cefotaxime and Pneumonia--Pneumococcal

We report the case of a patient who presented with RM associated with bacteremic pneumococcal pneumonia and review the literature on this condition.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefotaxime; Ceftazidime; Female; Humans; Pneumonia, Pneumococcal; Rhabdomyolysis; Streptococcus pneumoniae

Single drug therapy using a third generation cephalosporin of the cefotaxime type is possible in a number of situations where host defenses are intact, the causative microorganism is very sensitive (MIC less than 1 mg/l) and not concerned with phenomena of resistance by mutation, and the antibiotic is able to reach the site of infection at high concentrations. In contrast, the indications for two-drug therapy including an aminoglycoside appear to be better identified in patients with granulocytopenia. The possibility of single drug therapy preceded by a short period of two-drug therapy is also discussed.

Topics: Bacteria; Cefotaxime; Drug Therapy, Combination; Gonorrhea; Humans; Meningitis; Pneumonia, Pneumococcal; Urinary Tract Infections

This study compared the efficacy and tolerability of once-daily dosing with either roxithromycin or cefixime in previously healthy adult patients aged between 18 and 60 with markers of uncomplicated community-acquired pneumonia (CAP) in three outpatient clinics in an open, randomized study. Sixty patients were enrolled: 17 males and 13 females received roxithromycin 300 mg once daily for 8-10 days and 22 males and eight females received 400 mg cefixime once daily for the same period. All patients were assessed clinically, radiologically and bacteriologically before inclusion, immediately after the study and approximately 1 month later. The most common pathogen isolated from sputum was Streptococcus pneumoniae (in 26 (43%) of 60 patients), with mixed organisms isolated from the sputum of 18 (30%) of 60 patients. Staphylococcus aureus, Haemophilus influenzae or Moraxella catarrhalis occurred in 11/60 patients, and atypical pathogens were detected by serology in 7/26 cases in the roxithromycin group and 3/23 in the cefixime group. The severity of infection was rated as mild to moderate at the beginning of the trial. At the end of the study treatment period, clinical cure rates were 30/30 (100%) for roxithromycin and 28/30 (94%) for cefixime, with one patient on cefixime being classed as a partial responder and one patient being classed as a failure and withdrawn. However, radiological abnormalities persisted in three patients on roxithromycin and one on cefixime. Of the 59 patients who completed the study, none required further antibiotic therapy. No abnormal laboratory parameters or adverse events were reported in either group. Roxithromycin at a daily dose of 300 mg was an effective and well-tolerated treatment for the empirical treatment of mild to moderate CAP in this group of patients.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Cefixime; Cefotaxime; Cephalosporins; Community-Acquired Infections; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Roxithromycin; Streptococcus pneumoniae

Preliminary results have recently shown that an early switch from parenteral antimicrobials to an oral substitute provides an effective means of treating pneumonia in pediatric patients. In a controlled randomized study, 62 children with community-acquired lobar/segmental pneumonia were selected to receive 8 days of cefixime or amoxicillin-clavulanate after an initial therapy of two doses of parenteral ceftriaxone. Enrollment criteria included: age 6 months to 5 years, fever > 38.5 degrees C, white blood cell (WBC) count > or = 15,000/ mm3, and lobar/segmental pneumonia on chest radiograph. Twenty-nine patients were randomized to receive oral cefixime and 33 to oral amoxicillin-clavulanate. The two groups were comparable in the following pretreatment parameters: age, duration of illness, temperature, mean WBC count, erythrocyte sedimentation rate, C-reactive protein, and need for hospitalization. Days of resolution of high fever, tachypnea, cough, grunting, and laboratory test abnormalities were similar in the two groups. Clinical response at the end of treatment showed cure, improvement, and failure in 97%, 3%, and 0%, respectively, in the cefixime group and in 88%, 6%, and 6%, respectively in the amoxicillin-clavulanate group (P = NS). We conclude that young children with community-acquired lobar/segmental pneumonia can be successfully treated with 2 days of parenteral ceftriaxone followed by 8 days of oral cefixime or amoxicillin-clavulanate.

Topics: Administration, Oral; Amoxicillin; Cefixime; Cefotaxime; Ceftriaxone; Cephalosporins; Child, Preschool; Clavulanic Acids; Drug Therapy, Combination; Female; Humans; Infant; Male; Penicillins; Pneumonia, Pneumococcal; Radiography

In a prospective, open clinical trial 21 patients suffering from lower respiratory tract infections were treated with the new oral cephalosporin cefixime. The antibiotic was given at a dosage of 200 mg b. i. d. for seven to eleven days. Seventeen of 18 evaluable patients were cured or distinctly improved at the end of therapy as well as two days after the end of treatment. Clinical results correlated well with the results of the lung function tests, especially with the significant decrease of resistance. At the end of therapy all initially isolated pathogens were eradicated. The tolerability of cefixime was good, only in two patients treated mild and transient side effects were noticed (1 x diarrhea, 1 x epigastric pain).

