trimethoprim--sulfamethoxazole-drug-combination and Haemophilus-Infections

Haemophilus influenzae is a relevant cause of morbidity and mortality among children under 5 years of age in the developing world. In Latin America, H. influenzae type b (Hib) conjugate vaccine and surveillance of H. influenzae antimicrobial susceptibility have been implemented in recent years. We have undertaken a systematic review and a pooled analysis on H. influenzae antimicrobial resistance, including reports of 15 Latin America countries over a 10-year period (1990-2000). We have found that 450 (21.4%) of 2,100 invasive isolates were beta-lactamase producers compared to 145 (14.5%) of 998 isolates of noninvasive isolates (p < 0.05). Ampicillin resistance was detected among 783 (21.9%) of 3,577 invasive isolates compared to 111 (17.2%) of 646 noninvasive strains (p < 0.05). In contrast, 568 (41.9%) of 1,355 noninvasive strains were trimethoprim-sulfamethoxazole (TMP-SMX) resistance against 241 (26.9%) of 897 invasive ones (p < 0.05). Therefore, TMP-SMX resistance was more common in nonsterile fluids than in sterile fluids. Over time, rates of beta-lactamase-producing strains were stable in Brazil and Mexico, whereas rates of TMP-SMX resistance were increasing in Brazil. It is predictable that following the Hib immunization, Latin America countries will be faced with increased nontypeable H. influenzae infection. Although standing by the nontypeable H. influenzae vaccine, in this novel epidemiological scenario of post-Hib vaccination in Latin America settings there is a need to improve H. influenzae resistance monitoring to guide clinicians to choose efficacious antimicrobial therapy.

Topics: beta-Lactamases; Data Interpretation, Statistical; Drug Resistance; Haemophilus Infections; Haemophilus influenzae; Humans; Latin America; Respiratory Tract Infections; Trimethoprim, Sulfamethoxazole Drug Combination

The last decade is characterized by the increase in antibiotic resistance among respiratory bacterial pathogens in the presence of only modest progress in the development of new antibacterial agents to overcome this resistance. A series of recent studies show clearly that the increased resistance among the main AOM pathogens (namely Streptococcus pneumoniae and Haemophilus influenzae) is associated with a dramatic decrease in bacteriologic response to antibiotic treatment, which in turn has an impact on clinical response. Thus, the individual patient is affected by the increasing antibiotic resistance. Moreover, the society as a whole is now also affected because the carriage and spread of antibiotic resistant AOM pathogens is remarkably impacted by antibiotic treatment. New studies show the remarkable ability of antibiotics to rapidly promote nasopharyngeal carriage and spread of antibiotic-resistant AOM pathogens. In these studies, the increase in carriage of antibiotic resistant S. pneumoniae is shown already after 3-4 days from initiation of antibiotic treatment and may last for weeks to months after treatment. Children carrying antibiotic-resistant organisms transmit those organisms to their family and to their day care centers and thus a vicious cycle is created in which increased antibiotic resistance with decreased response leads to increased antibiotic use, which in turn leads to further increase in resistance. New antibiotics are not likely to improve this situation. It is clear that the challenge in the next decade is to prevent AOM rather than to treat it. Efforts to prevent AOM include improved environmental factors, immunization with bacterial and viral vaccines and some creative measures such as prevention of colonization and attachment to epithelium of AOM pathogens. Whether these efforts will prove successful or, even if successful, will only modify the clinical and bacteriologic picture presenting new challenges, only time will tell.

Topics: Anti-Bacterial Agents; Bacterial Adhesion; Carrier State; Child; Child, Preschool; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Utilization; Environment; Haemophilus Infections; Haemophilus influenzae; Haemophilus Vaccines; Humans; Infant; Nasopharynx; Otitis Media; Pneumococcal Infections; Retrospective Studies; Streptococcal Vaccines; Streptococcus pneumoniae; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vaccination; Viral Vaccines

Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Chloramphenicol; Drug Combinations; Haemophilus Infections; Haemophilus influenzae; Humans; Infant, Newborn; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Vancomycin

