rifampin and Pneumococcal-Infections

Septic arthritis due to Streptococcus Pneumoniae appears to be relatively uncommon. Single- or clustered-case histories constitute the majority of reports on pneumococcal septic arthritis. A 70-year-old man presented with a 7-day history of pain, erythema and swelling of the left shoulder. Physical examination of the left shoulder revealed a warm, swollen, erythematous, and markedly tender to light palpation. The patient was unable to elevate his arm more than 30 degrees without pain. Arthrocentesis performed on admission produced 30 cc of grossly purulent fluid whose culture demonstrated S. Pneumoniae. The septic arthritis was treated with intravenous vancomycin and imipenem. The antibiotics were substituted when the sensitivities were known with oral ciprofloxacin and rifampycin to complete 8 weeks' total treatment. On follow-up examination 1 year later, the patient has remained afebrile and asymptomatic without evidence of increasing joint effusion or acute joint inflammation. Pneumococcal arthritis is classically described as a painful monoarticular arthritis complicating an active pneumococcal infection, generally a primary pulmonary infection. Pneumococcal arthritis appears to be predominantly a disease affecting the elderly. Clinical presentation ranges from septicemia to indolent infection with few systemic symptoms. With adequate antibiotic therapy and aspiration or drainage of the joint, the prognosis for return of normal joint function appears to be excellent. Although pneumococcal organisms are not likely causes, this bacteria should certainly be considered as a possible cause of arthritis or prosthetic infection.

Topics: Aged; Anti-Bacterial Agents; Arthritis, Infectious; Ciprofloxacin; Drug Therapy, Combination; Humans; Male; Pneumococcal Infections; Rifampin; Shoulder Joint

Streptococcus pneumoniae is a major cause of disease and death that develops resistance to multiple antibiotics. DNA topoisomerase I (TopoI) is a novel pneumococcal drug target. TopoI is the sole type-I pneumococcal topoisomerase that regulates supercoiling homeostasis in this bacterium. In this study, a direct in vitro interaction between TopoI and RNA polymerase (RNAP) was detected by surface plasmon resonance. To understand the interplay between transcription and supercoiling regulation in vivo, genome-wide association of RNAP and TopoI was studied by ChIP-Seq. RNAP and TopoI were enriched at the promoters of 435 and 356 genes, respectively. Higher levels of expression were consistently measured in those genes whose promoters recruit both RNAP and TopoI, in contrast with those enriched in only one of them. Both enzymes occupied a narrow region close to the ATG codon. In addition, RNAP displayed a regular distribution throughout the coding regions. Likewise, the summits of peaks called with MACS tool, mapped around the ATG codon in both cases. However, RNAP showed a broader distribution towards ATG-downstream positions. Remarkably, inhibition of RNAP with rifampicin prevented the localization of TopoI at promoters and, vice versa, inhibition of TopoI with seconeolitsine prevented the binding of RNAP to promoters. This indicates a functional interplay between RNAP and TopoI. To determine the molecular factors responsible for RNAP and TopoI co-recruitment, we looked for DNA sequence motifs. We identified a motif corresponding to a -10-extended promoter for TopoI and for RNAP. Furthermore, RNAP was preferentially recruited to genes co-directionally oriented with replication, while TopoI was more abundant in head-on genes. TopoI was located in the intergenic regions of divergent genes pairs, near the promoter of the head-on gene of the pair. These results suggest a role for TopoI in the formation/stability of the RNAP-DNA complex at the promoter and during transcript elongation.

Topics: DNA Topoisomerases, Type I; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Gene Expression Regulation, Bacterial; Genome, Bacterial; Nucleotide Motifs; Pneumococcal Infections; Promoter Regions, Genetic; Rifampin; Streptococcus pneumoniae; Surface Plasmon Resonance; Transcription, Genetic

Cerebritis y abscesos cerebrales por Streptococcus pneumoniae en un recien nacido.

Topics: Anti-Bacterial Agents; Anticonvulsants; Bacteremia; Brain Abscess; Bronchiolitis; Cardiotonic Agents; Cerebral Hemorrhage; Drug Therapy, Combination; Fatal Outcome; Humans; Immunocompromised Host; Infant, Newborn; Magnetic Resonance Imaging; Male; Meningitis, Pneumococcal; Pneumococcal Infections; Respiratory Syncytial Virus Infections; Rifampin; Spleen; Streptococcus pneumoniae; Vancomycin

Among 5,043 invasive pneumococcal disease (IPD) isolates identified through South African national surveillance from 2003 to 2007, we estimated the effect of trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis on antimicrobial resistance. Patients on TMP-SMX prophylaxis were more likely to have a pneumococcal isolate nonsusceptible to TMP-SMX, penicillin, and rifampin. TMP-SMX nonsusceptibility was associated with nonsusceptibility to penicillin, erythromycin, and rifampin and multidrug resistance. This study informs empirical treatment of suspected IPD in patients with a history of TMP-SMX use.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Erythromycin; Female; Humans; Infant; Infant, Newborn; Longitudinal Studies; Male; Middle Aged; Penicillins; Pneumococcal Infections; Population Surveillance; Rifampin; South Africa; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Alcoholism; Amoxicillin; Aneurysm, Infected; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Aortic Aneurysm, Abdominal; Aortitis; Blood Vessel Prosthesis Implantation; Combined Modality Therapy; Discitis; Disease Susceptibility; Humans; Lumbar Vertebrae; Male; Middle Aged; Naproxen; Pneumococcal Infections; Psoas Abscess; Pulmonary Disease, Chronic Obstructive; Rifampin; Tomography, X-Ray Computed

