. 25%, P = 0.61) and were no more likely to have a positive repeat blood culture (0% vs. 1%, P = 0.59) or a new focal infection (10% vs. 6%, P = 0.79). Data concerning CTX-nonsusceptible organisms were limited by the low number of such isolates. Although patients with CTX-nonsusceptible pneumococci were more likely to be febrile at follow-up than those with CTX-susceptible organisms (67% vs. 24%, P = 0.04), we were unable to demonstrate a significant difference for other endpoints.. Reduced antibiotic susceptibility does not alter the clinical presentation of pneumococcal bacteremia. With current practice intermediate resistance to PCN is of little clinical significance in nonmeningitic systemic pneumococcal infections.

Topics: Adolescent; Adult; Bacteremia; Ceftriaxone; Cephalosporin Resistance; Cephalosporins; Chi-Square Distribution; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Penicillin Resistance; Pneumococcal Infections; Retrospective Studies; Streptococcus pneumoniae; Treatment Outcome

In a context of worldwide emergence of resistance among Streptococcus pneumoniae strains, early detection of strains with decreased susceptibility to beta-lactam antibiotics is important for clinicians. If the 1-microgram oxacillin disk diffusion test is used as described by the National Committee for Clinical Laboratory Standards, no interpretation is available for strains showing zone sizes of /=2.0 microgram/ml) to penicillin. For ceftriaxone, among 98 strains with no zone of inhibition in response to oxacillin, 68 had intermediate resistance (MIC, 1.0 microgram/ml), and 22 were resistant (MIC, >/=2.0 microgram/ml). To optimize the use of the disk diffusion method, we propose that the absence of a zone of inhibition around the 1-microgram oxacillin disk be regarded as an indicator of nonsusceptibility to penicillin and ceftriaxone and recommend that such strains be reported as nonsusceptible to these antimicrobial agents, pending the results of a MIC quantitation method.

Topics: Ceftriaxone; Cephalosporin Resistance; Cephalosporins; Evaluation Studies as Topic; Humans; Microbial Sensitivity Tests; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae

Minimum inhibitory concentrations of penicillin, ceftriaxone, ciprofloxacin, and moxifloxacin (BAY 12-8039), a new 8-methoxyquinolone, were determined for 60 cerebrospinal fluid isolates of Streptococcus pneumoniae collected during January 1997-April 1998 at Italian medical centres. Three reference isolates with predetermined MIC values (two penicillin- and multidrug-resistant isolates, one uniformly susceptible to all antibiotics) were also tested with the same antibiotics. The MIC90 of penicillin was < or = 0.03 mg/L (range < or = 0.03-2 mg/L), of ceftriaxone 0.06 mg/L (range < or = 0.03-0.5 mg/L), of ciprofloxacin 2 mg/L (range 0.5-8 mg/L) and of moxifloxacin 0.06 mg/L (range 0.03-0.12 mg/L). Moxifloxacin was effective against all the penicillin-resistant isolates tested, with an MIC of 0.06 mg/L. Moxifloxacin was 32-fold more active than ciprofloxacin and was not affected by penicillin and cephalosporin resistance. These results indicate that moxifloxacin could be useful for the treatment of both penicillin-sensitive and -resistant S. pneumoniae meningitis.

Topics: Anti-Bacterial Agents; Aza Compounds; Ceftriaxone; Ciprofloxacin; Fluoroquinolones; Humans; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Moxifloxacin; Penicillins; Pneumococcal Infections; Quinolines; Streptococcus pneumoniae

In this study, disk diffusion testing with ceftizoxime and cefuroxime was evaluated for use in predicting the susceptibility of Streptococcus pneumoniae to ceftriaxone and cefotaxime. Of the 194 isolates included in this study, 138 were susceptible, 34 were intermediate, and 22 were resistant to cefotaxime by MIC testing; 138 isolates were susceptible, 35 were intermediate, and 21 were resistant to ceftriaxone by MIC testing. A zone of inhibition around the cefuroxime disk of >/=32 mm correctly categorized 101 of 138 isolates as susceptible to cefotaxime and ceftriaxone. A zone of inhibition around the ceftizoxime disk of >/=26 mm correctly categorized 111 of 138 isolates as susceptible to cefotaxime and 114 of 138 as susceptible to ceftriaxone. We conclude that disk diffusion can separate S. pneumoniae isolates susceptible to ceftriaxone and cefotaxime from those that are not susceptible. Isolates not falling into the susceptible category by disk diffusion require additional testing to determine the MIC.