This is a substudy of a larger randomized controlled trial on HIV-infected Zambian children, which revealed that cotrimoxazole prophylaxis reduced morbidity and mortality despite a background of high cotrimoxazole resistance. The impact of cotrimoxazole on the carriage and antibiotic resistance of Streptococcus pneumoniae and Haemophilus influenzae as major causes of childhood mortality in HIV-infected children was investigated since these are unclear. Representative nasopharyngeal swabs were taken prior to randomization for 181 of 534 children (92 on cotrimoxazole and 89 on placebo). Bacterial identification and antibiotic susceptibility were performed by routine methods. Due to reduced mortality, prophylactic cotrimoxazole increased the median time from randomization to the last specimen from 48 to 56 months (P = 0.001). The carriage of H. influenzae was unaltered by cotrimoxazole. Carriage of S. pneumoniae increased slightly in both arms but was not statistically significant in the placebo arm. In S. pneumoniae switching between carriage and no carriage in consecutive pairs of samples was unaffected by cotrimoxazole (P = 0.18) with a suggestion that the probability of remaining carriage free was lower (P = 0.10). In H. influenzae cotrimoxazole decreased switching from carriage to no carriage (P = 0.02). Cotrimoxazole resistance levels were higher in postbaseline samples in the cotrimoxazole arm than in the placebo arm (S. pneumoniae, P < 0.0001; H. influenzae, P = 0.005). Cotrimoxazole decreased switching from cotrimoxazole resistance to cotrimoxazole sensitivity in S. pneumoniae (P = 0.002) and reduced the chance of H. influenzae remaining cotrimoxazole sensitive (P = 0.05). No associations were observed between the percentage of CD4 (CD4%), the change in CD4% from baseline, child age at date of specimen, child gender, or sampling month with carriage of either pathogen.

Topics: Anti-Infective Agents; Child, Preschool; Drug Resistance, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae; HIV Infections; Humans; Male; Pneumococcal Infections; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; Zambia

A new chemotherapeutic drug oriprim was used for therapy of 36 patients with bronchopulmonary pathology. Its therapeutic efficacy was noted in 83.3% of the cases. In 6 patients oriprim therapy turned out to be ineffective as a result of early side-effects. The drug was effective in pneumococcal infection. In suspicion of anaerobic infection (B. fragilis, etc) oriprim was given in combination with metronidazole.

Topics: Administration, Oral; Bacterial Infections; Bronchitis; Clinical Trials as Topic; Drug Combinations; Enterobacteriaceae Infections; Haemophilus Infections; Haemophilus influenzae; Humans; Injections, Intramuscular; Pneumonia; Pneumonia, Pneumococcal; Pneumonia, Staphylococcal; Staphylococcus epidermidis; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

24 patients, admitted to hospital with lower respiratory tract infection, were treated with either co-trimoxazole (800 mg sulphamethoxazole + 160 mg trimethoprim) or trimethoprim (200 mg) orally twice daily. All showed a clinical improvement and with one exception respiratory pathogens were eliminated. Pharmacokinetics in blood, sputum and saliva were studied in 11 patients taking trimethoprim and 9 taking co-trimoxazole. No sulphamethoxazole was detected in either the sputum or saliva. Trimethoprim was found in higher concentrations in the sputum than in the blood, although there were wide and significant variations in individual patient's sputum pharmacokinetic profiles. Trimethoprim penetrates into the sputum at therapeutic concentrations in patients with chronic respiratory infections.

Topics: Adolescent; Adult; Aged; Drug Combinations; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Middle Aged; Respiratory Tract Infections; Saliva; Sputum; Staphylococcal Infections; Streptococcal Infections; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Non-typeable Haemophilus influenzae (NTHi) has become the major cause of invasive H. influenzae diseases in the post-H. influenzae type b vaccine era. The emergence of multidrug-resistant (MDR) NTHi is a growing public health problem. Herein, we investigated the molecular basis of MDR in NTHi. The isolated NTHi were subjected to antimicrobial susceptibility testing for 12 agents. Whole genome and plasmid sequencing were conducted and analyzed to identify significant genetic variations and plasmid-encoded genes conferred antibiotic resistance.. This study clarified the molecular epidemiology of MDR in NTHi. This can benefit the monitoring of drug resistance trends in NTHi and the adequate medical management of patients with NTHi infection.

Topics: Amoxicillin-Potassium Clavulanate Combination; Ampicillin; Anti-Bacterial Agents; Azithromycin; beta-Lactamases; Cefuroxime; Ciprofloxacin; Haemophilus Infections; Haemophilus influenzae; Humans; Levofloxacin; Microbial Sensitivity Tests; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Bacterial Agents; Azithromycin; Common Variable Immunodeficiency; Dihydropteroate Synthase; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Trimethoprim, Sulfamethoxazole Drug Combination