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Bronchitis; Bronchopneumonia; Cefixime; Cefotaxime; Citrobacter; Drug Resistance, Microbial; Drug Tolerance; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Haemophilus Infections; Humans; Male; Middle Aged; Pneumonia; Pneumonia, Pneumococcal; Prospective Studies; Proteus Infections

A clinical trial was designed to evaluate the efficacy and safety of cefotaxime, a new semisynthetic, broad-spectrum cephalosporin, in the therapy of community-and hospital-acquired pneumonias. Thirty-nine males (mean age, 65 years) were treated for 41 episodes of pneumonia. Only five patient did not have a serious underlying disease; 15 had two or more significant disorders. Sixty-six percent of these pneumonias were due to Streptococcus pneumoniae or Haemophilus influenzae. The minimal inhibitory concentrations for all bacterial isolates ranged from 0.008 to 4 micrograms/ml. Peak serum cefotaxime levels during therapy ranged from 12 to 124 micrograms/ml 1 h after a 1-g dose. Satisfactory bacteriological and clinical responses were observed in 85% of the cases. Four episodes of pulmonary superinfections due to cefotaxime-resistant gram-negative bacilli were noted, each in a patient being mechanically ventilated. Pseudomonas was involved in each of these superinfections, and three were fatal. No serious toxicity or adverse reaction to cefotaxime was seen. The results of this study suggest that cefotaxime is an affective and well-tolerated new cephalosporin antimicrobial agent for the therapy of pneumonia due to susceptible organisms.

Topics: Adolescent; Adult; Aged; Cefotaxime; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Haemophilus Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Pneumonia, Pneumococcal; Pseudomonas Infections; Random Allocation

Topics: Adolescent; Adult; Aged; Cefotaxime; Cephalosporins; Child; Female; Humans; Male; Middle Aged; Penicillins; Pneumonia, Pneumococcal; Streptococcus pneumoniae

Oral beta-lactam antimicrobials are not routinely tested against Streptococcus pneumoniae due to presumed susceptibility based upon penicillin minimum inhibitory concentration (MIC) testing. Currently, Clinical and Laboratory Standards Institute provides comments to use penicillin MIC ≤0.06 to predict oral cephalosporin susceptibility. However, no guidance is provided when cefotaxime MIC is known, leading to uncertainty with interpretation. The purpose of this study was to evaluate cefotaxime and penicillin MICs and their respective correlation to oral beta-lactam categorical susceptibility patterns.. 249 S. pneumoniae isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-ToF) and then tested by broth microdilution method to penicillin, cefotaxime, amoxicillin, cefdinir, cefpodoxime, and cefuroxime.. Using Clinical and Laboratory Standards Institute (CLSI) non-meningitis breakpoints for cefotaxime, 240/249 isolates were classified as susceptible. Of the cefotaxime susceptible isolates, 23% of the isolates are misrepresented as cefdinir susceptible. Amoxicillin correlated well with penicillin MIC breakpoints with only 1 discordant isolate out of 249.. The correlation between amoxicillin and penicillin creates a very reliable predictor to determine categorical susceptibility. However oral cephalosporins were not well predicted by either penicillin or cefotaxime leading to the possible risk of treatment failures. Caution should be used when transitioning to oral cephalosporins in cefotaxime susceptible isolates, especially with higher cefotaxime MICs.

Topics: Administration, Oral; Amoxicillin; Anti-Bacterial Agents; beta-Lactams; Cefotaxime; Cephalosporins; Humans; Microbial Sensitivity Tests; Penicillins; Pneumonia, Pneumococcal; Streptococcus pneumoniae

To investigate drug resistance features and homology among penicillin-intermediate. Fifty-one penicillin-intermediate. Transmission of penicillin-intermediate

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Child, Preschool; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Molecular Typing; Penicillin Resistance; Penicillins; Pneumonia, Pneumococcal; Polymerase Chain Reaction; Retrospective Studies; Sequence Homology, Nucleic Acid; Streptococcus pneumoniae; Vancomycin

Topics: Amoxicillin; Anti-Bacterial Agents; beta-Lactams; Cefotaxime; Drug Industry; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Penicillins; Pneumonia, Pneumococcal; Politics; Practice Guidelines as Topic; Streptococcus pneumoniae; Terminology as Topic

Group B Streptococcus is a primary source of pneumonia, which is a leading cause of death worldwide. During the last few decades, there has been news of growing antibiotic resistance in group B streptococci to penicillin and different antibiotic agents. This clinical study retrospectively analyzes antimicrobial resistance in inpatients who were diagnosed with group B streptococcal pneumonia.. All of the required information from inpatients who were identified to have group B streptococcal pneumonia was sourced from the database at the Department of Internal Medicine of HELIOS Clinic Wuppertal, Witten/Herdecke University, in Germany, from 2004-2014. Antimicrobial susceptibility testing was performed for the different antimicrobial agents that were regularly administered to these inpatients.. Sixty-six inpatients with a mean age of 63.3 ± 16.1 years (45 males [68.2%, 95% CI 60.0%-79.4%] and 21 females [31.8%, 95% CI 20.6%-43.0%]) were detected to have group B streptococcal pneumonia within the study period from January 1, 2004, to August 12, 2014. Group B Streptococcus had a high resistance rate to gentamicin (12.1%), erythromycin (12.1%), clindamycin (9.1%), and co-trimoxazole (3.0%), but it was not resistant to penicillin, cefuroxime, cefotaxime, or vancomycin (P < 0.0001).. No resistance to penicillin, cefuroxime, cefotaxime, or vancomycin was detected among inpatients with pneumonia caused by group B streptococci.