Topics: Abdominal Abscess; Adult; Anti-Bacterial Agents; Cefotaxime; Humans; Male; Pelvis; Pneumococcal Infections; Pristinamycin; Retroperitoneal Space; Rifampin; Streptococcus pneumoniae; Young Adult

A 76-year-old woman had a chest pain and high fever, and was admitted to the intensive care unit diagnosed as acute pericarditis. Enhanced CT-scan showed a 47-mm aneurysm in the aortic arch which seemed to be impending rupture and the part of the aorta looked like a pseudoaneurysm. Emergent total aortic arch replacement with a rifampicin-bonded Dacron graft was performed. Pericardial effusion was purulent and the aorta was infected with pus discharge in the aortic wall. There were some ulcerations on the surface of the luminal wall of the aorta. One of them was penetrating into the pericardial space causing a pseudoaneurysm. Both pericardial effusion and excised aortic wall were sent to culture study and resulted in positive for Streptococcus pneumoniae. The infection of the aorta, with erosion into the pericardial space, seemed to be the cause of purulent pericarditis. Antibiotic therapy was commenced immediately after surgery and continued for four weeks. Though she had neurological deficit after surgery, her infection was well controlled and there was no recurrence of infection 11 months after surgery.

Topics: Aged; Aneurysm, False; Aneurysm, Infected; Anti-Bacterial Agents; Aortic Aneurysm, Thoracic; Aortography; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Combined Modality Therapy; Drug Therapy, Combination; Female; Humans; Penicillin G; Pericardial Effusion; Pericarditis; Pneumococcal Infections; Polyethylene Terephthalates; Prosthesis Design; Rifampin; Tomography, X-Ray Computed; Treatment Outcome

We describe the clinical course of a previously healthy 20-month-old toddler admitted with high fever and leukocytosis. Blood culture grew Streptococcus pneumoniae serotype 19A, belonging to the ST663 clone, highly resistant to penicillin, ceftriaxone, and erythromycin. The same clone with identical antibiogram was isolated from the nasopharynx of another three of the other five healthy children attending the same daycare center as the patient. This case exemplifies the potential problems posed by highly-resistant S. pneumoniae serotype 19A, an emerging pathogen worldwide.

Topics: Anti-Bacterial Agents; Bacteremia; Carrier State; Child Day Care Centers; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Israel; Pneumococcal Infections; Rifampin; Serotyping; Streptococcus pneumoniae; Vancomycin

Otitis, pneumonia, and meningitis are tissue-based pneumococcal infections that can be associated with biofilms. The emergence of phenotypic rough variants, also known as acapsular small-colony variants, is essential for pneumococcal biofilm formation. These rough variants can increase nearly 100-fold in biofilms over time and can arise through single nucleotide polymorphisms (SNPs), deletions, or tandem duplications in the first gene of the capsular operon, cps3D. We detected a 100-fold increase in rifampin-resistant (Rif(r)) mutants in biofilms compared to planktonic cultures using a nonvaccine serotype 3 strain, which is causing an increasing number of cases of otitis in the 7-valent pneumococcal conjugate vaccine era. Since both rough variants and Rif(r) strains can arise through SNPs, they could emerge due to alteration of the mismatch repair (MMR) system. The Hex system, a pneumococcal MMR system, repairs mismatches during replication and transformation. In this study, no mutations were detected in the hexAB gene sequences among several rough variants with unique mutations in the cps3D gene. Within a hexA null mutant grown in broth, we detected only a 17.5-fold increase in rough variants compared to the wild-type parental strain. Taken together, these data suggest that mutations in the hex genes and modulation of hexA activity are unlikely to account for the generation of biofilm-derived rough variants.

Topics: Antibiotics, Antitubercular; Bacterial Capsules; Bacterial Proteins; Biofilms; DNA Mismatch Repair; DNA-Binding Proteins; DNA, Bacterial; Drug Resistance, Bacterial; Humans; Mutation; Pneumococcal Infections; Polymorphism, Single Nucleotide; Rifampin; Sequence Analysis, DNA; Streptococcus pneumoniae; Uridine Diphosphate Glucose Dehydrogenase; Virulence

The empiric choice of initial antibiotherapy in osteoarticular infections in infants and children must take into consideration the actual epidemiology of principal pathogens, their respective antibiotic sensitivity profile, their pharmacokinetic and pharmacodynamic properties and the results of efficacy clinical studies. After a review of recent data concerning these four major points, the Paediatric Infectious Diseases Group of the French Society of Paediatrics (GPIP) has proposed guidelines for initial recommended schemes of antimicrobial therapy in acute and non complicated osteoarticular infections in infants and children.