To compare the determinants of trimethoprim-sulfamethoxazole resistance with established susceptibility values for fastidious Haemophilus spp., to provide recommendations for optimal trimethoprim-sulfamethoxazole measurement.. We collected 50 strains each of Haemophilus influenzae and Haemophilus parainfluenzae at Bellvitge University Hospital. Trimethoprim-sulfamethoxazole susceptibility was tested by microdilution, E-test and disc diffusion using both Mueller-Hinton fastidious (MH-F) medium and Haemophilus test medium (HTM) following EUCAST and CLSI criteria, respectively. Mutations in folA, folP and additional determinants of resistance were identified in whole-genome-sequenced isolates.. Strains presented generally higher rates of trimethoprim-sulfamethoxazole resistance when grown on HTM than on MH-F, independent of the methodology used (average MIC 2.6-fold higher in H. influenzae and 1.2-fold higher in H. parainfluenzae). The main resistance-related determinants were as follows: I95L and F154S/V in folA; 3- and 15-bp insertions and substitutions in folP; acquisition of sul genes; and FolA overproduction potentially linked to mutations in -35 and -10 promoter motifs. Of note, 2 of 19 H. influenzae strains (10.5%) and 9 of 33 H. parainfluenzae strains (27.3%) with mutations and assigned as resistant by microdilution were inaccurately considered susceptible by disc diffusion. This misinterpretation was resolved by raising the clinical resistance breakpoint of the EUCAST guidelines to ≤30 mm.. Given the routine use of disc diffusion, a significant number of strains could potentially be miscategorized as susceptible to trimethoprim-sulfamethoxazole despite having resistance-related mutations. A simple modification to the current clinical resistance breakpoint given by the EUCAST guideline for MH-F ensures correct interpretation and correlation with the reference standard method of microdilution.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Culture Media; Drug Resistance, Multiple, Bacterial; Haemophilus Infections; Haemophilus influenzae; Haemophilus parainfluenzae; High-Throughput Nucleotide Sequencing; Humans; Microbial Sensitivity Tests; Mutation; Promoter Regions, Genetic; Trimethoprim, Sulfamethoxazole Drug Combination; Whole Genome Sequencing

Concern about Haemophilus influenzae infection has been increasing over recent decades. Given the emergence of H. influenzae with severe drug resistance, we assessed the prevalence of as well as risk factors and potential therapies for extensively drug-resistant (XDR) H. influenzae infection in Taiwan.. In total, 2091 H. influenzae isolates with disk diffusion-based antibiotic susceptibility testing from 2007 to 2018 were enrolled. H. influenzae strains resistant to ampicillin, chloramphenicol, levofloxacin, and trimethoprim-sulfamethoxazole tended to be isolated from patient wards (≧41%), whereas those resistant to amoxicillin-clavulanate, cefotaxime, and cefuroxime were more likely to be isolated from intensive care units (approximately 50%). XDR H. influenzae was first identified in 2007, and its incidence did not significantly change thereafter. Overall prevalence of single, multiple, and extensively drug-resistant H. influenzae over 2007-2018 was 21.5% (n = 450), 26.6% (n = 557), and 2.5% (n = 52), respectively. A stepwise logistic regression analysis revealed that blood culture (odds ratio: 4.069, 95% confidence intervals: 1.339-12.365, P = 0.013) was an independent risk factor for XDR H. influenzae infection. No nosocomial transmission of XDR H. influenzae observed. Antibiotic susceptibility testing results demonstrated that cefotaxime was effective against 78.8% (n = 41) of the XDR strains.. The presence of XDR H. influenzae strains was identified in Taiwan, and cefotaxime was efficacious against most of these strains.

Topics: Ampicillin; Anti-Bacterial Agents; Cefotaxime; Cefuroxime; Chloramphenicol; Cross Infection; Drug Resistance, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Incidence; Intensive Care Units; Levofloxacin; Logistic Models; Male; Microbial Sensitivity Tests; Taiwan; Trimethoprim, Sulfamethoxazole Drug Combination

Antibacterial treatment with cotrimoxazol (TxS), a combination of trimethoprim and sulfamethoxazole, generates resistance by, among others, acquisition of thymidine auxotrophy associated with mutations in the thymidylate synthase gene

Topics: A549 Cells; Animals; Anti-Bacterial Agents; Bacterial Proteins; Cell Line, Tumor; DNA, Bacterial; Drug Resistance, Microbial; Female; Genes, Bacterial; Haemophilus Infections; Haemophilus influenzae; Host-Pathogen Interactions; Humans; Interleukin-8; Lung; Mice; Microscopy, Electron, Transmission; Mutation; Respiratory Tract Infections; Spain; Sulfamethoxazole; Thymidine; Thymidylate Synthase; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Virulence

In the last few decades, co-trimoxazole (SXT), an antibacterial combination of trimethoprim and sulfamethoxazole, has been used for treatment of upper respiratory tract infection due to Haemophilus influenzae. The usage of this antibiotic has become less important due to emergence of SXT-resistant strains worldwide. Most reports associate SXT resistance to the presence of variants of dihydrofolate reductase (DHFR) dfrA genes which are responsible for trimethoprim resistance; while the sulfamethoxazole (SMX) resistance are due to sulfonamide (SUL) genes sul1 and sul2 and/or mutation in the chromosomal (folP) gene encoding dihydropteroate synthetase (DHPS). This study aims to detect and analyse the genes that are involved in SXT resistance in H. influenzae strains that were isolated in Malaysia. Primers targeting for variants of dfrA, fol and sul genes were used to amplify the genes in nine SXT-resistant strains. The products of amplification were sequenced and multiple alignments of the assembled sequences of the local strains were compared to the sequences of other H. influenzae strains in the Genbank. Of the five variants of the dhfA genes, dfrA1 was detected in three out of the nine strains. In contrast to intermediate strains, at least one variant of folP genes was detected in the resistant strains. Multiple nucleotide alignment of this gene revealed that strain H152 was genetically different from the others due to a 15-bp nucleotide insert in folP gene. The sequence of the insert was similar to the insert in folP of H. influenzae strain A12, a strain isolated in United Kingdom. None of the strains had sul1 gene but sul2 gene was detected in four strains. Preliminary study on the limited number of samples shows that the TMP resistance was attributed to mainly to dfrA1 and the SMX was due to folP genes. Presence of sul2 in addition to folP in seven strains apparently had increased their level of resistance. A strain that lacked sul1 or sul2 gene, its resistance to sulfonamide was attributed to a 15-bp DNA insert in the folP gene.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Dihydropteroate Synthase; DNA Primers; Drug Resistance, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Malaysia; Molecular Sequence Data; Mutation; Polymerase Chain Reaction; Sequence Analysis, DNA; Tetrahydrofolate Dehydrogenase; Trimethoprim, Sulfamethoxazole Drug Combination