Topics: Aged; Cefotaxime; Cefuroxime; Cephalosporin Resistance; Cross Infection; Drug Resistance, Bacterial; Female; Germany; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Penicillin Resistance; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Retrospective Studies; Streptococcal Infections; Streptococcus agalactiae; Vancomycin Resistance

Topics: Ampicillin; Anti-Bacterial Agents; Bacteremia; Cefotaxime; Female; Gentamicins; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pneumococcal Infections; Pneumonia, Pneumococcal; Spain; Streptococcus pneumoniae; Vagina

Few studies have assessed the clinical characteristics and outcomes of invasive pneumococcal diseases in cirrhotic patients. We reviewed the medical records of adult cirrhotic patients with pneumococcal bacteremia from January 1997 to April 2006. During this time, 62 episodes of pneumococcal bacteremia occurred in 59 patients with liver cirrhosis, 45 (76.3%) of whom were classified as Child-Pugh grade C. The most common source of infection was spontaneous bacterial peritonitis (SBP) (45.8%), followed by primary bacteremia (40.7%) and pneumonia (10.1%). The 30-day mortality rate was 16.9%, with all fatalities in patients classified as Child-Pugh grade C. The median model for end-stage liver disease score of patients who died was significantly higher than that of survivors (26.5 versus 17.0, P=0.001). Pneumococcal bacteremia in adult cirrhotic patients was more commonly associated with SBP than with pneumonia. Most cases of bacteremia and fatal outcomes occurred in patients with advanced cirrhosis.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cefotaxime; Female; Humans; Liver Cirrhosis; Male; Microbial Sensitivity Tests; Middle Aged; Peritonitis; Pneumococcal Infections; Pneumonia, Pneumococcal; Statistics, Nonparametric

Topics: Cefotaxime; Combined Modality Therapy; Debridement; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Fever; Foot; Gangrene; Hand; Humans; IgA Vasculitis; Immunocompetence; Infant; Ischemia; Male; Physical Therapy Modalities; Plasma; Plastic Surgery Procedures; Pneumococcal Infections; Pneumonia, Pneumococcal; Sepsis; Skin Transplantation; Vancomycin

We report on a 54-year-old man with chronic lower back pain after recent streptococcus pneumoniae pulmonary infection, resulting in a mycotic aortic aneurysm and spondylodiscitis of the eighth vertebrae 6 months later. Successful surgical treatment and recurrence-free survival after 4 years are described.. Osteomyelitis by Streptococcus pneumoniae of the spine combined with contained rupture of a mycotic aortic aneurysm into lung and spine has not been reported to date. Mycotic aneurysms with pulmonary fistulas are reported to carry a mortality rate of up to 100%. Few cases have been reported with different operative and conservative strategies.. The mycotic aortic aneurysm was excised using extracorporeal circulation and replaced by a Dacron graft. The spondylitic section of the eighth thoracic vertebrae was radically resected, and a tricortical bone block from the iliac crest was inserted into the defect. To keep compartments separated, collagen sponges with antibiotic supplementation were used. A triple antibiotic therapy (Metronidazol 3 x 0.5 g/day, Cefotaxim 3 x 2 g/day, and Flucloxacillin 3 x 2 g/day) was prescribed for 6 weeks and changed to Clindamycin for 1 year thereafter.. The patient made a good recovery and is free of recurrence 4 years after surgery.. Lower back pain might be a projected pain. Particularly in older patients or in the presence of comorbidities resulting in an immunocompromised status, an aggressive workup may be indicated. Radical resection of inflammatory tissues, sparse use of implant material, and prolonged administration of antibiotics proved a successful strategy in this patient.