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bone Diseases, Infectious; Child; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Infant; Joint Diseases; Kingella kingae; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Neisseriaceae Infections; Penicillins; Pneumococcal Infections; Pristinamycin; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fluoroquinolone-resistant Streptococcus pneumoniae in children in South Africa.. 21,521 cases of invasive pneumococcal disease were identified by active national surveillance between 2000 and 2006, with enhanced surveillance at 15 sentinel hospitals in seven provinces introduced in 2003. We screened 19,404 isolates (90% of cases) for ofloxacin resistance and measured levofloxacin minimum inhibitory concentrations (MICs) for all isolates that were ofloxacin resistant. Non-susceptibility to levofloxacin was defined as an MIC of 4 mg/L or more. Nasopharyngeal pneumococcal carriage was assessed in 65 children in two tuberculosis hospitals where invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae had been detected.. 12 cases of invasive pneumococcal disease were identified as being non-susceptible to levofloxacin, all in children aged under 15 years. All isolates were rifampicin resistant. Outcome was known for 11 of these patients; five (45%) died. Invasive disease caused by levofloxacin-non-susceptible S pneumoniae was associated with a history of tuberculosis treatment (eight [89%] of nine children with non-susceptible isolates had a history of treatment vs 396 [18%] of 2202 children with susceptible isolates; relative risk [RR] 35.78, 95% CI 4.49-285.30) and nosocomial invasive pneumococcal disease (eight [80%] of ten children with non-susceptible isolates had acquired infection nosocomially vs 109 [4%] of 2709 with susceptible isolates; RR 88.96, 19.10-414.29). 31 (89%) of 35 pneumococcal carriers had bacteria that were non-susceptible to levofloxacin.. Our data suggest that the use of fluoroquinolones to treat multidrug-resistant tuberculosis in children has led to the emergence of invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae and its nosocomial spread.

Topics: Adolescent; Anti-Bacterial Agents; Antitubercular Agents; Child; Child, Preschool; Cross Infection; Cross-Sectional Studies; Drug Resistance, Bacterial; Female; Humans; Infant; Levofloxacin; Male; Ofloxacin; Pneumococcal Infections; Population Surveillance; Rifampin; Risk Factors; South Africa; Statistics, Nonparametric; Streptococcus pneumoniae; Tuberculosis, Multidrug-Resistant; World Health Organization

Topics: Anti-Bacterial Agents; Antitubercular Agents; Drug Resistance, Bacterial; Humans; Ofloxacin; Pneumococcal Infections; Rifampin; South Africa; Tuberculosis, Multidrug-Resistant; World Health Organization

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

We describe an effort to reduce transmission of a multidrug-resistant Streptococcus pneumoniae (MDRSP) in a long-term-care facility (LTCF).. Longitudinal cross-sectional study.. An LTCF in New York City with ongoing disease due to an MDRSP strain among residents with AIDS since a 1995 outbreak. The MDRSP outbreak strain was susceptible to vancomycin but not to other antimicrobials tested, including fluoroquinolones.. Residents and staff members of the LTCF during 1999 through 2001.. Implementing standard infection control measures, and developing and implementing "enhanced standard" infection control measures, modified respiratory droplet prevention measures to reduce inter-resident transmission.. Before the intervention, nasopharyngeal carriage of the MDRSP outbreak strain was detected in residents with AIDS and residents with tracheostomies who were not dependent on mechanical ventilation. The prevalence of nasopharyngeal carriage of the MDRSP outbreak strain was 7.8% among residents who had AIDS and 14.6% among residents with tracheostomies. After training sessions on standard and enhanced standard infection control measures, the staff appeared to have good knowledge and practice of the infection control measures. After the intervention, new transmission among residents with tracheostomies was prevented; however, these residents were prone to persistent tracheal carriage and needed ongoing enhanced standard infection control measures. Ongoing transmission among residents with AIDS, a socially active group, was documented, although fewer cases of disease due to the outbreak strain occurred.. Infection control contributed to less transmission of MDRSP in the LTCE Additional strategies are needed to reduce transmission and carriage among certain resident populations.

Topics: Antibiotic Prophylaxis; Antibiotics, Antitubercular; Bacterial Vaccines; Carrier State; Cross Infection; Cross-Sectional Studies; Drug Resistance, Bacterial; Drug Resistance, Multiple; Fluoroquinolones; Health Facilities; Humans; Long-Term Care; Longitudinal Studies; Nasopharyngeal Diseases; New York; Pneumococcal Infections; Prevalence; Rifampin; Risk Factors; Serotyping; Streptococcus pneumoniae; Treatment Outcome