The present study evaluates the feasibility of rapid surveillance of community antimicrobial resistance (AMR) patterns of Streptococcus pneumoniae and Haemophilus influenzae in India using nasopharyngeal swabs (NPSs) of school children. It compares the AMR data obtained with that of invasive and nasopharyngeal (NP) isolates studied previously. No one has done such surveillance since our study so we decided to publish and more clearly demonstrate the feasibility of the methodology we did.. This community-based, cross-sectional, cluster sample study had seven centers; each had two sites distant to them. Two hundred sixty school children per center were enrolled. NP swabbing was performed and isolates identified as S. pneumoniae and H. influenzae at each center were sent to reference laboratories.. From January to December 2004, 1,988 NP swabs were processed; 776 S. pneumoniae and 64 H. influenzae were isolated. The AMR patterns for S. pneumoniae to co-trimoxazole varied, with sensitivity as low as 6% in Mumbai, 29% in Chennai and Vellore, and 100% in Delhi and Lucknow. For H. influenzae, sensitivity rates to co-trimoxazole ranged from 22% to 62%. The AMR patterns for both bacteria in the present study with data from invasive and NP isolates studied earlier were similar.. The study demonstrates that it is practical and feasible to rapidly assess the AMR patterns of both S. pneumoniae and H. influenzae in NPSs of school children in different geographic locations all over India.

Topics: Anti-Bacterial Agents; Child; Cluster Analysis; Cross-Sectional Studies; Drug Resistance, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; India; Microbial Sensitivity Tests; Nasopharynx; Pneumococcal Infections; Population Surveillance; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination

Prior to the implementation of Haemophilus influenzae type b vaccination worldwide, H. influenzae has been one of the main causative agents of community acquired pneumonia and meningitis in children. Due to the lack of information on the characteristics of the H. influenzae isolates that have previously been collected in Malaysia, the H. influenzae were assessed of their microbial susceptibility to commonly used antibiotics. Emphasis was made on strains that were resistance to co-trimoxazole (SXT) and their mode of transfer of the antibiotic resistance determinants were examined. A collection of 34 H. influenzae isolates was serotyped and antimicrobial susceptibility tests were performed to 11 antibiotics. To the isolates that were found to be resistant to co-trimoxazole, minimum inhibition concentration (MIC) to SXT was performed using Etest while agar dilution method was used to measure the individual MICs of trimethoprim (TMP) and sulfamethoxazole (SUL). These isolates were also examined for presence of plasmid by PCR and isolation method. Conjugal transfers of SXT-resistant genes to SXT-susceptible hosts were performed to determine their rate of transfer. Result showed that 20.6% of the total number of isolates was serotype B while the remaining was non-typeable. Antimicrobial susceptibility profile of all the isolates revealed that 58.8% was resistant to at least one antibiotic. Majority of these isolates were equally resistant to ampicillin and tetracycline (29.4% each), followed by resistance to SXT (26.5%). From nine isolates that were found to be SXT-resistant, five contained plasmid/s. Conjugal transfer experiment showed that these five isolates with plasmid transferred SXT-resistance determinants at a higher frequency than those without. From these observations, it is postulated that plasmid is not involved in the transfer of SXT-resistance genes but presence of plasmid facilitates their transfer. The information obtained from this study provides some basic knowledge on the antimicrobial susceptibility pattern of the H. influenzae isolates and their mode of transfer of SXT-resistance genes.