Topics: Cefotaxime; Ceftizoxime; Ceftriaxone; Cefuroxime; Cephalosporin Resistance; Evaluation Studies as Topic; Humans; Microbial Sensitivity Tests; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae

Topics: Acute Kidney Injury; Adolescent; Arteriovenous Fistula; Ceftriaxone; Child; Cyclosporine; Female; Follow-Up Studies; Glomerulosclerosis, Focal Segmental; Humans; Kidney Transplantation; Male; Pneumococcal Infections; Postoperative Complications; Proteinuria; Surgical Wound Infection; Treatment Outcome

Topics: Acute Disease; Albuterol; Bacteremia; Bronchiolitis; Bronchodilator Agents; Ceftriaxone; Cephalosporins; Diagnosis, Differential; Humans; Infant; Male; Pneumococcal Infections

The activity of amoxycillin and ceftriaxone, alone and in combination, was tested against four strains of penicillin-resistant pneumococci in vitro and in an animal model. Three of the strains were also resistant to third-generation cephalosporins. Fractional inhibitory concentration indexes for combined amoxycillin and ceftriaxone were measured by the Etest method and were considered additive (1.2; 1.1; 1.3 and 1.3 for the four strains). Twenty-four hour time-kill curves for two strains showed that the combination was additive or synergic for concentrations up to the MIC of the single drugs. The efficacy of these antibiotics alone and in various combinations against strains 16089 and 11724 were investigated in vivo using prolonged (48 h) experimental fibrin clot infection in rabbits. The bacterial reductions (delta log10 cfu/g) obtained for all the antibiotic combinations tested were significantly higher than those of the single drug regimens. The in-vivo efficacy of amoxycillin was significantly correlated with the time for which its concentration was above the MIC and that of ceftriaxone was correlated with its maximal concentration. From these findings, we concluded that, at concentrations easily achievable in humans, the combination of amoxycillin and ceftriaxone was strongly synergic against infection due to penicillin- and cephalosporin-resistant pneumococci.

Topics: Amoxicillin; Animals; Ceftriaxone; Cephalosporins; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Drug Therapy, Combination; Male; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Pneumococcal Infections; Rabbits; Streptococcus pneumoniae; Time Factors

The emergence of antibiotic resistance in Streptococcus pneumoniae poses a particular threat to HIV-infected patients. These patients are at increased risk of invasive pneumococcal disease and may respond poorly to pneumococcal vaccination. We describe an HIV-infected patient with recurrent aortic valve endocarditis due to the same serotype of S. pneumoniae (19A) despite appropriate treatment with penicillin and immunoprophylaxis. The pneumococcus responsible for the second episode of endocarditis was susceptible to cefotaxime (MIC of 0.06 microg/ml), but was no longer susceptible to penicillin (MIC of 0.25 microg/ml). The patient was treated successfully with 4 weeks of intravenous ceftriaxone.

Topics: Aortic Valve; Bacterial Vaccines; Ceftriaxone; Echocardiography; Endocarditis, Bacterial; Heart Valve Diseases; HIV Infections; Humans; Male; Middle Aged; Penicillin G; Penicillin Resistance; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Recurrence; Streptococcus pneumoniae

MICs of 21 beta-lactams were determined by agar dilution against 283 penicillin-susceptible (pen-S), 122 intermediate (pen-I) and 23 fully penicillin-resistant (pen-R) pneumococci. MICs of all beta-lactams increased with increasing MICs of penicillin. Clometocillin was the most active penicillin against pen-I or pen-R pneumococci. All oral cephalosporins except cefuroxime and cefpodoxime were less active than penicillin and none was satisfactory against pen-I or pen-R pneumococci. The parenteral third- and fourth-generation cephalosporins (except ceftazidime) were similar in activity to penicillin against pen-S isolates. Cefpirome showed the lowest mean MICs against pen-I and pen-R strains.

Topics: Amoxicillin; Ampicillin; Anti-Bacterial Agents; beta-Lactams; Carbapenems; Cefaclor; Cefadroxil; Cefatrizine; Cefepime; Cefixime; Cefotaxime; Cefpirome; Cefpodoxime; Ceftazidime; Ceftibuten; Ceftizoxime; Ceftriaxone; Cefuroxime; Cephalosporins; Cephradine; Drug Resistance, Microbial; Drug Resistance, Multiple; Humans; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Piperacillin; Pneumococcal Infections; Serotyping; Species Specificity; Streptococcus pneumoniae

One hundred six cases of invasive pneumococcal infections diagnosed from 1985 to 1996 were analyzed retrospectively. The types of infection were bacteremia without focus (45%), meningitis (19%), peritonitis (17%), pneumonia (bacteremic) (16%), and others (3%). Penicillin-nonsusceptible Streptococcus pneumoniae was first detected in 1989, and its incidence increased rapidly thereafter, reaching 89% in 1995. Initial empirical regimens were of parenteral beta-lactam antimicrobials with or without an aminoglycoside, but these were modified subsequently. Among the 72 nonmeningeal infections analyzed, a favorable response at 72 hours and death were observed in 83% and 2.5%, respectively, of 40 penicillin-susceptible infections, as compared with 86% (P = 1.0) and 7.1% (P = .45) of 14 infections due to intermediate strains and 61% (P = .07) and 11% (P = .22) of 18 due to resistant strains. The favorable-response rate and mortality among 49 patients not in initially critical condition were 92% and zero, respectively, as compared with 52% (P = .00027) and 17% (P = .008) of 23 in critical condition. The data suggest that clinical outcome of penicillin-nonsusceptible pneumococcal infection outside the CNS may be more closely related to clinical condition at presentation than to the level of resistance of the causative strain when such infection is treated with parenteral beta-lactams.

Topics: Adolescent; Cefotaxime; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Female; Humans; Infant; Korea; Male; Microbial Sensitivity Tests; Penicillin G; Penicillin Resistance; Penicillins; Pneumococcal Infections; Retrospective Studies; Streptococcus pneumoniae; Vancomycin

To assess the clinical outcome and risk of failure after oral vs. intravenous treatment in otitis media caused by penicillin-resistant pneumococci. To determine the possible correlations between pneumococcal minimal inhibitory concentration (MIC) to penicillin and clinical outcome.. Retrospective study of 156 cases collected between 1993 and 1995. Mean follow-up: 5 months. Setting. Two tertiary academic medical centers in Paris, France.. Pneumococcus was isolated from 191 of 570 ear samples obtained from children with otitis media and shown to be penicillin-resistant in 156. Medical history, antibiotic therapy during the previous 3 months and day-care center attendance were reviewed. For the current episode microbiologic characteristics of the isolated strains, type of treatment, therapy efficacy and clinical outcome were analyzed. Patients were predominantly young (76.3% were <1 year old) and bacteriologic samples were taken mainly because of previous treatment failure.. Among 156 children with pneumococcal penicillin-resistant otitis media, 72.2% attended day-care centers, 71.8% had been previously treated with aminopenicillin and 52.5% with cephalosporins. Failure of previous empirical oral therapy was noted in 84% (one-third of these had been receiving amoxicillin-clavulanate). Patients treated intravenously had had a more protracted otitis but no greater number of previous episodes of acute otitis media than those receiving oral therapy. Acute mastoiditis occurred in 4 infants resulting in mastoidectomy. Oral treatment (mainly with high dose amoxicillin,120 to 150 mg/kg/day) and intravenous therapy (cephalosporin or glycopeptide) had been used in 59 and 41%, respectively. Mean duration of therapy was 10.7 days. Three failures (1.9%) and 10 recurrences (6.4%, average 28 days) occurred. No statistical difference was found between intravenous and oral therapy with respect to risk of recurrence. A high penicillin MIC value was correlated with previous antibiotic treatment but not with clinical outcome.. Oral therapy appears to be as effective as intravenous therapy for the treatment of penicillin-resistant pneumococcal otitis media. Intravenous treatment should not necessarily be dictated by the penicillin susceptibility value but should be considered in cases of failure to thrive, persistent otitis or other complications.

Topics: Acute Disease; Administration, Oral; Amoxicillin; Cefotaxime; Ceftriaxone; Cephalosporins; Humans; Infant; Injections, Intravenous; Microbial Sensitivity Tests; Otitis Media; Penicillin Resistance; Penicillins; Pneumococcal Infections; Retrospective Studies; Streptococcus pneumoniae; Treatment Failure

To track antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from children with systemic infections and determine outcome of treatment.. A 3-year (September 1993 through August 1996) prospective surveillance study of all invasive pneumococcal infections in children.. Infants and children cared for at eight children's hospitals in the United States with culture-proven systemic pneumococcal infection.. One thousand two hundred ninety-one episodes of systemic pneumococcal infection were identified in 1255 children. An underlying illness was present in the children for 27% of the episodes. The proportion of isolates that were nonsusceptible to penicillin or ceftriaxone increased annually and nearly doubled throughout the 3-year period; for the last year the percentages of isolates nonsusceptible to penicillin and ceftriaxone were 21% and 9.3%, respectively. There was no difference in mortality between patients with penicillin-susceptible or nonsusceptible isolates. Only 1 of 742 patients with bacteremia had a repeat blood culture that was positive > 1 day after therapy was started. All 24 normal children with bacteremia attributable to isolates resistant to penicillin had resolution of their infection; the most common treatment regimen was a single dose of ceftriaxone followed by an oral antibiotic.. The percentage of pneumococcal isolates nonsusceptible to penicillin and ceftriaxone increased yearly among strains recovered from children with systemic infection. Because empiric antibiotic therapy already has changed for suspected pneumococcal infections, antibiotic resistance has not been associated with increased mortality. Careful monitoring of antibiotic susceptibility and outcome of therapy is necessary to continually reassess current recommendations for treatment.

Topics: Adolescent; Bacteremia; Ceftriaxone; Child; Child, Preschool; Drug Resistance, Microbial; Humans; Infant; Penicillins; Pneumococcal Infections; Population Surveillance; Prospective Studies; Risk Factors; Serotyping; Streptococcus pneumoniae; Treatment Outcome; United States

Previous studies have suggested that penicillin-resistant pneumococcal isolates (especially those with MIC > 1 microgram/mL) usually are clonally related. To test this hypothesis, the molecular epidemiology of 29 clinical isolates of penicillin-resistant pneumococci (of which 83% were also resistant to either cefotaxime or ceftriaxone) collected in central Taiwan was investigated by pulsed field gel electrophoresis. Twenty-seven distinct patterns were identified. Our results indicate that an increase in penicillin-resistant S. pneumoniae between April 1993 and June 1994 in central Taiwan is not due to the clonal dissemination of a limited number of epidemic strains.

Topics: Cefotaxime; Ceftriaxone; Cephalosporin Resistance; Drug Resistance, Multiple; Electrophoresis, Gel, Pulsed-Field; Humans; Microbial Sensitivity Tests; Molecular Epidemiology; Oxacillin; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae; Taiwan

Topics: Adult; Amoxicillin; Ceftriaxone; Cephalosporins; Female; Follow-Up Studies; Humans; Penicillins; Peritonitis; Pneumococcal Infections; Salpingitis; Time Factors; Tomography, X-Ray Computed

We conducted a survey to assess the prevalence and geographic distribution of antimicrobial drug resistance among invasive isolates of Streptococcus pneumoniae in Washington State. Sequential sterile-site pneumococcal isolates were submitted from 13 hospital laboratories between 1 October 1995 and 30 January 1997. We serotyped 275 isolates from adults and children and determined minimum inhibitory concentrations (MIC) for commonly used antimicrobial drugs. Data were abstracted from medical records to compare differences in outcome and risk factors for infection. Of the 275 isolates, 73 (26.5%) were nonsusceptible to one or more antimicrobial drugs. Penicillin-nonsusceptible pneumococci (PNSP, MIC > or = 0.1 microgram/ml) accounted for 42 (15.3%) of the 275 isolates including 4 (1.5%) resistant strains (MIC > or = 2 micrograms/ml). The 42 PNSP included serogroups 6, 9, 14, 19, and 23, all of which are represented in the 23-valent pneumococcal vaccine. PNSP were also nonsusceptible to trimethoprim/sulfamethoxazole (92.9%), erythromycin (38.1%), imipenem (28.6%), and ceftriaxone (23.8%). Forty-seven (17.1%) of the 275 isolates were multiple drug-nonsusceptible pneumococci (MDNSP). A significantly greater number of patients < or = 12 years of age were infected with MDNSP compared with those > 12 years. Prior use of antimicrobial drugs and an immunosuppressive disorder were risk factors for infection with PNSP. In summary, pneumococci nonsusceptible to penicillin and other antimicrobial drugs are prevalent among adults with invasive pneumococcal disease in Washington State. A large proportion of PNSP are resistant to other commonly used antimicrobial drugs. Local antibiotic susceptibility data should be considered when designing empiric treatment regimens.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ceftriaxone; Cephalosporin Resistance; Cephalosporins; Child; Child, Preschool; Drug Resistance, Microbial; Erythromycin; Female; Humans; Imipenem; Infant; Male; Middle Aged; Penicillin Resistance; Pneumococcal Infections; Prevalence; Risk Factors; Serotyping; Streptococcus pneumoniae; Thienamycins; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Washington

To assess the prevalence of antibiotic resistance and serotype distribution among pneumococci in England and Wales in 1990 and 1995.. Observational surveys in March 1990 and March 1995. During two weeks in each survey period all pneumococci isolated in public health laboratories in England and Wales were collected and assessed for sensitivity to antibiotics and the distribution of serogroups or serotypes.. The network of public health laboratories throughout England and Wales.. 1127 individual patient isolates of Streptococcus pneumoniae obtained during the two surveys.. Sensitivity or resistance to a range of antibiotics; serogroup or serotype.. The prevalence of intermediate or full resistance to penicillin increased from 1.5% in 1990 to 3.9% in 1995 and resistance to erythromycin increased from 2.8% to 8.6%. About 92% of isolates belonged to serogroups or serotypes included in the currently available pneumococcal vaccine.. Resistance to penicillin and erythromycin has increased among pneumococci in England and Wales. Continued surveillance to assess further increases in the prevalence of pneumococcal resistance to antibiotics is essential.

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Drug Resistance, Microbial; England; Erythromycin; Humans; Penicillin Resistance; Pneumococcal Infections; Prevalence; Prospective Studies; Rifampin; Serotyping; Streptococcus pneumoniae; Vancomycin; Wales

The prevalence of resistant Streptococcus pneumoniae (SP) is increasing world-wide. Pneumococcal prevalence and susceptibility patterns are not known for children in the Top End of the Northern Territory.. To determine the prevalence of nasopharyngeal carriage of pneumococci in children hospitalised in Darwin, and the extent of penicillin and ceftriaxone resistance in these isolates.. Nasopharyngeal swabs were collected on admission from 85 children who had not received antimicrobials for their admission illness. Antimicrobial resistance was determined following selective culture for SP isolates. Minimal inhibitory concentrations (MICs) for penicillin and ceftriaxone were determined using the E-test method.. The overall prevalence of nasopharyngeal SP carriage was 44%. Carriage occurred more often in Aboriginal children from rural areas (56%) than in urban children (24%) (OR 3.94, 95% CI 1.35-11.78, p < 0.01). Thirty per cent of isolates were penicillin resistant, 35% were ceftriaxone resistant, and 49% were resistant to at least one of these. One isolate showed high-level resistance to both antimicrobials; all other resistant isolates were of intermediate-level resistance. For the same isolate, MICs for ceftriaxone were more often higher than those for penicillin. Five isolates had intermediate resistance to ceftriaxone whilst remaining sensitive to penicillin.. The prevalence of pneumococcal resistance to penicillin and ceftriaxone in hospitalised children in Darwin is much higher than previously reported in Australia. This has implications for future antimicrobial management and highlights the need for regular regional surveillance of SP resistance. The development of conjugate pneumococcal vaccines for children under two years is a priority.

Topics: Ceftriaxone; Cephalosporin Resistance; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Nasopharynx; Native Hawaiian or Other Pacific Islander; Northern Territory; Penicillin Resistance; Pneumococcal Infections; Prevalence; Streptococcus pneumoniae

We used a gerbil model of otitis media to assess the efficacy of single-dose ceftriaxone against three Streptococcus pneumoniae strains highly resistant to penicillin (MICs, 4 to 8 micrograms/ml) and with various susceptibilities to ceftriaxone (MICs, 0.5, 4, and 8 micrograms/ml). Middle ear infection was induced by bilateral transbullar challenge with 10(7) bacteria per ear. Antibiotic treatment was administered subcutaneously at 2 h postinfection. Infection status was checked 2 days later by counting the bacteria in middle ear and cerebrospinal fluid samples. With the cefriaxone-susceptible strain (MIC, 0.5 microgram/ml), we tested doses of 5 to 100 mg/kg of body weight. With a dose of 50 mg/kg, treatment outcome was equivalent to that with amoxicillin, which was used as a reference (25 mg/kg, two injections); no bacteria were recovered from 82% of the middle ear samples, and the rate of cerebrospinal fluid culture positivity was significantly reduced to 6%, relative to 59% for the untreated controls. Similar efficacy was obtained with a dose of 100 mg/kg against the two ceftriaxone-resistant strains. Pharmacokinetic study indicates that the values of the parameters in plasma after the administration of a dose of 100 mg/kg (peak level of total drug, 268 +/- 33 micrograms/ml; elimination half-life, 0.8 h; area under concentration-time curve, 488 micrograms.h.ml-1) were still suboptimal compared with the values of the parameters measured in pediatric patients after intravenous or intramuscular administration of a dose of 50 mg/kg. Our results indicate the efficacy of ceftriaxone against experimental cephalosporin-resistant pneumococcal otitis and provide a basis for the clinical use of single-dose ceftriaxone against pneumococcal otitis media.

Topics: Animals; Ceftriaxone; Cephalosporin Resistance; Cephalosporins; Chromatography, High Pressure Liquid; Female; Gerbillinae; Half-Life; Microbial Sensitivity Tests; Otitis Media; Penicillin Resistance; Pneumococcal Infections; Streptococcus pneumoniae

We investigated the combination of teicoplanin and ceftriaxone for its bactericidal activity against Staphylococcus aureus, Haemophilus influenzae type b and Streptococcus pneumoniae isolated from bone and joint infections in children. An increase in bactericidal activity was observed against isolates of S. aureus and H. influenzae when the antibiotics were tested at fractional MICs whereas indifference was observed at their MICs. Similar results were obtained at fractional MICs against S.pneumoniae, but the bactericidal activity fell by more than 1 x log 10 cfu/mL when the antibiotics were tested at or above their MICs.

Topics: Bacterial Infections; Bone Diseases; Ceftriaxone; Child, Preschool; Drug Interactions; Drug Resistance, Microbial; Drug Therapy, Combination; Haemophilus Infections; Humans; Infant; Joint Diseases; Microbial Sensitivity Tests; Penicillin G; Pneumococcal Infections; Staphylococcal Infections; Teicoplanin

Topics: Adult; Age Factors; Amoxicillin; Cefotaxime; Ceftriaxone; Cephalosporins; Child, Preschool; Humans; Incidence; Infant; Infant, Newborn; Penicillin Resistance; Penicillins; Pneumococcal Infections; Risk Factors; Streptococcus pneumoniae

Meropenem and comparator antibiotics, including ceftriaxone, ceftazidime, benzyl penicillin and a combination of ampicillin plus gentamicin, were evaluated in a model of bacterial meningitis in the guinea-pig. The model is an acute infection in which challenge with each organism, if untreated, causes an increase in numbers of white blood cells, elevation of protein concentrations and 6-8 log10 cfu/mL of bacteria in the CSF. Infections caused by Haemophilus influenzae, Neisseria meningitidis, three strains of Streptococcus pneumoniae (two penicillin-resistant), Escherichia coli, Pseudomonas aeruginosa and Listeria monocytogenes all responded to meropenem, which was as active as the comparator agents in all studies, and was more active in most. Of particular note were the results seen against S. pneumoniae (penicillin-resistant) infections, in which meropenem was significantly more effective than ceftriaxone. Also notable were results from the P. aeruginosa infection where meropenem, at low doses, was more effective than ceftazidime. Activity against L. monocytogenes was equivalent to that produced by treatment with the combination of ampicillin plus gentamicin, even when treatment was delayed. These results show that, in an animal model, meropenem penetrates into CSF in concentrations sufficient to produce significant reductions in the numbers of common and less common pathogens.

Topics: Ampicillin; Animals; Carbapenems; Ceftazidime; Ceftriaxone; Cephalosporins; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Drug Evaluation; Drug Resistance, Microbial; Escherichia coli Infections; Gentamicins; Guinea Pigs; Haemophilus Infections; Haemophilus influenzae; Listeriosis; Meningitis, Bacterial; Meropenem; Neisseria meningitidis; Penicillin G; Pneumococcal Infections; Thienamycins

Adding rifampin to penicillin or l-ofloxacin diminished the rate at which these antibiotics killed 21 clinical isolates isolates of Streptococcus pneumoniae in vitro. A less pronounced inhibitory effect was observed when rifampin was added to ceftriaxone. Synergy was not observed for any bacterial isolate. The in vitro demonstration of indifference or antagonism using these antibiotic combinations argues against the empirical addition of rifampin to beta-lactams or fluoroquinolones in treating serious pneumococcal infections.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; Cephalosporins; Colony Count, Microbial; Humans; Microbial Sensitivity Tests; Ofloxacin; Penicillin G; Pneumococcal Infections; Rifampin; Streptococcus pneumoniae

The increasing emergence of penicillin-resistant (Pr) strains of Streptococcus pneumoniae could pose a therapeutic problem in the next few years. Ceftriaxone (CRO), a broad-spectrum cephalosporin, exhibits a smaller increase in MICs against Pr S. pneumoniae strains than amoxicillin (AMO) (usually referred as to the "gold standard" therapy for pneumococcal infections). Therefore, we compared their respective efficacies in a leukopenic Swiss mouse model of pneumococcal pneumonia. Infection was induced with two serotype 19 strains: a penicillin-susceptible (Ps) strain (MICs of < 0.01 for penicillin, 0.03 for AMO, and 0.03 for CRO) and a Pr strain (MICs of 4 for penicillin, 2 for AMO, and 0.5 for CRO). Untreated mice died within 2 or 3 days. Against the Ps strain, the minimal protective dose (two subcutaneous injections at 12-h intervals for 3 days) for both CRO and AMO was 5 mg/kg of body weight (87% survivors). Ten-fold-increased doses of CRO (50 mg/kg) gave similar protection (75% survivors) against the Pr strain, whereas 20- and 40-fold-increased doses of AMO protected 0 and 34% of the animals, respectively, against the Ps strain. CRO had a marked and prolonged antibacterial effect in the lungs (2.7-log-unit reduction of CFU in 24 h after a single 50-mg/kg injection) against the Pr strain in comparison with AMO. A standard dosage of 50 mg of CRO per kg in mice resulted in peak levels in serum and protein binding comparable to those observed with 1 g given intravenously in humans. This dosage remained effective against a highly Pr S. pneumoniae strain in this model. The microbiological activity and pharmacodynamic and pharmacokinetic properties of CRO (time during which concentrations exceed the MIC for the test pathogen [delta t MIC], > or less than 8 h; and peak/MIC ratio, >90 for free active drug) accounted for its efficacy relative to AMO (50 mg/kg: delta t MIC, <2; peak/MIC ratio, <25) against the highly Pr S. pneumoniae strain used in this study.

Topics: Amoxicillin; Animals; Ceftriaxone; Disease Models, Animal; Female; Injections, Subcutaneous; Lung; Mice; Microbial Sensitivity Tests; Penicillin Resistance; Pneumococcal Infections; Pneumonia, Pneumococcal; Streptococcus pneumoniae

Topics: Ceftriaxone; Child; Dacryocystorhinostomy; Dexamethasone; Female; Humans; Meningitis, Bacterial; Pneumococcal Infections

The in vitro activity of cefodizime and two comparative cephalosporins, cefuroxime and ceftriaxone were studied against respiratory pathogens. MIC90s of cefodizime were 0.06-0.512 microgram/ml for Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae. MIC50s of cefodizime for Klebsiella pneumoniae and Staphylococcus aureus isolates were 2 micrograms/ml and 8 micrograms/ml respectively. Cefuroxime and ceftriaxone at a concentration of 2 micrograms/ml and 1 microgram/ml inhibited 50% of Klebsiella pneumoniae and 50% of Staphylococcus aureus strains studied respectively. Cefodizime inhibited many of the important respiratory pathogens and can be suggested as an active antimicrobial agent for respiratory tract infections.

Topics: Cefotaxime; Ceftriaxone; Cefuroxime; Haemophilus Infections; Haemophilus influenzae; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus aureus; Streptococcus pneumoniae

Topics: Aged; Ceftriaxone; Female; Humans; Lumbar Vertebrae; Osteomyelitis; Penicillin Resistance; Pneumococcal Infections; Spondylitis; Streptococcus pneumoniae

In a mouse model using intraperitoneal inoculation of Streptococcus pneumoniae type 3, the 50% effective dose, ED50, after single doses one hour post-inoculation was considerably lower for ceftriaxone (CRO) than for cefuroxime (CXM) and cefotaxime (CTX), in spite of the same minimal inhibitory concentration, MIC, of 0.02 mcg/ml against the pneumococcus for all 3 drugs. The bactericidal activity as measured by time-kill curves was similar for the 3 drugs, as was the post-antibiotic effect in vitro. Protein binding in mouse serum was considerably higher for CRO (87%) than for both CTX (35%) and CXM (15%), respectively. Of pharmacokinetic parameters investigated on doses equal to the ED50s, the time the serum antibiotic concentration remained above the MIC (delta T(MIC)) was the factor that varied the least among 3 drugs. Therefore, the superior in vivo effect for CRO is not due to higher intrinsic activity against the pathogen but to the long serum-elimination half-life resulting in an extended delta T(MIC), probably related to the high serum protein binding.

Topics: Animals; Cefotaxime; Ceftriaxone; Cefuroxime; Cephalosporins; Female; Mice; Microbial Sensitivity Tests; Pneumococcal Infections; Protein Binding; Streptococcus pneumoniae

A 75-year-old man developed acute transient agranulocytosis. Hematologic data and course were suggestive of a toxic etiology. The patient had been admitted for pneumococcal septicemia and a polymicrobial abscess of the soft tissues of the left leg. At the time of diagnosis of the agranulocytosis, he had received 36 g ceftriaxone. The agranulocytosis resolved following discontinuation of ceftriaxone. This drug was, in all likeliness, responsible for the hematologic disorder. Renal failure occurred concomitantly with the agranulocytosis. Other similar cases have been reported. In view of these data, blood counts should be monitored in patients receiving prolonged courses of ceftriaxone.

Topics: Abscess; Acute Kidney Injury; Aged; Agranulocytosis; Ceftriaxone; Humans; Long-Term Care; Male; Pneumococcal Infections; Sepsis