A total of 103 (0.7%) of 14,236 Streptococcus pneumoniae isolates collected in four Spanish hospitals from 1989 to 2003 were resistant to rifampin (MICs, 4 to 512 microg/ml). Only sixty-one (59.2%) of these isolates were available for molecular characterization. Resistance was mostly related to human immunodeficiency virus (HIV) infection in adult patients and to conjunctivitis in children. Thirty-six different pulsed-field gel electrophoresis patterns were identified among resistant isolates, five of which were related to international clones (Spain23F-1, Spain6B-2, Spain9V-3, Spain14-5, and clone C of serotype 19F), and accounted for 49.2% of resistant isolates. Single sense mutations at cluster N or I of the rpoB gene were found in 39 isolates, while double mutations, either at cluster I, at clusters I and II, or at clusters N and III, were found in 14 isolates. The involvement of the mutations in rifampin resistance was confirmed by genetic transformation. Single mutations at clusters N and I conferred MICs of 2 microg/ml and 4 to 32 microg/ml, respectively. Eight isolates showed high degrees of nucleotide sequence variations (2.3 to 10.8%) in rpoB, suggesting a recombinational origin for these isolates, for which viridans group streptococci are their potential gene donors. Although the majority of rifampin-resistant isolates were isolated from individual patients without temporal or geographical relationships, the clonal dissemination of rifampin-resistant isolates was observed among 12 HIV-infected patients in the two hospitals with higher rates of resistance.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Base Sequence; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Gene Transfer, Horizontal; Hospitals; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Phylogeny; Pneumococcal Infections; Rifampin; Sequence Analysis, DNA; Spain; Streptococcus pneumoniae

To determine the mechanism of rifampicin resistance in Streptococcus pneumoniae in Taiwan.. Rifampicin resistance was investigated with respect to the rpoB gene in 23 invasive S. pneumoniae isolates collected from 1996 to 2001. PCR and molecular typing were used for genetic and epidemiological analyses. Transformation was used to determine the functional gene for resistance.. Twenty-two of 23 isolates carried at least one mutation at either cluster I or III of rpoB; the most frequent mutation found in 21 isolates (91%) was histidine (H499) to asparagine or tyrosine at position 499, followed by isoleucine to valine (I624V) at position 624 in 16 isolates (70%), tyrosine to phenylalanine (Y589F) at position 589 in 14 isolates (60.9%) and isoleucine to valine (I608V) at position 608 in 13 isolates (56.5%). Less-frequent mutations were also identified: D489V, R597F, N623E, N623S, N669D, Q671K, Y674F and A683V. High-level rifampicin resistance was observed in isolates with a mutation at position 499 or 489. Mutations other than at position 499 or 489 played little role in or had no relation to rifampicin resistance. No dominant epidemic strain was observed with ribotyping, multilocus sequence typing, or serotyping.. Rifampicin resistance among multidrug-resistant S. pneumoniae in Taiwan was mostly caused by rpoB mutations.

Topics: Amino Acid Substitution; Antibiotics, Antitubercular; Bacterial Proteins; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; Genes, Bacterial; Microbial Sensitivity Tests; Molecular Epidemiology; Pneumococcal Infections; Polymorphism, Restriction Fragment Length; Reverse Transcriptase Polymerase Chain Reaction; Ribotyping; Rifampin; Streptococcus pneumoniae; Taiwan; Transformation, Bacterial

To investigate the antibiotics-resistance type and molecular epidemiology of Streptococcus pneumoniae isolated from children in Hangzhou.. The sensitivities of 323 strains of Streptococcus pneumoniae to 9 antibiotics were determined in vitro by Kirby-Bauer diffuse methods, and MICs of penicillin and cefotaxime were determined by E-test methods.. Among all 323 strains isolated from children during the period from August 2001 to July 2002, 136 strains (42.1%) were sensitive to penicillin, while 57 strains (17.7%) were penicillin-resistant. Penicillin MICs ranged from 0.012 microg/ml to 4.0 microg/ml. All the strains were sensitive to cefotaxime and its MICs ranged from 0.012 microg/ml to 4.0 microg/ml. The most resistant antibiotic was erythromycin and it's resistant-rate was as high as 90.7%, followed by tetracycline (87.6%), trimethoprim-sulfamethoxazole (48.6%) and chloromycetin (14.9%). Totally 197 strains (61.0%) were multi-drug-resistant pneumococci and most of them were resistant to trimethoprim-sulfamethoxazole, erythromycin and tetracycline at the same time. Two strains (0.6%) were resistant to rifampin and none was resistant to vancomycin and ofloxacin. BOX PCR typing was carried out and no overwhelming fingerprinting pattern was found among penicillin resistant Streptococcus pneumoniae strains which were isolated from patients, while the banding patterns were always similar or identical among the strains isolated from the same specimen or from the same patient at different time, respectively.. The antibiotics-resistant rate of pneumococci was high in Hangzhou, but the third-generation cephalosporins were still the best antibiotics against Streptococcus pneumoniae. One child could be infected or colonized by more than one pneumococci clone at the same or different time.