Topics: Ampicillin; Anti-Bacterial Agents; Child; Community-Acquired Infections; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Haemophilus Infections; Haemophilus influenzae; Humans; Malaysia; Microbial Sensitivity Tests; Phenotype; Plasmids; Pneumonia, Bacterial; Serotyping; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Ampicillin; Anti-Bacterial Agents; Back Pain; Bacteremia; Diagnosis, Differential; Discitis; Haemophilus; Haemophilus Infections; Humans; Intervertebral Disc; Liver Cirrhosis; Magnetic Resonance Imaging; Male; Middle Aged; Osteomyelitis; Trimethoprim, Sulfamethoxazole Drug Combination

The association between trimethoprim-sulfamethoxazole use and resistance among the major respiratory tract pathogens was investigated by comparing regional consumption of the drug to regional resistance in the following year in 21 central hospital districts in Finland. A total of 23,530 Streptococcus pneumoniae isolates, 28,320 Haemophilus influenzae isolates, and 14,138 Moraxella catarrhalis isolates were tested for trimethoprim-sulfamethoxazole susceptibility during the study period (1998-2004). Among the S. pneumoniae isolates, a statistically significant connection was found between regional consumption and resistance. No statistically significant connection was found between regional trimethoprim-sulfamethoxazole use and resistance among H. influenzae and M. catarrhalis isolates. According to our results, it seems that only in pneumococci can the development of trimethoprim-sulfamethoxazole resistance be influenced by restricting its use. However, trimethoprim-sulfamethoxazole remains an important antimicrobial agent because of its reasonable price. Hence, resistance to trimethoprim-sulfamethoxazole among these pathogens needs continuous monitoring.

Topics: Drug Resistance, Bacterial; Finland; Haemophilus Infections; Haemophilus influenzae; Humans; Moraxella catarrhalis; Moraxellaceae Infections; Pneumonia, Pneumococcal; Respiratory Tract Infections; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination

Str. pneumoniae isolates were susceptible to penicillin, all to also ofloxacin and chloramphenicol and cefotaxim and 39 (100%) to cotrimoxazol. Concerning S. aureus, all isolates 22 were susceptible to oxacillin and chloramphenicol, and 21 also to cotrimoxazol. All N. meningitidis isolates but one-10 of all were susceptible to penicillin, all to cefotaxim, chloramphenicol and cotrimoxazol. All H.influenzae isolates were susceptible to ampicillin and chloramphenicol, as well as to ofloxacin and cotrimoxazol. Those surprisingly high susceptibilities to rather "old" antibiotics may be explained by low antibiotic consumption, accessibility and therefore low usage which is a key promoter of resistance both in community and hospital.

Topics: Anti-Bacterial Agents; Cefotaxime; Chloramphenicol; Drug Resistance, Microbial; Haemophilus Infections; Haemophilus influenzae; Humans; Meningitis, Bacterial; Microbial Sensitivity Tests; Neisseria meningitidis; Ofloxacin; Penicillins; Staphylococcal Infections; Staphylococcus aureus; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the carriage rate of Streptococcus pneumoniae and Haemophilus influenzae in healthy Indian schoolchildren. The prevalence of antibiotic resistant strains in the community may be used to assess the trends of antibiotic resistance in invasive strains. Prevalence of resistance to various antimicrobial drugs among S. pneumoniae and H. influenzae was estimated.. Two thousand four hundred subjects, aged 5-10 years, were enrolled from 45 rural and 45 urban schools. A nasopharyngeal swab was collected from each child, after taking informed written consent. Swabs were processed to isolate S. pneumoniae and H. influenzae. All isolates were tested for resistance to chloramphenicol, erythromycin and co-trimoxazole. Streptococcus pneumoniae isolates were also tested against tetracycline and oxacillin while H. influenzae isolates were tested against ampicillin.. Nasopharyngeal carriage of S. pneumoniae and H. influenzae was high in healthy schoolchildren. Stratified analysis showed that nasal carriage of pneumococci in urban children was significantly lower than in rural children [46.8% vs. 53.2%, P<0.001]. Carriage rates of H. influenzae in male and female populations were significantly different (47.8% vs. 52.3%, P<0.04). Penicillin resistance in S. pneumoniae was found low (3.3%), but 22.9% of H. influenzae isolates were ampicillin resistant. Resistance to co-trimoxazole was very high in both S. pneumoniae (81.8%) and H. influenzae (67.3%).. There is high nasopharyngeal carriage of drug resistant S. pneumoniae and H. influenzae in schoolchildren of north India. Currently, in India, co-trimoxazole for 5 days is recommended for treatment of non-severe pneumonia and third generation cephalosporins are drug of choice for management of severe pneumococcal/H. influenzae diseases. We found high co-trimoxazole resistance and low penicillin resistance in pneumococcal isolates. This justifies empirical use of penicillin in management of invasive pneumococcal infections in India.