Topics: Aneurysm, Infected; Anti-Bacterial Agents; Aortic Aneurysm, Thoracic; Blood Vessel Prosthesis Implantation; Cefotaxime; Combined Modality Therapy; Discitis; Fistula; Floxacillin; Humans; Ischemia; Lung Diseases; Male; Metronidazole; Middle Aged; Nervous System Diseases; Osteomyelitis; Pneumococcal Infections; Pneumonia, Pneumococcal; Postoperative Complications; Respiratory Tract Fistula; Spinal Cord; Spinal Diseases; Spondylitis; Streptococcus pneumoniae; Thoracic Vertebrae; Tomography, X-Ray Computed; Tracheal Diseases; Treatment Outcome

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Cefotaxime; Creatine Kinase; Creatinine; Humans; Male; Muscle Weakness; Myoglobin; Pneumonia, Pneumococcal; Rhabdomyolysis; Spain; Streptococcus pneumoniae; Treatment Outcome

Streptococcus pneumoniae is the main etiological agent of community-acquired pneumonia. The aim of this work was to ascertain the resistance profiles of pneumococcus to penicillin and erythromycin and to analyse whether such profiles lead to different disease developments.. A retrospective analysis was carried out in 75 cases of pneumococcal pneumonia corresponding to hospitalized patients. Comorbidity factors were evaluated including their influence on the appearance of resistance.. 67 patients (89.3%) presented comorbidity factors. 49.3% isolates displayed some type of resistance: 38.6% to penicillin, 36% to erythromycin and 13.3% to cefotaxime. No relationship was observed between the severity of the pneumonia and antibiotic resistance. Complications and mortality were not influenced by the susceptibility of pneumococcus to antibiotics.. The increase in the resistance to antibiotics, especially erythromycin, makes betalactams the best choice for the treatment of pneumococcal pneumonia.

Topics: Adult; Aged; Anti-Bacterial Agents; Cefotaxime; Drug Resistance, Bacterial; Erythromycin; Female; Hospitalization; Humans; Male; Middle Aged; Penicillin Resistance; Pneumonia, Pneumococcal; Retrospective Studies

Topics: Adult; Anti-Bacterial Agents; Cefotaxime; Cephalosporins; Humans; Meningitis, Pneumococcal; Penicillin Resistance; Pneumococcal Infections; Pneumonia, Pneumococcal; Streptococcus pneumoniae

Topics: Aged; Cefotaxime; Community-Acquired Infections; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Follow-Up Studies; Humans; Infusions, Intravenous; Levofloxacin; Male; Microbial Sensitivity Tests; Ofloxacin; Pneumonia, Pneumococcal; Risk Assessment; Severity of Illness Index; Streptococcus pneumoniae; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Antigens, Bacterial; Bioterrorism; Cefotaxime; Ceftriaxone; Chlamydophila pneumoniae; Community-Acquired Infections; Humans; Legionnaires' Disease; Macrolides; Microbial Sensitivity Tests; Pneumonia; Pneumonia, Pneumococcal; Severe Acute Respiratory Syndrome; Streptococcus pneumoniae

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

Limited data are available about the impact of antimicrobial resistance on clinical outcomes in cases of pneumococcal pneumonia. This was studied in 146 persons hospitalized with invasive pneumonia due to Streptococcus pneumoniae (minimum inhibitory concentration of cefotaxime, > or = .25 microg/mL) who were identified through population-based active surveillance for the period of November 1994 through April 1996. Compared with matched control subjects who had infection with more-susceptible S. pneumoniae, the proportion of subjects who died or who were admitted to an intensive care unit did not differ significantly. Multivariable analysis showed no significant contribution of antimicrobial resistance to mortality or the requirement for care in an intensive care unit. The ability to detect an effect of antimicrobial resistance on these important outcome measures may have been influenced by aggressive multidrug empirical therapy in this group of hospitalized patients. Factors other than resistance, such as severity of illness at presentation and advance directive status ("do not resuscitate" orders), appear to have a stronger influence on pneumococcal pneumonia outcomes.

Topics: Adolescent; Adult; Aged; Bacteremia; Case-Control Studies; Cefotaxime; Cephalosporin Resistance; Child; Cohort Studies; Community-Acquired Infections; Hospitalization; Humans; Middle Aged; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Treatment Outcome

This study examined epidemiologic factors affecting mortality from pneumococcal pneumonia in 1995 through 1997.. Persons residing in a surveillance area who had community-acquired pneumonia requiring hospitalization and Streptococcus pneumoniae isolated from a sterile site were included in the analysis. Factors affecting mortality were evaluated in univariate and multivariate analyses. The number of deaths from pneumococcal pneumonia requiring hospitalization in the United States in 1996 was estimated.. Of 5837 cases, 12% were fatal. Increased mortality was associated with older age, underlying disease. Asian race, and residence in Toronto/Peel, Ontario. When these factors were controlled for, increased mortality was not associated with resistance to penicillin or cefotaxime. However, when deaths during the first 4 hospital days were excluded, mortality was significantly associated with penicillin minimum inhibitory concentrations of 4.0 or higher and cefotaxime minimum inhibitory concentrations of 2.0 or higher. In 1996, about 7000 to 12,500 deaths occurred in the United States from pneumococcal pneumonia requiring hospitalization.. Older age and underlying disease remain the most important factors influencing death from pneumococcal pneumonia. Mortality was not elevated in most infections with beta-lactam-resistant pneumococci.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cefotaxime; Cephalosporins; Child; Child, Preschool; Community-Acquired Infections; Drug Resistance, Microbial; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Penicillin Resistance; Pneumonia, Pneumococcal; United States