Topics: Anti-Bacterial Agents; Cefotaxime; Child, Preschool; China; Chloramphenicol; Drug Resistance, Bacterial; Erythromycin; Female; Humans; Infant; Male; Microbial Sensitivity Tests; Ofloxacin; Penicillins; Pneumococcal Infections; Respiratory Tract Infections; Rifampin; Streptococcus pneumoniae; Tetracycline; Trimethoprim

Topics: Aged; Anti-Infective Agents; Arthritis, Infectious; Arthroplasty, Replacement, Knee; Azithromycin; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Male; Ofloxacin; Pneumococcal Infections; Prosthesis-Related Infections; Rifampin; Vancomycin

Rifampin is recommended for combination therapy of meningitis due to beta-lactam-resistant Streptococcus pneumoniae. High-level rifampin resistance (MIC, > or =4 mg/liter) has been mapped to point mutations in clusters I and III of rpoB of the pneumococcus. The molecular basis of low-level resistance (MICs, > or =0.5 and <4 mg/liter) was analyzed. Spontaneous mutants of clinical pneumococcal isolates were selected on Columbia sheep blood agar plates containing rifampin at 0.5, 4, 10, or 50 mg/liter. Low-level resistance could be assigned to mutations in cluster II (I(545)N, I(545)L). Sensitive (MIC, <0.048 mg/liter) wild-type strains acquired low-level resistance at a rate approximately 10 times higher than that at which they acquired high-level resistance (average mutation frequencies, 2.4 x 10(-7) for low-level resistance versus 2.9 x 10(-8) for high-level resistance [P < 0.0001]). In second-step experiments, the frequencies of mutations from low- to high-level resistance were over 10 times higher than the frequencies of mutations from susceptibility to high-level resistance (average mutation frequencies, 7.2 x 10(-7) versus 5.0 x 10(-8) [P < 0.001]). Mutants with low-level resistance were stable upon passage. Sequencing of a clinical isolate with low-level resistance (MIC, 0.5 mg/liter) revealed a Q(150)R mutation upstream of cluster I. The frequencies of mutations to high-level resistance for this strain were even higher than the rates observed for the in vitro mutants. Therefore, a resistance-mediating mutation located outside clusters I, II, and III has been described for the first time in the pneumococcus. In vitro low-level rifampin resistance in S. pneumoniae could be mapped to cluster II of rpoB. Mutants of pneumococcus with low-level resistance may be selected in vivo during therapy in tissue compartments with low antibiotic concentrations and play a role in the development of resistance.

Topics: Antibiotics, Antitubercular; DNA-Directed RNA Polymerases; DNA, Bacterial; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Mutation; Pneumococcal Infections; Reverse Transcriptase Polymerase Chain Reaction; Rifampin; Streptococcus pneumoniae; Transformation, Bacterial

Alginate microparticles were developed as oral sustained delivery carriers for antitubercular drugs in order to improve patient compliance. In the present study, pharmacokinetics and therapeutic effects of alginate microparticle encapsulated antitubercular drugs, i.e. isoniazid, rifampicin and pyrazinamide were examined in guinea pigs. Alginate microparticles containing antitubercular drugs were evaluated for in vitro and in vivo release profiles. These microparticles exhibited sustained release of isoniazid, rifampicin and pyrazinamide for 3-5 days in plasma and up to 9 days in organs. Peak plasma concentration (Cmax), Tmax, elimination half-life (t1/2e) and AUC0- infinity of alginate drugs were significantly higher than those of free drugs. The encapsulation of drug in alginate microparticles resulted in up to a nine-fold increase in relative bioavailability compared with free drugs. Chemotherapeutic efficacy of alginate drug microspheres against experimental tuberculosis showed no detectable cfu values at 1:100 and 1:1000 dilutions of spleen and lung homogenates. Histopathological studies further substantiated these observations, thus suggesting that application of alginate-encapsulated drugs could be useful in the effective treatment of tuberculosis.

Topics: Administration, Oral; Alginates; Animals; Antibiotics, Antitubercular; Antitubercular Agents; Area Under Curve; Drug Compounding; Excipients; Guinea Pigs; Half-Life; Hydrogels; Isoniazid; Pneumococcal Infections; Pyrazinamide; Rifampin; Solubility

Potential alternatives, including linezolid, adjunctive rifampin, and moxifloxacin, were evaluated against vancomycin-tolerant (P9802-020) and vancomycin-susceptible clinical isolates of Streptococcus pneumoniae in an in vitro pharmacodynamic model. Vancomycin exhibited maximal killing of 2-log(10) CFU/ml against P9802-020. Linezolid, moxifloxacin, and linezolid plus rifampin exhibited 99.9% killing against both isolates. These alternatives should be considered for further evaluation against vancomycin-tolerant S. pneumoniae.

Topics: Acetamides; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Drug Tolerance; Humans; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Pneumococcal Infections; Rifampin; Streptococcus pneumoniae; Vancomycin; Vancomycin Resistance

Streptococcus pneumoniae, a common pathogen in pediatric infections, has become resistant to penicillin and make these infections difficult to treat. Rifampin and chloramphenicol have been recommended as alternative therapies, since they are less costly and more accessible to communities with limited resources. However, their use may be restricted by the differing levels of resistance found in target populations. The objective was to determine minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) for chloramphenicol and rifampin in strains of S. pneumoniae. These strains were newly isolated from children under age 5 that had demonstrated systemic infections and meningitis. A subgroup of 107 isolates of S. pneumoniae was selected from 324 strains isolated during a period of 2 years (1994-1996). Among these isolates, 60 were penicillin-resistant and 47 were susceptible; 53 isolates were from children with meningitis. MIC and MBC for chloramphenicol and rifampicin were obtained by standard methods recommended by the National Committee for Clinical Laboratory Standards (NCCLS). S. pneumoniae ATCC strain 49619 served as the control. An isolate was considered susceptible to chloramphenicol when MIC = 4 microg/ml and resistant when MIC = 8 microg/ml. A strain was considered susceptible to rifampin when MIC = 1 microg/ml and resistant when MIC = 4 microg/ml. MBC was determined by recording the lower concentration of the antibiotic that inhibited 99.9% of the initial inoculum. Chloramphenicol resistance was found in 21% of the 107 isolates. In the group susceptible to penicillin, 11% were resistant to chloramphenicol and in the group resistant to penicillin 28% was resistant to chloramphenicol as well. MBC was found > 4 microg/ml in 28% of the isolates susceptible to penicillin and in 60% of the resistant isolates. No isolates were found resistant to rifampin. However, 2 penicillin resistant isolates showed CBM > 1 microg/ml to rifampin, and one with CIM = 1 microg/ml had a MBC to rifampicin of 16 microg/ml. Meningitis isolates showed higher CIM and CBM than the group of total isolates. These data suggest that chloramphenicol is not recommended for invasive infections caused by S. pneumoniae in Colombia. Rifampin is a more effective therapy in combination with other antibiotics for treatment of this kind of infections. Further studies are necessary to clarify the significance of low levels of MBC to rifampin found in some strains, sin

Topics: Anti-Bacterial Agents; Child, Preschool; Chloramphenicol; Colombia; Humans; Infant; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Pneumococcal Infections; Rifampin; Streptococcus pneumoniae

A multidrug-resistant strain of Streptococcus pneumoniae was isolated in The Netherlands during a nosocomial outbreak among 36 patients who mainly had chronic obstructive pulmonary disease. After the commencement of barrier nursing and short-term ceftriaxone-rifampin eradication therapy, the epidemic ceased. However, eradication therapy failed in 3 patients, and follow-up investigation of these patients showed the emergence of rifampin-resistant isolates.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Cross Infection; DNA-Directed RNA Polymerases; Drug Resistance, Multiple, Bacterial; Humans; Molecular Sequence Data; Penicillin Resistance; Pneumococcal Infections; Pulmonary Disease, Chronic Obstructive; Rifampin; Streptococcus pneumoniae

Patients who undergo splenectomy and recipients of allogeneic marrow (alloBMT) or peripheral stem cell transplantation are at increased risk of overwhelming infection from encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. As prophylaxis against these pathogens splenectomised patients are immunised and may also receive antibiotics for life. We report relapsing overwhelming sepsis caused by penicillin-resistant pneumococcus in a patient who was immunised and received prophylactic phenoxymethylpenicillin for 8 months following splenectomy and matched unrelated donor (MUD) marrow transplantation for refractory T cell lymphoma. No obvious focus of sepsis was found during any of the three episodes and S. pneumoniae serogroup 6, subtype 6B was isolated from blood cultures on each occasion. He was treated with i.v. cephalosporins, as the organisms were resistant to penicillin with a minimum inhibitory concentration (MIC) of 2.0, and there was complete resolution of symptoms each time. In the light of recurrent sepsis with this penicillin-resistant organism the decision was made to give prophylactic levofloxacin for the next 12 months. This case illustrates that the choice of prophylactic regimen and the treatment of sepsis in immunocompromised patients remain difficult and challenging issues.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Bone Marrow Transplantation; Carmustine; Cefotaxime; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Cytomegalovirus Infections; Doxorubicin; Drug Therapy, Combination; Etoposide; Humans; Idarubicin; Immunocompromised Host; Immunosuppressive Agents; Levofloxacin; Lymphoma, T-Cell; Male; Melphalan; Ofloxacin; Penicillin Resistance; Pneumococcal Infections; Prednisone; Recurrence; Rifampin; Splenectomy; Streptococcus pneumoniae; Transplantation Conditioning; Vincristine

This statement provides guidelines for therapy of children with serious infections possibly caused by Streptococcus pneumoniae. Resistance of invasive pneumococcal strains to penicillin, cefotaxime, and ceftriaxone has increased over the past few years. Reports of failures of cefotaxime or ceftriaxone in the treatment of children with meningitis caused by resistant S pneumoniae necessitates a revision of Academy recommendations. For nonmeningeal infections, modifications of the initial therapy need to be considered only for patients who are critically ill and those who have a severe underlying or potentially immunocompromising condition or patients from whom a highly resistant strain is isolated. Because vancomycin is the only antibiotic to which all S pneumoniae strains are susceptible, its use should be restricted to minimize the emergence of vancomycin-resistant organisms. Patients with probable aseptic (viral) meningitis should not be treated with vancomycin. These recommendations are subject to change as new information becomes available.