Topics: Carrier State; Child; Child, Preschool; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Female; Haemophilus Infections; Haemophilus influenzae; Humans; India; Male; Nasopharynx; Penicillin Resistance; Pneumococcal Infections; Rural Health; Specimen Handling; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; Urban Health

Among respiratory tract isolates of Streptococcus pneumoniae from children, resistance to penicillins, cephalosporins, macrolides, and trimethoprim-sulfamethoxazole (SXT) increases on an annual basis. Pediatric patients who do not respond to conventional therapy for respiratory tract infections someday may be treated with fluoroquinolones. In this study, MICs of beta-lactams, azithromycin, SXT, and levofloxacin were determined and interpreted by using NCCLS guidelines for isolates of S. pneumoniae (2,834 from children and 10,966 from adults), Haemophilus influenzae (629 from children and 2,281 from adults), and Moraxella catarrhalis (389 from children and 1,357 from adults) collected during the 2000-2001 and 2001-2002 respiratory illness seasons in the United States as part of the ongoing TRUST surveillance studies. Rates of resistance to penicillin, azithromycin, and SXT were > or = 7.5% higher among patients < or = 4 years old than among patients 5 to 10, 11 to 17, and > or = 18 years old in both the 2000-2001 and the 2001-2002 respiratory illness seasons. Levofloxacin resistance was detected in 2 of 2,834 isolates (0.07%) from patients <18 years old. Levofloxacin MICs of 0.25 to 1 micro g/ml accounted for 99.6, 99.5, 99.3, 99.7, 98.4, and 98.0% of isolates from patients < 2, 2 to 4, 5 to 10, 11 to 17, 18 to 64, and > 64 years old. Multidrug resistance was twice as common among patients < or = 4 years old (25.3%) as among patients 5 to 10 years old (13.7%), 11 to 17 years old (11.9%), 18 to 64 years old (12.1%), and > 64 years old (12.4%). The most common multidrug resistance phenotype in S. pneumoniae isolates for all age groups was resistance to penicillin, azithromycin, and SXT (70.3 to 76.6%). For H. influenzae and M. catarrhalis isolates from patients < 2, 2 to 4, 5 to 10, 11 to 17, 18 to 64, and > 64 years old, levofloxacin MICs at which 90% of the isolates were inhibited were 0.015 and 0.03 to 0.06 microg/ml, respectively, in the 2000-2001 and 2001-2002 respiratory illness seasons. In the 2000-2001 and 2001-2002 respiratory illness season surveillance studies in the United States, 99.9% of pediatric isolates of S. pneumoniae were susceptible to levofloxacin. If fluoroquinolones become a treatment option for pediatric patients, careful monitoring of fluoroquinolone susceptibilities will be increasingly important in future surveillance studies.

Topics: Adolescent; Adult; Aged; Anti-Infective Agents; Azithromycin; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Lactams; Levofloxacin; Microbial Sensitivity Tests; Middle Aged; Moraxella catarrhalis; Ofloxacin; Pneumococcal Infections; Prospective Studies; Respiratory Tract Infections; Streptococcus pneumoniae; Trimethoprim, Sulfamethoxazole Drug Combination; United States

The Pakistan program for control of acute respiratory tract infections (ARIs) adopted the standard ARI-case-management strategy of the World Health Organization and recommended co-trimoxazole for the management of nonsevere pneumonia. Reports in that country of high in vitro antimicrobial resistance of Streptococcus pneumoniae and Haemophilus influenzae to co-trimoxazole prompted the program to reevaluate its treatment policy. Two community-based studies during 1991-1993 showed in vivo efficacy of co-trimoxazole in 92% and 91% of children with nonsevere pneumonia. A third double-blind trial showed co-trimoxazole and oral amoxicillin to be equally effective in vivo in cases of nonsevere pneumonia, despite high in vitro resistance. Country-wide surveillance from 1991 to 1994 revealed 78.3%-79.9% in vitro resistance to co-trimoxazole among S. pneumoniae isolates and 59.5%-61.0% among H. influenzae isolates. Co-trimoxazole is still recommended by the Pakistan ARI control program. The fact that amoxicillin is three times more expensive and must be administered more frequently is a big impediment to recommending it as a first-line drug for nonsevere pneumonia.

Topics: Acute Disease; Anti-Bacterial Agents; Developing Countries; Drug Resistance, Microbial; Haemophilus Infections; Haemophilus influenzae; Humans; Pakistan; Pneumococcal Infections; Respiratory Tract Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Treatment of childhood pneumonia in developing countries requires knowledge of susceptibility patterns for Streptococcus pneumoniae and Haemophilus influenzae. Between October 1991 and April 1993, a surveillance survey of antimicrobial resistance was performed at two fever hospitals in Egypt; nasopharyngeal swab and blood specimens obtained from 1,635 children with pneumonia were cultured for these organisms. Susceptibility testing of these organisms was performed. At least one of these organisms was isolated from nasopharyngeal swab specimens from 73% of the children; 3.7% of blood cultures were positive. For S. pneumoniae strains, 70.9% of nasopharyngeal isolates were calculated to be susceptible to penicillin vs. 77.6% of blood isolates; the percentages of isolates susceptible to co-trimoxazole were 73.0% and 75.0%, respectively. For H. influenzae strains, 93.0% of nasopharyngeal isolates were calculated to be susceptible to ampicillin vs. 100% of blood isolates; the percentages of isolates susceptible to co-trimoxazole were 84.9% and 100%, respectively. Although most S. pneumoniae and H. influenzae strains associated with childhood pneumonia in Cairo were susceptible to penicillins and co-trimoxazole, antimicrobial resistance did not occur.