Topics: Aged; Amoxicillin; Cefotaxime; Cephalosporins; Drug Resistance, Microbial; France; Humans; Male; Microbial Sensitivity Tests; Penicillins; Pneumonia, Pneumococcal; Streptococcus pneumoniae

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Cefotaxime; Cefuroxime; Cephalosporins; Drug Therapy, Combination; Humans; Infant; Lung; Male; Pneumonia, Pneumococcal; Radiography; Streptococcus pneumoniae; Treatment Failure; Vancomycin

An extended-spectrum cephalosporin has been considered appropriate therapy for non-meningeal infections caused by drug-resistant Streptococcus pneumoniae. We report a toddler who had breakthrough bacteremia and meningitis develop because of drug-resistant pneumococcus while receiving treatment with cefotaxime and cefuroxime for pneumonia.

Topics: Bacteremia; Cefotaxime; Cefuroxime; Cephalosporin Resistance; Cephalosporins; Drug Resistance, Multiple; Humans; Infant; Infusions, Intravenous; Male; Meningitis, Pneumococcal; Pneumonia, Pneumococcal; Streptococcus pneumoniae

It has recently become apparent that overwhelming inflammatory reactions contribute to the high mortality rate associated with pneumococcal infection in immunocompetent hosts. Cefodizime (CEF) is an antibiotic that seems to be endowed with immunomodulating properties. To investigate the influence of CEF on the pulmonary inflammatory response induced by Streptococcus pneumoniae, we infected mice with repeated intranasal inoculations of 10(7) CFU of heat-killed fluorescein isothiocyanate-labeled bacteria, which are insensitive to the killing properties of the drug. CEF downregulated but did not abolish the strong polymorphonuclear leukocyte (PMN) recruitment induced by S. pneumoniae. PMN recruitment was not primarily mediated by leukotriene B4 in this model. The drug did not interfere with intrinsic mechanisms of phagocytosis by PMNs and alveolar macrophages. CEF totally abrogated the pneumococcus-induced tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) secretion in bronchoalveolar lavage fluid. The drug also prevented IL-6 release in lung homogenates and partly inhibited TNF-alpha, but it did not interfere with IL-1alpha secretion in the lungs of infected mice. The fractional and selective downregulation of inflammatory cells and cytokines by CEF suggests cell-specific and intracellular specific mechanisms of interaction of the drug. The immunomodulatory properties of CEF may help restrain excessive inflammatory reactions, thus contributing to the reported good clinical efficacy of the drug against lower respiratory tract infections.

Topics: Animals; Cefotaxime; Cephalosporins; Cytokines; Female; Inflammation Mediators; Mice; Neutrophils; Phagocytosis; Pneumonia, Pneumococcal

A model of pneumonia due to Streptococcus pneumoniae resistant to penicillin was developed in immunocompetent Wistar rats and was used to evaluate the efficacies of different doses of penicillin, cefotaxime, cefpirome, and vancomycin. Adult Wistar rats were challenged by intratracheal inoculation with 3 x 10(9) CFU of one strain of S. pneumoniae resistant to penicillin (MICs of penicillin, cefotaxime, cefpirome, and vancomycin, 2, 1, 0.5, and 0.5 microg/ml, respectively) suspended in brain heart broth supplemented with 0.7% agar. The rats experienced a fatal pneumonia, dying within 5 days and with peak mortality (70 to 80%) occurring 48 to 72 h after infection, and the bacterial counts in the lungs persisted from 8.87 +/- 0.3 log10 CFU/g of lung at 24 h of the infection to 9.1 +/- 0.3 log10 CFU/g at 72 h. Four hours after infection the animals were randomized into the following treatment groups: (i) control without treatment, (ii) penicillin G at 100,000 IU/kg of body weight every 2 h, (iii) penicillin G at 250,000 IU/kg every 2 h, (iv) cefotaxime at 100 mg/kg every 2 h, (v) cefpirome at 200 mg/kg every 2 h, and (vi) vancomycin at 50 mg/kg every 8 h. Two different protocols were used for the therapeutic efficacy studies: four doses of beta-lactams and one dose of vancomycin or eight doses of beta-lactams and two doses of vancomycin. Results of the therapy for experimental pneumonia caused by penicillin-resistant S. pneumoniae showed that initially, all the antimicrobial agents tested had similar efficacies, but when we prolonged the treatment, higher doses of penicillin, cefotaxime, and cefpirome were more effective than penicillin at lower doses in decreasing the residual bacterial titers in the lungs. Also, when we extended the treatment, vancomycin was more efficacious than penicillin at lower doses but was less efficacious than higher doses of penicillin or cefpirome. The model that we have developed is simple and amenable for inducing pneumonia in immunocompetent rats and could be used to explore the pathophysiology and to evaluate optimal therapy of this infection in the immunocompetent host.