Topics: Anti-Bacterial Agents; Child; Diagnosis, Differential; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Meningitis, Bacterial; Meningitis, Viral; Microbial Sensitivity Tests; Pneumococcal Infections; Rifampin; Vancomycin

Primary vertebral osteomyelitis in a rare presentation of pneumococcal infection especially in an asymptomatic patient with no primary focus of infection. This report describes a patient who presented with lower back pain in which the magnetic resonance imaging showed little evidence of L1 and L2 vertebral body destruction. Cultures from these vertebral bodies grew penicillin and third-generation resistant pneumococcus. The patient was treated successfully with 6 weeks of vancomycin and rifampin.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Humans; Middle Aged; Osteomyelitis; Pneumococcal Infections; Rifampin; Spinal Diseases; Streptococcus pneumoniae; Vancomycin

39 children with prolonged nasopharyngeal carriage (48-328 days) of intermediately to highly penicillin-resistant pneumococci (PRP) were treated for 7 days with rifampicin in combination with amoxicillin (n = 18) erythromycin (n = 17) or clindamycin (n = 4), according to resistance pattern. In all children, except for 1 carrying a rifampicin-resistant strain, control cultures from the nasopharynx 1-2 weeks after the last antibiotic dosage, yielded no growth of PRP. In 2 brothers, PRP with the same serogroup and resistance pattern were found in nasopharynx 10 weeks after the antibiotic treatment. These preliminary findings indicate that antibiotic regimens including rifampicin are effective in eradicating nasopharyngeal carriage, but reappearance of the same strain may occur after several weeks. Such treatments should be given with caution due to the risk of selecting rifampicin-resistant strains. Further controlled studies are needed to determine the optimal combination of antibiotics and appropriate duration of therapy.

Topics: Amoxicillin; Anti-Bacterial Agents; Antibiotics, Antitubercular; Carrier State; Child; Child, Preschool; Clindamycin; Drug Resistance, Microbial; Drug Therapy, Combination; Erythromycin; Humans; Infant; Infant, Newborn; Nasopharyngeal Diseases; Nasopharynx; Penicillin Resistance; Penicillins; Pneumococcal Infections; Rifampin; Sweden

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

Although Streptococcus pneumoniae is the leading cause of community-acquired pneumonia in humans, the mechanism whereby the organism penetrates lung tissue is poorly understood. In the present study we have examined the capacity of pneumococci to penetrate A549 cells, a human lung alveolar carcinoma (type II pneumocyte) cell line. Not all clinical S. pneumoniae isolates initially tested were capable of penetration of the cells, as judged by resistance to extracellular antibiotics. The presence of a polysaccharide capsule also significantly reduced the capacity to both adhere to and penetrate A549 cells. Electron micrographs showed the presence of pneumococci enclosed within vacuoles of intact A549 cells, but bacteria were also seen free in the cytoplasm of damaged cells. Ongoing bacterial DNA, RNA, or protein synthesis was not essential for uptake of pneumococci by A549 cells, and uptake was not diminished by pretreatment of the pneumococci with trypsin. However, inhibition of A549 microfilament assembly with cytochalasin D abolished the phenomenon.

Topics: Bacterial Adhesion; Bacterial Capsules; Bacterial Proteins; Cells, Cultured; Chloramphenicol; Ciprofloxacin; Cytochalasin D; DNA, Bacterial; Enzyme Inhibitors; Epithelium; Humans; Microscopy, Electron; Pneumococcal Infections; Protein Synthesis Inhibitors; Pulmonary Alveoli; Rifampin; RNA, Bacterial; Streptococcus pneumoniae; Trypsin; Tumor Necrosis Factor-alpha

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 cases are reported of two infants with pneumococcal meningitis in whom initial antibiotic treatment was ineffective despite the organisms being sensitive to the drugs used. A clinical and radiological diagnosis of meningoencephalitis was made. A rapid improvement followed the addition of rifampicin treatment.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Infant; Infant, Newborn; Lactams; Male; Meningoencephalitis; Microbial Sensitivity Tests; Pneumococcal Infections; Rifampin; Tomography, X-Ray Computed

To investigate a cluster of invasive pneumococcal disease in children 8 to 26 months of age, using standard microbiological procedures and ribosomal DNA gene-restriction patterns to characterize the outbreak strain.. Outbreak investigation.. A family child-care home with six children in Baltimore, Md.. During an 8-day period, three of the six children in the family child-care home had febrile illnesses with pneumococcal bacteremia, and a fourth had purulent pneumococcal conjunctivitis. Type 12F Streptococcus pneumoniae was isolated from the four ill children and from the nasopharynges of the two healthy children. Ribotyping revealed all outbreak isolates had an identical ribotype pattern. Administration of rifampin to the children did not eradicate carriage of the organism.. Our data demonstrate that child care provides an opportunity for outbreak of invasive pneumococcal disease in young children. This observation suggests a need for increased alertness for clusters of pneumococcal disease in young children in child-care facilities and underscores the necessity for a pneumococcal vaccine that is effective in infants and young children.