Topics: Ampicillin; Ampicillin Resistance; Child, Preschool; Chloramphenicol; Chloramphenicol Resistance; Egypt; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Pneumococcal Infections; Pneumonia; Streptococcus pneumoniae; Trimethoprim Resistance; Trimethoprim, Sulfamethoxazole Drug Combination

Resistance patterns of S. pneumoniae and H. influenzae to standard antibiotics in Thailand is not on the rise when compared to previous reports. There is no need at present to change standard antibiotic therapy recommendations for pneumonia by the National ARI. The use of antibiotics for the treatment or prophylactic purposes should be judicious to limit the spread of antimicrobial resistance. This study is the main part of a National surveillance for antimicrobial resistance of S. pneumoniae and H. influenzae. The surveillance programme should be continued to evaluate trends in order to up-date guidelines for the selection of antibiotics of the ARI programme in the future.

Topics: Ampicillin; Anti-Bacterial Agents; Child, Preschool; Chloramphenicol; Drug Resistance, Microbial; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Penicillins; Respiratory Tract Infections; Streptococcal Infections; Streptococcus pneumoniae; Thailand; Trimethoprim, Sulfamethoxazole Drug Combination

A young woman with a history of sick sinus syndrome and placement of a permanent pacemaker 6 months before admission had fever and Haemophilus parainfluenzae bacteremia. A gallium scan localized the infection to the site of the pacemaker wire. Echocardiograms were negative for any vegetations. The patient responded to cefotaxime and trimethoprim-sulfamethoxazole therapy. We believe that this is the first case of H. parainfluenzae bacteremia associated with a pacemaker wire and localized by gallium scan.

Topics: Administration, Oral; Adolescent; Cefotaxime; Female; Gallium Radioisotopes; Haemophilus Infections; Humans; Infusions, Intravenous; Pacemaker, Artificial; Radionuclide Imaging; Sepsis; Sick Sinus Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination

In vitro activity of cefixime, an experimental oral third-generation cephalosporin and 7 other antimicrobials (ampicillin, augmentin, trimethoprim/sulfamethaxazole, cefamandole, cefotaxime, cefuroxime, and cefaclor) were determined for 150 isolates of Haemophilus obtained from pediatric patients. All (109) non-typeable H. influenzae isolates were sensitive to cefixime and cefotaxime. All (18) isolates of H. parainfluenzae were sensitive to cefotaxime, cefuroxime, cefamandole, cefaclor, and augmentin; 17/18 isolates were sensitive to cefixime. All (23) isolates of H. influenzae-b were sensitive to cefixime, cefotaxime, cefamandole, cefuroxime, cefaclor, and augmentin. Only 10/23 were sensitive to tri/sulfa. 137 of 150 (91.3%) isolates had MBCs equivalent to their MICs for cefixime, compared to 149/150 (99.3%) isolates for cefotaxime. Approximately 95% (143/150) of isolates tested had MICs of less than or equal to 0.06 microgram/ml for cefixime. These data demonstrate that in vitro cefixime has good activity against Haemophilus isolates and it is very similar to the activity of cefotaxime.

Topics: Anti-Bacterial Agents; Cefixime; Cefotaxime; Child; Drug Combinations; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Microbial Sensitivity Tests; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Single-dose therapy for selected genitourinary tract infections is an effective alternative to multiple-dose regimens. Candidal vulvovaginitis and trichomonal vaginitis may be routinely treated with single-dose regimens. With acute cystitis, candidates for single-dose therapy include patients who have a short duration of symptoms and are likely to comply with follow-up.

Topics: Acute Disease; Anti-Bacterial Agents; Antifungal Agents; Candidiasis, Vulvovaginal; Cystitis; Drug Administration Schedule; Drug Combinations; Female; Gardnerella vaginalis; Haemophilus Infections; Humans; Infections; Metronidazole; Sulfamethoxazole; Trichomonas Vaginitis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vaginal Diseases