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Cefpirome; Cephalosporins; Culture Media; Half-Life; Lung; Male; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Pneumonia, Pneumococcal; Rats; Rats, Wistar; Streptococcus pneumoniae; Vancomycin

The clinical course for a patient hospitalized with pneumonia and meningitis due to penicillin-, ceftriaxone-, and cefotaxime-resistant Streptococcus pneumoniae is described. The pneumonia and meningitis responded to antimicrobial therapy, but the patient died following rupture of an infected abdominal aortic aneurysm; gram-positive cocci resembling S. pneumoniae were detected within the aneurysm.

Topics: Aortic Aneurysm, Abdominal; Cefotaxime; Ceftriaxone; Cephalosporins; Drug Resistance, Microbial; Humans; Male; Meningitis, Bacterial; Middle Aged; Penicillins; Pneumonia, Pneumococcal; Streptococcus pneumoniae

The present study confirms that CBA/J mice are susceptible to several clinical isolates of Streptococcus pneumoniae, including four of five penicillin-susceptible and all five penicillin-resistant strains tested, thus providing the first noncompromised animal model for penicillin-resistant S. pneumoniae pneumonia. In this model, doses of penicillin G of 0.6 mg/kg of body weight given six times at 1-h intervals produced effective pulmonary clearance of a penicillin-susceptible strain (penicillin G MIC, 0.015 microgram/ml), while doses of 40 mg/kg given six times at 1-h intervals were required to clear a penicillin-resistant strain (penicillin G MIC, 1 microgram/ml). Imipenem (MIC, 0.25 microgram/ml) was the most active antibiotic tested against the penicillin-resistant strain, with a calculated dose of 0.42 mg/kg given six times at 1-h intervals, resulting in a 2-log decrease in the number of pulmonary bacteria. Comparable effects were seen with vancomycin (MIC, 0.5 microgram/ml), cefotaxime (MIC, 0.5 microgram/ml), and penicillin G at doses of 3.3, 5.5, and 31.0 mg/kg given six times at 1-h intervals, respectively. The pharmacokinetic profile of vancomycin in infected lungs was superior to those of the other antibiotics, especially in regard to the elimination half-life (215.4 min for vancomycin versus 15.0, 14.5, and 14.5 min for penicillin G, cefotaxime, and imipenem, respectively). Both imipenem and vancomycin allowed 90% survival when 40-mg/kg doses were administered twice a day beginning 5 days after infection. Survival rates with penicillin G (160-mg/kg doses) and cefotaxime (40-mg/kg doses) were 40 and 30%, respectively, while no saline-treated mice survived. The present study shows that the CBA/J mouse pneumonia model may be useful for evaluating antibiotic efficacies against penicillin-resistant pneumococcal pneumonia in immunocompetent individuals. Our data suggest that imipenem and vancomycin may be the most active agents against penicillin-resistant S. pneumoniae pneumonia.

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Disease Models, Animal; Imipenem; Lung; Male; Mice; Mice, Inbred CBA; Mice, Inbred ICR; Microbial Sensitivity Tests; Penicillin G; Penicillin Resistance; Pneumonia, Pneumococcal; Species Specificity; Streptococcus pneumoniae; Vancomycin

In an attempt to determine the susceptibility breakpoints for amoxycillin, co-amoxiclav and cefotaxime in pneumococcal pneumonia, a neutropenic mouse model was established and tested with two strains having different susceptibility to penicillins and cefotaxime. With a penicillin-sensitive strain (MIC/MBC = 0.01/0.01 mg/L) the minimum dosage tested achieving significant cure was 2 mg/kg for amoxycillin, co-amoxiclav and cefotaxime. For the penicillin-insensitive strain (MIC/MBC = 1/2 mg/L), the minimum dosage tested giving significant cure was 50 mg/kg for amoxycillin and co-amoxiclav but 100 mg/kg for cefotaxime. Our results support the belief that MICs of amoxycillin, co-amoxiclav and cefotaxime for pneumococcal strains of < or = 0.5 or < or = 1 mg/L can be considered as clinically relevant susceptibility breakpoints.

Topics: Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Animals; Cefotaxime; Cephalosporins; Clavulanic Acids; Disease Models, Animal; Drug Therapy, Combination; Female; Mice; Microbial Sensitivity Tests; Penicillins; Pneumonia, Pneumococcal; Streptococcus pneumoniae

Acute respiratory infection with penicillin-insensitive Streptococcus pneumoniae (MIC and MBC, 1 and 2 micrograms/ml, respectively) was established in guinea pigs. Intratracheal instillation of 0.5 ml of an overnight culture of S. pneumoniae concentrated 25 times (approximately 3 x 10(9) CFU) induced a bacteremic and fatal pneumonia in > 85% of untreated animals within 46 h, with a mean +/- standard deviation bacterial count of 8.83 +/- 1.11 log10 CFU in lung homogenates. This model was used to evaluate the efficacies of two doses each of amoxicillin, cefotaxime, and meropenem given 1 h after bacterial inoculation. The antibiotics were given at 8-h intervals for up to a total of four injections. The dose of 50 mg of any antibiotic per kg of body weight gave 66.6% survival, compared with 5.05% survival for untreated control animals (P < 0.001). A dose of 200 mg/kg gave a survival rate of 77.8% for meropenem and 83.3% for amoxicillin and cefotaxime, while survival for untreated controls was 11.1% (P < 0.001). Although antibiotic treatment decreased mortality compared with that in untreated controls, the antibiotics contributed to a high early (less than 9 h after bacterial inoculation) mortality, being 53.5% compared with only 6.06% for the untreated controls (P < 0.001). Quantitative cultures of the lungs of animals that died during the 46-h observation period or that were killed after this time showed a significant reduction in the numbers of organisms among treated animals compared with numbers among the control animals (P < 0.001). The described model is an appropriate system for evaluating antibiotic efficacy in invasive pulmonary infection caused by penicillin-insensitive S. pneumoniae.

Topics: Amoxicillin; Animals; Cefotaxime; Cephalosporins; Colony Count, Microbial; Disease Models, Animal; Female; Guinea Pigs; Lung; Meropenem; Penicillin Resistance; Penicillins; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Thienamycins

We previously demonstrated the efficacy of ceftriaxone (CRO), at 50 mg/kg of body weight every 12 h, against a highly penicillin-resistant (MIC, 4 micrograms/ml) Streptococcus pneumoniae strain with low-level resistance to CRO (MIC, 0.5 microgram/ml) in a leukopenic-mouse pneumonia model (P. Moine, E. Vallée, E. Azoulay-Dupuis, P. Bourget, J.-P. Bédos, J. Bauchet, and J.-J. Pocidalo, Antimicrob. Agents Chemother. 38:1953-1958, 1994). In the present study, we assessed the activity of CRO versus those of cefotaxime (CTX) and amoxicillin (AMO) against two highly penicillin- and cephalosporin-resistant S. pneumoniae strains (P40422 and P40984) (MICs of 2 and 8 for penicillin, 2 and 4 for AMO, and 4 and 8 for CRO or CTX, respectively). Against both strains, a greater than an 80% cumulative survival rate was observed with CRO at a dose of 100 or 200 mg/kg every 12 h (dose/MIC ratio, 25). With CTX, a high dosage of 400 mg/kg (dose/MIC ratio, 100 or 50) administered every 8 h (TID) was needed to protect 66 and 75% of the animals, respectively, with no statistically significant differences versus CRO. Against the P40422 strain, CRO (100 mg/kg) produced the greatest bactericidal effect, from the 8th to the 24th hour after a single injection (1.8-log-unit reduction over 24 h), and the fastest bacterial pulmonary clearance during treatment; with CTX, only multiple injections at a high dosage, i.e., 400 mg/kg TID, demonstrated a significant bactericidal effect. AMO in a high dosage, 400 mg/kg (dose/MIC ratio, 200) TID, showed good activity only against the P40422 strain. Despite the identical MICs of CTX and CRO, the longer time (3.6 to 4.6 h) that serum CRO concentrations remained above the MICs for the pathogens at a dose of 100 mg/kg resulted in greater efficacy versus CTX against highly penicillin- and cephalosporin-resistant S. pneumoniae strains.

Topics: Amoxicillin; Animals; Cefotaxime; Ceftriaxone; Cephalosporin Resistance; Cephalosporins; Disease Models, Animal; Female; Lung; Mice; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Pneumonia, Pneumococcal; Streptococcus pneumoniae

Penicillin-resistant strains of Streptococcus pneumoniae are now found worldwide, and strains with resistance to cephalosporin are being reported. The appropriate antibiotic therapy for pneumococcal pneumonia due to resistant strains remains controversial.. To examine the effect of resistance to penicillin and cephalosporin on mortality, we conducted a 10-year, prospective study in Barcelona of 504 adults with culture-proved pneumococcal pneumonia.. Among the 504 patients, 145 (29 percent) had penicillin-resistant strains of S. pneumoniae (minimal inhibitory concentration [MIC] of penicillin G, 0.12 to 4.0 micrograms per milliliter), and 31 patients (6 percent) had cephalosporin-resistant strains (MIC of ceftriaxone or cefotaxime, 1.0 to 4.0 micrograms per milliliter). Mortality was 38 percent in patients with penicillin-resistant strains, as compared with 24 percent in patients with penicillin-sensitive strains (P = 0.001). However, after the exclusion of patients with polymicrobial pneumonia and adjustment for other predictors of mortality, the odds ratio for mortality in patients with penicillin-resistant strains was 1.0 (95 percent confidence interval, 0.5 to 1.9; P = 0.84). Among patients treated with penicillin G or ampicillin, the mortality was 25 percent in the 24 with penicillin-resistant strains and 19 percent in the 126 with penicillin-sensitive strains (P = 0.51). Among patients treated with ceftriaxone or cefotaxime, the mortality was 22 percent in the 59 with penicillin-resistant strains and 25 percent in the 127 with penicillin-sensitive strains (P = 0.64) The frequency of resistance to cephalosporin increased from 2 percent in 1984-1988 to 9 percent in 1989-1993 (P = 0.002). Mortality was 26 percent in patients with cephalosporin-resistant S. pneumoniae and 28 percent in patients with susceptible organisms (P = 0.89). Among patients treated with ceftriaxone or cefotaxime, mortality was 22 percent in the 18 with cephalosporin-resistant strains and 24 percent in the 168 with cephalosporin-sensitive organisms (P = 0.64).. Current levels of resistance to penicillin and cephalosporin by S. pneumoniae are not associated with increased mortality in patients with pneumococcal pneumonia. Hence, these antibiotics remain the therapy of choice for this disease.

Topics: Adult; Aged; Bacteremia; Cefotaxime; Ceftriaxone; Cephalosporin Resistance; Community-Acquired Infections; Female; Humans; Incidence; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Penicillin G; Penicillin Resistance; Pneumonia, Pneumococcal; Prospective Studies; Spain; Streptococcus pneumoniae

Penicillin-resistant pneumococcal strains continue to spread. Some strains are also resistant to other antibiotics, including the cephalosporins. Better utilization of the 23-valent pneumococcal vaccine, which covers the serotypes responsible for 90% of pneumococcal infections, is an important step in combating resistance.

Topics: Aged; Algorithms; Bacterial Vaccines; Cefotaxime; Cephalosporin Resistance; Chest Tubes; Combined Modality Therapy; Decision Trees; Diagnosis, Differential; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Male; Microbial Sensitivity Tests; Penicillin Resistance; Pleural Effusion; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Rifampin; Streptococcus pneumoniae; Vancomycin

Fifty-eight consecutive patients with severe community-acquired pneumonia were studied prospectively during a three-year period. The group included 44 men and 14 women (mean age: 45.0 +/- 15.7 years). The cause of pneumonia was diagnosed in 35 (60.3 percent) cases, and the most common pathogens were Streptococcus pneumoniae (37.1 percent), Legionella pneumophila (22.8 percent) and Gram-negative bacilli (11.4 percent). The fact that Mycobacterium tuberculosis was present in four (11.4 percent) patients and Pneumocystis carinii in three (8.5 percent) is worthy of note. The overall death rate was 22.4 percent. More than 50 percent of deaths occurred within the first five days and were caused by septic shock, hemoptysis (tuberculosis) or hypoxia. However, hypoxia remains the main fatal complication and all late-occurring deaths (> 5 days) observed were due to this cause. These data could be important in planning strategies and protocols to improve prognosis.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; Cefotaxime; Critical Care; Erythromycin; Female; Humans; Legionnaires' Disease; Length of Stay; Male; Middle Aged; Pneumonia; Pneumonia, Pneumococcal; Pneumonia, Pneumocystis; Prognosis; Prospective Studies; Tuberculosis, Pulmonary

The therapeutic activity of FCE 22891 was compared with that of two new oral cephalosporins, cefuroxime axetil and cefixime against Streptococcus pneumoniae respiratory infection and subcutaneous abscesses induced by mixed aerobes and anaerobes in mice. In experimental pneumonia FCE 22891 was the most active antibiotic. In aerobic abscesses FCE 22891 proved the most active agent in infections induced by methicillin susceptible and resistant Staphylococcus aureus while all three compounds were very active, against Str. pyogenes. In abscesses caused by Gram-negative bacteria, FCE 22891 showed good and constant efficacy. Cefixime was the most active drug against the two susceptible strains of Escherichia coli and Enterobacter cloacae and also against resistant Esch. coli but was inactive against a strain of Ent. cloacae that produced cephalosporinase. Cefuroxime axetil was less active than the other two drugs against Gram-negative bacteria with adequate efficacy only against a susceptible strain of Ent. cloacae. FCE 22891 was more effective than cefixime and cefuroxime axetil in preventing and reducing the size of abscesses induced by Bacteroides fragilis 101. We conclude that FCE 22891, despite its short half life of 6 min in mice, exerts comparable and sometimes better activity than the two oral cephalosporins characterized by longer half lives.

Topics: Abscess; Animals; Anti-Bacterial Agents; Bacterial Infections; Bacteroides fragilis; Bacteroides Infections; Carbapenems; Cefixime; Cefotaxime; Cefuroxime; Cephalosporins; Female; Half-Life; Lung Diseases; Mice; Microbial Sensitivity Tests; Pneumonia, Pneumococcal

Topics: Adult; Aged; Cefotaxime; Female; Humans; Male; Meningitis, Pneumococcal; Middle Aged; Penicillin G; Penicillin Resistance; Pneumococcal Infections; Pneumonia, Pneumococcal; Streptococcus pneumoniae

Topics: Adolescent; Cefotaxime; Child; Child, Preschool; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Pneumonia; Pneumonia, Pneumococcal; Streptococcal Infections; Streptococcus pyogenes