Topics: Bacteremia; Child Day Care Centers; Cluster Analysis; Disease Outbreaks; Drug Resistance, Microbial; Family Characteristics; Female; Humans; Infant; Male; Pneumococcal Infections; Restriction Mapping; Rifampin; Serotyping; Streptococcus pneumoniae

Streptococcus pneumoniae, type 23F, resistant to penicillin (MIC, 2 micrograms/mL) and multiple other antimicrobic agents, was isolated from middle ear fluid of a child with otitis media attending a day care center in Ohio. To determine the extent of spread of this strain, nasopharyngeal culture surveys were done, and 52 carriers were identified among 250 children attending the index day care center. No carriers were found among 121 children at two other day care centers in the same urban area. Use of prophylactic doses of antibiotics (P < .001) and frequent use of antibiotics (P < 0.001) were risk factors for nasopharyngeal carriage. Carriers were more likely to have had frequent otitis media episodes (P < .02) and otitis media not responsive to antimicrobial therapy (P < .001). Strategies to limit the spread of highly resistant pneumococcal strains should include encouraging judicious use of antimicrobic agents and reevaluating indications for prophylactic use of antimicrobic agents.

Topics: Adult; Age Factors; Carrier State; Child; Child Day Care Centers; Child, Preschool; Drug Resistance, Microbial; Erythromycin Ethylsuccinate; Humans; Infant; Nasopharynx; Ohio; Otitis Media; Penicillin Resistance; Pneumococcal Infections; Rifampin; Risk Factors; Streptococcus pneumoniae

Eighty-four isolates of penicillin-resistant pneumococci were tested for susceptibility to vancomycin, rifampicin, cotrimoxazole, and 14 beta-lactam antibiotics by agar and microbroth dilution methods. Twenty-three were from adult patients with pneumococcal disease, 57 from nasopharingeal carriers (preschool children) and four were resistant South African isolates. For all isolates tested, imipenem (N-formimidoyl thienamycin), rifampicin, ceftriaxone and cefotaxime had the greatest activity ( MIC90 : 0 X 12, 0 X 25, 0 X 5 mg/l, respectively). Cefoxitin and latamoxef were the least active of the drugs studied. The remaining beta-lactams tested had less activity than that of penicillin. All strains were inhibited by 1 mg/l of vancomycin and all but one were resistant to cotrimoxazole. The excellent in-vitro activities of the newer beta-lactam agents (ceftriaxone, cefotaxime and, particularly, imipenem ) and vancomycin against penicillin-resistant pneumococci offer a considerable promise for their use in the treatment of pneumococcal meningitis caused by these strains.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; beta-Lactams; Carrier State; Child; Drug Combinations; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Penicillin Resistance; Pneumococcal Infections; Rifampin; Streptococcus pneumoniae; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Topics: Animals; Bacteria; Bacterial Infections; Bordetella; Drug Evaluation, Preclinical; Enterococcus faecalis; Escherichia coli; In Vitro Techniques; Klebsiella pneumoniae; Listeria monocytogenes; Listeriosis; Mice; Microbial Sensitivity Tests; Pneumococcal Infections; Proteus Infections; Proteus mirabilis; Proteus vulgaris; Pseudomonas aeruginosa; Rifampin; Salmonella typhimurium; Sarcina; Staphylococcal Infections; Staphylococcus; Streptococcal Infections; Streptococcus; Streptococcus pneumoniae

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Chloramphenicol; Chlortetracycline; Dihydrostreptomycin Sulfate; Drug Stability; Erythromycin; Gastric Juice; Hydrogen-Ion Concentration; Kanamycin; Male; Mice; Microbial Sensitivity Tests; Novobiocin; Penicillin Resistance; Penicillins; Pneumococcal Infections; Rifampin; Solutions; Staphylococcal Infections; Staphylococcus; Streptococcal Infections

Topics: Animals; Cephaloridine; Escherichia coli; Escherichia coli Infections; Infections; Klebsiella; Klebsiella Infections; Listeria monocytogenes; Listeriosis; Mice; Pasteurella; Pasteurella Infections; Pneumococcal Infections; Rifampin; Salmonella Infections, Animal; Salmonella typhimurium; Staphylococcal Infections; Staphylococcus; Streptococcus pneumoniae

Topics: Chronic Disease; Humans; Infections; Nitrogen; Pneumococcal Infections; Respiratory Tract Infections; Rifampin; Staphylococcal Infections; Tuberculosis, Pulmonary; Urinary Tract Infections

Topics: Adolescent; Adult; Bone Diseases; Central Nervous System Diseases; Female; Humans; Injections, Spinal; Male; Middle Aged; Neurosurgery; Pneumococcal Infections; Rifampin; Skin Diseases; Staphylococcal Infections

Topics: Animals; Blood; Humans; In Vitro Techniques; Mice; Pneumococcal Infections; Rifampin; Staphylococcal Infections; Streptococcal Infections; Urine