From February 1981 to December 1983, 225 strains were isolated from pediatric patients infected with Haemophilus influenzae. Forty-one strains were found to be resistant to ampicillin, chloramphenicol, and other antibiotics. They were isolated from 20 patients with invasive diseases (meningitis, 16; bacteremia, 4) and 21 with noninvasive diseases (otitis media, 19; conjunctivitis, 2). During this period, 44 patients with invasive diseases were seen (meningitis, 28; bacteremia, 16). Strains resistant to both ampicillin and chloramphenicol occurred in 45.4% of cerebrospinal fluid and blood isolates and in 51% of cerebrospinal fluid isolates only. In this group, individual resistance to ampicillin was 50%; chloramphenicol, 52.2%; tetracycline, 54.5%; and sulfamethoxazole-trimethoprim, 63.6%. No epidemiological relationship could be found among the patients. The presence of asymptomatic carriers was investigated in two nurseries and in eight family groups. From a total of 125 individuals studied, 80 were found to be colonized by H. influenzae, and 36 carried multiply resistant strains. From patients and carriers, 77 strains were found to be resistant to ampicillin, chloramphenicol, and other drugs; 39 belonged to type b (cerebrospinal fluid, 16; blood, 4; ear, 7; and nasopharynx, 12), and 38 were non-type b. The most frequent pattern of resistance was ampicillin-chloramphenicol-tetracycline-sulfamethoxazole-trimethoprim (94.8%), followed by ampicillin-chloramphenicol-tetracycline (3.9%). The disk diffusion method correctly predicted multiple resistance. The mean inhibition zone diameters were: ampicillin, 12.8 mm; chloramphenicol, 15.2 mm; tetracycline, 9.9 mm; and sulfamethoxazole-trimethoprim, 10.8 mm. These resistant strains were susceptible to cefotaxime, moxalactam, cefoperazone, cefuroxime, rifampin, and gentamicin. Our data suggest that in Spain the resistance of H. influenzae to ampicillin and chloramphenicol is endemic and that other effective therapeutic modalities are needed.

Topics: Adult; Anti-Bacterial Agents; Carrier State; Child; Drug Combinations; Drug Resistance, Microbial; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Once a Hemophilus influenzae isolate is identified as the cause of a respiratory tract infection in an adult, it should be tested for beta-lactamase production, ie, for ampicillin resistance. The incidence of ampicillin-resistant strains of H influenzae is increasing. The Centers for Disease Control in Atlanta estimates an average incidence nationwide of 18% to 22%; the rate varies considerably from community to community. Thus, practitioners should be aware of the ampicillin-resistance rate in their community and should keep this rate in mind especially when treating patients empirically. Patients with H influenzae infections who are acutely ill, who fail to respond to ampicillin, or who are known to have an ampicillin-resistant infection on the basis of laboratory findings should receive therapy designed to combat ampicillin-resistant strains.

Topics: Adult; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; Bronchitis; Drug Combinations; Haemophilus Infections; Haemophilus influenzae; Humans; Penicillin Resistance; Pneumonia; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The increasing incidence of Haemophilus influenzae resistant to ampicillin has clinical implications not only for pediatricians but also for family physicians, because the bacterium is recognized more frequently as the etiologic agent for diseases in adults as well as in young children. Ampicillin is no longer the automatic choice for treatment of patients thought to have life-threatening H influenzae disease, and empiric treatment of otitis media must be reexamined. Chloramphenicol, as well as ampicillin, must be considered for the treatment of meningitis and other serious systemic H influenzae infections. Once the infective organism has been isolated and tested for resistance, ampicillin alone may be used if indicated or desired. Alternatives to ampicillin for middle ear infection are trimethoprim-sulfamethoxazole (Bactrim, Septra), erythromycin-sulfonamide (Pediazole), and cefaclor (Ceclor). Isolation and susceptibility tests are seldom done because they necessitate tympanocentesis.

Topics: Adult; Amoxicillin; Ampicillin; Anti-Bacterial Agents; Child; Chloramphenicol; Drug Combinations; Haemophilus Infections; Haemophilus influenzae; Humans; Meningitis, Haemophilus; Otitis Media; Penicillin Resistance; Pneumonia; Respiratory Tract Infections; Rifampin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

In vitro, Haemophilus influenzae strains have two distinct patterns of susceptibility to trimethoprim-sulfamethoxazole (TMP/SMZ); strains with low minimum inhibitory concentration and high minimum bactericidal concentration (tolerant) and those with both low minimum inhibitory concentration and minimum bactericidal concentration (kill-sensitive). Tolerant H. influenzae strains were found to elaborate significantly more type b capsular polysaccharide, a linear polymer of ribosyl ribose phosphate (PRP), than kill-sensitive strains. Tolerant strains became susceptible to killing by TMP/SMZ when type b capsule was physically removed, but reacquired tolerance following growth and reversion to original (mucoid) phenotype. Susceptibility of wild (type a, b, c), isogenic (type b and untypable), and transformed (type b and d) strains indicated that elaboration of type b capsule was associated with TMP/SMZ tolerance. In a second series of studies, virulence of H. influenzae in the infant rat model was correlated with in vitro tolerance. Tolerant strains (13/13) caused systemic disease while none (0/7) of kill-sensitive strains were pathogenic. The efficacy of TMP/SMZ in the treatment of invasive infection was evaluated in rats with established bacteremia and meningitis. TMP/SMZ failed to eradicate H. influenzae b from the blood in 85% (17/20) or from the cerebrospinal fluid in 95% (19/20) of infected animals. Thus, in vitro tolerance correlated with therapeutic failure in vivo.

Topics: Animals; Drug Combinations; Drug Resistance, Microbial; Drug Tolerance; Haemophilus Infections; Haemophilus influenzae; Humans; Polysaccharides, Bacterial; Rats; Rats, Inbred Strains; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination