Susceptibility testing interpretive criteria for levofloxacin when testing respiratory pathogens, Haemophilus influenzae and Moraxella catarrhalis

The more active L-isomer, levofloxacin, of the racemic ofloxacin mixture has been under development for therapeutic use. In this study, we evaluated the activity of ofloxacin, levofloxacin, and D-ofloxacin against the fastidious respiratory tract pathogens Haemophilus influenzae and Moraxella catarrhalis. Levofloxacin was two-fold more active than ofloxacin against H. influenzae (MIC90, 0.015 microgram/ml), and D-ofloxacin was least active (MIC90, 1 microgram/ml). For M. catarrhalis the MIC90 values were 0.03 microgram/ml, 0.06 microgram/ml, and 2 micrograms/ml for levofloxacin, ofloxacin, and D-ofloxacin, respectively. For disk diffusion susceptibility testing, Chocolate Mueller-Hinton agar (CMH) was considered preferable to Haemophilus test medium (HTM) because it supported the growth of all of 105 H. influenzae strains whereas five strains failed to grow on HTM. In addition, the margins of the zones of inhibition were more distinct on CMH and the Haemophilus species strains with elevated fluoroquinolone MICs were readily distinguished. The superior growth on CMH was reflected in a reduction of inhibition zone diameters of 2-3 mm relative to the inhibition zone diameters on HTM. The previously proposed interpretive criteria for the 5 microgram disk diffusion susceptibility test (susceptible at > or = 17 mm) results in complete categorical agreement with the reference microdilution broth method for M. catarrhalis on Mueller Hinton agar and for H. influenzae on HTM and CMH. However, the minimum diameter of the zone of inhibition recorded for a member of the dominant population of either species was considerably greater (25 mm) than 17 mm on any of the media tested.     

Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1996)

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In 16 institutions around the entire Japan, 557 strains of presumably etiological bacteria were isolated mainly from the sputa of 449 patients with lower respiratory tract infections during the period from October 1996 to September 1997. MICs of various antibacterial agents and antibiotics were determined against 98 strains of Staphylococcus aureus, 93 strains of Streptococcus pneumoniae, 84 strains of Haemophilus influenzae, 84 strains of Pseudomonas aeruginosa (non-mucoid strains), 17 strains of Pseudomonas aeruginosa (mucoid strains), 31 strains of Moraxella subgenus Branhamella catarrhalis, 21 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation. 1) S. aureus S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 67.3%. The frequency of the drug resistant bacteria increased comparing to the previous year's 52.7%. Arbekacin (ABK) and vancomycin (VCM) showed the highest activities against both S. aureus and MRSA with MIC80s of 1 microgram/ml. 2) S. pneumoniae Imipenem (IPM) and panipenem (PAPM) of carbapenems showed the most potent activities with MIC80s of 0.063 microgram/ml. Faropenem (FRPM) showed the next potent activity with MIC80 of 0.125 microgram/ml. The other drugs except erythromycin (EM), clindamycin (CLDM) and tetracycline (TC) were active against S. pneumoniae tested with MIC80s of 8 micrograms/ml or below. 3) H. influenzae The activities of all drugs were potent against H. influenzae tested with MIC80s of 4 micrograms/ml or below. Cefotiam (CTM), cefmenoxime (CMX), cefditoren (CDTR) and ofloxacin (OFLX) showed the most potent activities with MIC80s of 0.063 microgram/ml. 4) P. aeruginosa (mucoid strains) Tobramycin (TOB) showed the most potent activity against P. aeruginosa (mucoid strains) with MIC80 of 1 microgram/ml. Ceftazidime (CAZ), cefsulodin (CFS), IPM, gentamicin (GM), ABK and ciprofloxacin (CPFX) showed the next potent activities, with MIC80s of 2 micrograms/ml. The MIC80s of the other drugs ranged from 4 micrograms/ml to 16 micrograms/ml. 5) P. aeruginosa (non-mucoid strains) TOB and CPFX showed the most potent activities against P. aeruginosa (non-mucoid strains) with MIC80s of 1 microgram/ml. The MIC80s of piperacillin (PIPC) and cefoperazone (CPZ) were 16 micrograms/ml in 1995, and they were 64 micrograms/ml in 1996. 6) K. pneumoniae All drugs except ampicillin (ABPC) were active against K. pneumoniae. CMX, cefpirome (CPR), cefozopran (CZOP) and carumonam (CRMN) showed the most potent activities against K. pneumoniae with MIC80s of 0.125 microgram/ml. The MIC80s of the other drugs ranged from 0.25 microgram/ml to 2 micrograms/ml. 7) M.(B) catarrhalis Against M.(B.) catarrhalis, all drugs showed good activities with MICs of 4 micrograms/ml or below. IPM and minocycline (MINO) showed the most potent activities with MICs of 0.063 microgram/ml. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. Patients' backgrounds were examined for 557 isolates from 449 cases. The examination of age distribution indicated that the proportion of patients with ages over 60 years was 71.0% of all the patients showing a slight increase over that in 1994. Proportions of diagnosed diseases were as follows: Bacterial pneumonia and chronic bronchitis were the most frequent with 35.9% and 30.3% respectively. They were followed by bronchiectasis with a proportion of 10.     

Outpatient management of asthma during pregnancy

CS-834 is a prodrug of the carbapenem R-95867, developed by Sankyo Co., Ltd., Tokyo, Japan. To investigate the possibility that CS-834 may be the first carbapenem usable in an oral dosage form, its in vitro antibacterial activity (as R-95867) and in vivo antibacterial activity were compared with those of cefpodoxime proxetil, cefditoren pivoxil, cefdinir, ofloxacin, imipenem, and amoxicillin. R-95867 had high levels of activity against methicillin-susceptible staphylococci and streptococci, including penicillin-resistant Streptococcus pneumoniae, as well as Neisseria gonorrhoeae, Moraxella catarrhalis, the members of the family Enterobacteriaceae (with the exception of Serratia marcescens), Haemophilus influenzae, and Bordetella pertussis; for all these strains, the MICs at which 90% of tested strains are inhibited (MIC90s) were 1.0 microg/ml or less. Against methicillin-resistant staphylococci, enterococci, Serratia marcescens, Burkholderia cepacia, Stenotrophomonas maltophilia, and Acinetobacter calcoaceticus, R-95867 showed activity comparable to or slightly less than that of imipenem, with MIC90s ranging from 2 to >128 microg/ml. The in vivo efficacy of oral CS-834 against experimental mouse septicemia caused by gram-positive and gram-negative bacteria was better than that of comparative drugs. In murine respiratory infection models, the efficacy of CS-834 reflected not only its potent in vitro activity but also the high levels present in the lungs.     

Antimicrobial activity of RU-66647, a new ketolide

A new macrolide subclass called ketolides, possess a mode of action similar to the macrolide-lincosamide-streptogramin (MLS) compounds. Utilizing reference in vitro tests, the in vitro activity of RU-66647 (a ketolide) was compared to other MLS compounds against 376 Gram-positive organisms and over 400 representative strains of Gram-negative bacilli. The ketolide's spectrum was most similar to clindamycin and an earlier drug in the series (RU-64004 or RU-004) against staphylococci and streptococci. However, RU-66647 was more active than erythromycin and azithromycin against oxacillin-resistant Staphylococcus spp. and vancomycin-resistant enterococci. Ketolide activity was more potent than other MLS drugs against vancomycin-susceptible enterococci (MIC90, 0.25-4 micrograms/ml) and all streptococci (MICs, < or = 0.25 microgram/ml). Erythromycin-resistant (constitutive) strains were generally inhibited by < or = 2 micrograms RU-66647/ml (staphylococci, 31 to 36%; streptococci, 100%; enterococci, 72%). RU-66647 was active against Haemophilus influenzae (MIC90, 2 micrograms/ml), Moraxella catarrhalis (MIC90, 0.12 microgram/ml), and pathogenic Neisseria spp. (MIC90 0.5 microgram/ml). The ketolide failed to inhibit Enterobacteriaceae, nonfermentative Gram-negative bacilli, and Bacteriodes fragilis group strains. RU-66647 was observed to be a promising new compound directed toward some organisms resistant to other MLS-class drugs.     

In vitro and in vivo antibacterial activities of CS-834, a novel oral carbapenem

CS-834 is a novel oral carbapenem antibiotic. This compound is an ester-type prodrug of the active metabolite R-95867. The antibacterial activity of R-95867 was tested against 1,323 clinical isolates of 35 species and was compared with those of oral cephems, i.e., cefteram, cefpodoxime, cefdinir, and cefditoren, and that of a parenteral carbapenem, imipenem. R-95867 exhibited a broad spectrum of activity covering both gram-positive and -negative aerobes and anaerobes. Its activity was superior to those of the other compounds tested against most of the bacterial species tested. R-95867 showed potent antibacterial activity against clinically significant pathogens: methicillin-susceptible Staphylococcus aureus including ofloxacin-resistant strains, Streptococcus pneumoniae including penicillin-resistant strains, Clostridium perfringens, Neisseria spp., Moraxella catarrhalis, most members of the family Enterobacteriaceae, and Haemophilus influenzae (MIC at which 90% of strains are inhibited, < or =0.006 to 0.78 microg/ml). R-95867 was quite stable to hydrolysis by most of the beta-lactamases tested except the metallo-beta-lactamases from Stenotrophomonas maltophilia and Bacteroides fragilis. R-95867 showed potent bactericidal activity against S. aureus and Escherichia coli. Penicillin-binding proteins 1 and 4 of S. aureus and 1Bs, 2, 3, and 4 of E. coli had high affinities for R-95867. The in vivo efficacy of CS-834 was evaluated in murine systemic infections caused by 16 strains of gram-positive and -negative pathogens. The efficacy of CS-834 was in many cases superior to those of cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil, especially against infections caused by S. aureus, penicillin-resistant S. pneumoniae, E. coli, Citrobacter freundii, and Proteus vulgaris. Among the drugs tested, CS-834 showed the highest efficacy against experimental pneumonia in mice caused by penicillin-resistant S. pneumoniae.     

In vitro and in vivo antibacterial activities of ER-35786, a new antipseudomonal carbapenem

ER-35786 is a new parenteral 1 beta-methyl carbapenem with a broad antibacterial spectrum and a potent antipseudomonal activity. It showed high in vitro activity, comparable to those of meropenem and a new carbapenem, BO-2727, against methicillin-susceptible Staphylococcus aureus and streptococci, with MICs at which 90% of strains tested are inhibited (MIC90S) of < or = 0.39 microgram/ml. Against methicillin-resistant S. aureus, ER-35786 was the most active among the compounds tested, yet its MIC90 was 12.5 micrograms/ml. Against members of the family Enterobacteriaceae, Moraxella catarrhalis, and Haemophilus influenzae, ER-35786 inhibited 90% of strains tested at a concentration of < or = 1.56 micrograms/ml. The MIC90 of ER-35786 for Pseudomonas aeruginosa was 3.13 micrograms/ml, and the compound was more active than meropenem. In addition, the activity of ER-35786 against imipenem-, meropenem-, cefclidin-, or ceftazidime-resistant P. aeruginosa was equal to or higher than that of the most active reference compound. The in vivo activity of ER-35786 was consistent with this in vitro activity. The in vivo activity of ER-35786 was highest for systemic infection models with methicillin-resistant S. aureus and beta-lactam-resistant P. aeruginosa strains. In acute pneumonia caused by P. aeruginosa, ER-35786 produced a greater reduction in the viable cell count in the lungs than did imipenem-cilastatin or meropenem.     

Recent trends in incidence of respiratory tract pathogens and antimicrobial susceptibilities of Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis isolated in 1994 and 1995

The incidence of pathogenic bacteria in respiratory tract infections in 1994 and 1995 was investigated using quantitative cultures of sputa from patients with the infections in our department. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis were isolated at high rates (70.5% in 1994 and 73.8% in 1995) from the specimens of out-patients, and the incident rates were similar to the past data. The antimicrobial susceptibilities of these three pathogens were examined with the agar dilution method. The incidence of penicillin (Pc) resistant S. pneumoniae against which MIC of Pc-G was higher than 0.125 microgram/ml was markedly increased from 24% in 1994 to 34.9% in 1995. Most of the Pc resistant isolates were also resistant to other antibiotics including erythromycin, minocycline and tosufloxacin. Serotype of strains against which MIC of Pc-G was higher than 1.0 microgram/ml was 19. The ratios of beta-lactamase-producing strains among H. influenzae isolated in 1994 and 1995 were 20 and 15.8%, respectively, which were slightly higher than those in the past. One quinolone resistant strain was isolated in this study. Although the ratio of beta-lactamase-producing strains among M. catarrhalis was as high (96.7%) as in the past, no increased resistance against the drugs examined was observed.     

Decreased nitrogen rates and irrigation effect on celery yield and internal quality

Sparfloxacin, a new orally administered fluoroquinolone, was tested against 14,182 clinical strains isolated (generally blood stream and respiratory tract cultures) at nearly 200 hospitals in the United States (USA) and Canada. Sparfloxacin activity was compared with 13 other compounds by Etest (AB BIODISK, Solna, Sweden), broth microdilution, or a standardized disk diffusion method. Using the Food and Drug Administration/product package insert MIC breakpoint for sparfloxacin susceptibility (< or = 0.5 microgram/ml), 94% of Streptococcus pneumoniae (2666 isolates) and 89% of the other streptococci (554 isolates) were susceptible. However, at < or = 1 microgram/ml (the breakpoint for all nonstreptococcal species) sparfloxacin susceptibility rates increased to 100% and 98%, respectively, for the two groups of streptococci. Only 50% and 65% of pneumococci were susceptible to ciprofloxacin (MIC90, 3 micrograms/ml) and penicillin (MIC90, 1.5 micrograms/ml), respectively. Although there were significant differences between regions in the USA in the frequency of penicillin-resistant pneumococcal strains, results indicate that the overall sparfloxacin MIC90 was uniformly at 0.5 microgram/ml. Nearly all (> or = 99%) Haemophilus species and Moraxella catarrhalis, including those harboring beta-lactamases, were susceptible to sparfloxacin, ciprofloxacin, and amoxicillin/clavulanic acid. Only cefprozil and macrolides demonstrated lower potency and spectrum against these two species. Sparfloxacin was active against oxacillin-susceptible Staphylococcus aureus (96 to 97%), Klebsiella spp. (95%), and other tested enteric bacilli (93%). Comparison between broth microdilution MIC and disk diffusion interpretive results for M. catarrhalis, Staphylococcus aureus, and the Enterobacteriaceae showed an absolute intermethod categorical agreement of > 95% using current sparfloxacin breakpoints, in contrast to those of cefpodoxime for S. aureus where a conspicuous discord (98% versus 59%) between methods was discovered. These results demonstrate that sparfloxacin possesses sufficient in vitro activity and spectrum versus pathogens that cause respiratory tract infections (indications), especially strains resistant to other drug classes such as the earlier fluoroquinolones, oral cephalosporins, macrolides, and amoxicillin/clavulanic acid. The sparfloxacin susceptibility breakpoint for streptococci may require modification (< or = 1 microgram/ml) based on the MIC population analysis presented here. A modal MIC (0.38 to 0.5 microgram/ml) was observed at the current breakpoint. Regardless, sparfloxacin inhibited 89% (nonpneumococcal Streptococcus spp.) to 100% (Haemophilus spp., M. catarrhalis) of the isolates tested with a median activity of 97% against indicated species.     

Criterion-related diagnostic validity and test-retest reliability of the MMPI-168(L) in mentally retarded adolescents and adults

The purpose of this study was to investigate the association of serum antibody levels to Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis with age, gender and smoking in an elderly population. The study population comprised all the inhabitants aged 65 years or over in a rural municipality in south-western Finland. Serum samples were obtained from 1,174 out of a total of 1,360 subjects. Bacterial antibodies were measured by enzyme immunoassay (EIA) using pneumolysin and whole bacterial cells of H. influenzae and M. catarrhalis (mixture of 10 different strains for both) as antigens. The main findings were as follows: (i) antibody levels generally decreased with increasing age both in men and in women; (ii) antibody titres against H. influenzae and M. catarrhalis were higher in men than in women; and (iii) antibody titres to H. influenzae and M. catarrhalis, but not to S. pneumoniae, were significantly higher in smokers than in non-smokers. These data suggest that antibody-mediated protection against respiratory pathogens may be impaired in the elderly, leading to a higher susceptibility to respiratory tract infections, that the exposure to H. influenzae and M. catarrhalis may be higher in men than in women, and that smokers have more respiratory infections or colonization due to these 2 bacteria than do non-smokers.     

Prevalence of antimicrobial-resistant pathogens in middle ear fluid: multinational study of 917 children with acute otitis media

The management of acute otitis media is complicated by the emergence of resistance to beta-lactam and other antibiotics among common pathogens. We conducted a large, international study of infants and children with acute otitis media to identify pathogens and susceptibility patterns. During the winter of 1994 to 1995, middle ear fluid samples were collected from 917 patients with acute otitis media in Bulgaria, the Czech Republic, Hungary, Romania, Slovakia, Israel, and the United States. A single reference laboratory performed in vitro susceptibility testing. Pathogens were isolated from 62% of the patients. For Streptococcus pneumoniae (30% of the patients), untypeable Haemophilus influenzae (17%), and Moraxella catarrhalis (4%), there was significant variation among geographic regions (P < 0.001). The composite susceptibilities of these three organisms to amoxicillin ranged from 62% in the United States to 89% in Eastern and Central Europe; the corresponding susceptibilities to amoxicillin-clavulanate ranged from 90% in Israel to 95% in Eastern and Central Europe. beta-Lactamase was produced by 31 and 100% of the isolates of H. influenzae and M. catarrhalis, respectively. More isolates of S. pneumoniae were susceptible to amoxicillin (90%) or amoxicillin-clavulanate (90%) than to penicillin (70%; P = 0.002). The prevalence of resistant S. pneumoniae was highest in patients less than 12 months of age. S. pneumoniae, H. influenzae, and M. catarrhalis remain the most important bacterial pathogens in patients with acute otitis media; however, their prevalence is variable and resistance patterns are changing.     

Relationship between nasopharyngeal colonization and the development of otitis media in children. Tonawanda/Williamsville Pediatrics

Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis are the predominant bacteria associated with otitis media. A cohort of 306 infants was followed from birth through 12 months to determine frequency and duration of colonization and risk of acute otitis media (AOM) and otitis media with effusion (OME). M. catarrhalis was the most common bacterium isolated. Infants colonized at < or = 3 months of age were at increased risk of AOM and OME. Early colonization with M. catarrhalis revealed the greatest risk (relative risk [RR] = 1.24), especially for OME (RR = 1.57). There was a strong relationship between the frequency of colonization and OM (r = .37, P < .001,) for each pathogen. Although S. pneumoniae, nontypeable H. influenzae, and M. catarrhalis are part of the normal nasopharyngeal flora during infancy, an increased rate of colonization may identify a subpopulation of children that is at increased risk of OM.     

Clinical study on azithromycin in 10% fine granules and 100mg capsules in the field of pediatrics

Azithromycin (AZM), a new oral macrolide antibiotic, in 10% fine granules or 100 mg capsules was given to pediatric patients to treat various infections. The following results were obtained in our studies of AZM for its antibacterial activities against clinical isolates, its pharmacokinetics, its efficacy, and its safety. 1. MICs of AZM, erythromycin (EM) and clarithromycin (CAM) were determined against a total of 57 strains all at 10(6) cfu/ml. Among Gram-positive cocci, MICs of AZM ranged from 0.78 to > 100 micrograms/ml against Staphylococcus aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes (11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus pneumoniae (10 strains). These MICs were similar to those of the other macrolides. Among Gram-negative bacilli, MICs of AZM were 0.05 micrograms/ml against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13 micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against salmonella sp. (1 strain). These values were similar to or lower than those of the other macrolides. Against Mycoplasma pneumoniae, MICs of AZM were < or = 0.0008 micrograms/ml in three strains. One strain of M. pneumoniae showed tolerance to AZM at MIC 25 micrograms/ml. The other agents exhibited higher MIC than AZM against this organism. 2. Plasma samples were collected from five patients receiving fine granules and four patients receiving capsules for drug level determination. The patients received AZM at 10.0 approximately 16.3 mg/kg body weight once daily for 3 days. Drug concentrations in plasma at two hours after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules. 3. Urine samples were collected from four patients receiving fine granules and four patients receiving capsules. Drug levels were determined to be 3 micrograms/ml at post-treatment 48 hours for fine granules and post-treatment 72 hours for capsules. Urinary excretion rates of AZM in three patients on capsules lied in a range between 4.69 and 10.17%. 4. Effectiveness of AZM in fine granules was evaluated in 128 patients having a total of 19 different infections. AZM was rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6, resulting in an efficacy rate of 89.1%. Effectiveness of AZM in capsular form was evaluated in 23 patients with five different infections. AZM was found "excellent" in 13 patients and "good" in 10, resulting in an efficacy rate of 100%. 5. AZM in fine granules eradicated 45 strains of 54 in 8 different bacteria. AZM in capsules eradicated 9 strains of 10 strains in 6 different bacteria. 6. As for adverse reactions, one patient complained of eruption, one vomiting, one loose stool, five diarrhea, when administered with fine granular form of AZM. One patient on AZM capsules experienced urticaria and vomiting. 7. As for abnormal laboratory changes, three patients were found with decreased WBC, seven with increased eosinophil, two with increased GOT and GPT, one with increased GPT. They were all on fine granular form of AZM. As far as abnormalities found in patients administered with AZM in capsular form, two showed decreased WBC, one decreased WBC along with increased eosinophil, and three increased eosinophil.     

The beta-lactamases of Moraxella (Branhamella) catarrhalis isolated from Danish children

Two distinct beta-lactamases have been isolated from Moraxella catarrhalis: the stronger acting BRO-1 enzyme and the weaker acting BRO-2. Several reports have noted an effect of penicillin and ampicillin on infections caused by M. catarrhalis in spite of the presence of beta-lactamase production. The purpose of this work was to charaterize the beta-lactamases of M. catarrhalis isolated from Danish children regarding type and susceptibility, and to relate these findings to the eradication of beta-lactamases-producing strains by use of antibiotic treatment with penicillin or ampicillin. MICs for penicillin V, ampicillin, cefuroxime and amoxicillin/clavulanic acid (2:1) were determined in 70 strains of M. catarrhalis: 46 strains from children with lower respiratory tract infection (LRTI) and 24 strains from respiratory healthy children, beta-lactamase production was found in 59 strains. The BRO-1 enzyme was identified by isoelectric focusing in 55 strains (93.2%) and BRO-2 in 3 strains (5.1%); in 1 strain no isoelectric bands were produced. All strains were susceptible to cefuroxime and amoxicillin/clavulanic acid, and non-beta-lactamase-producing strains were susceptible to penicillin and ampicillin. For the beta-lactamase-producing strains, MIC50 of penicillin was 8.0 micrograms/ml, while MIC50 of ampicillin was 1.0 microgram/ml and MIC90 of ampicillin was 2.0 micrograms/ml. M. catarrhalis was more often eradicated from the children who received antibiotic treatment with penicillin or ampicillin than from those who did not receive any treatment, indicating an in vivo effect of penicillin and ampicillin in spite of the beta-lactamase production.     

Lifetime use of alternative therapy: a study of Florida residents

OBJECTIVE: To determine the bacteriologic efficacy of ceftriaxone in nonresponsive acute otitis media in children. METHODS: In a prospective study 92 patients ages 3 to 36 months (median, 11 months) with culture-proved nonresponsive acute otitis media were studied from January, 1995, through August, 1997. The patients were treated with intramuscular ceftriaxone (50 mg/kg/l/day) for 3 days. Middle ear fluid was aspirated for culture by tympanocentesis on day of enrollment (Day 1); a second tap was performed on Days 4 to 10. Additional middle ear fluid cultures were obtained if clinical relapse occurred. Bacteriologic failure was defined by positive culture on Days 4 to 10. Patients were followed until Day 17+/-2. Susceptibility was measured by E test. RESULTS: The main drugs administered before enrollment were amoxicillin (38%), amoxicillinclavulanate (25%) and cefaclor (20%). Organisms recovered (n=105) were: Haemophilus influenzae, 54; Streptococcus pneumoniae, 47; Moraxella catarrhalis, 2; and Streptococcus pyogenes, 2. Thirty-four (72%) of the 47 S. pneumoniae isolates were intermediately resistant to penicillin (MIC 0.1 to 1.0 microg/ml), but all were susceptible to ceftriaxone (MIC < 0.5 microg/ml). Bacteriologic eradication was achieved in 100 of 105 (95%) cases: 54 of 54 (10O%) H. influenzae, 43 of 47 (92%) S. pneumoniae, 1 of 2 (50%) M. catarrhalis and 2 of 2 (100%) S. pyogenes. Bacteriologic success (with no relapse) occurred in 13 of 13 (100%) penicillin-susceptible S. pneumoniae vs. 28 of 34 (82%) S. pneumoniae intermediately resistant to penicillin (4 cases of bacteriologic failure and 2 cases of relapse). CONCLUSION: A 3-day intramuscular ceftriaxone regimen is efficacious for the treatment of nonresponsive acute otitis media. The optimal duration of treatment in cases of nonresponsive acute otitis media and whether ceftriaxone is efficacious for the treatment of nonresponsive otitis media caused by S. pneumoniae highly resistant to penicillin is yet to be determined.     

The microbiology of secretory otitis

The AA. realize a comparative study on the differences between the nasopharyngeal microbial flora of 50 children suffering a secretory otitis and other 40 children without middle ear disease. In nasopharyngeal cultures the pathogenic flora (Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Streptococcus beta hemoliticus group A, Staphilococcus aureus) amounted for 96 percent in children with secretory otitis, which figure was reduced to 80 percent in healthy infants (p < 0.05). Haemophilus influenzae was the most identified microorganism in a both nasopharyngeal and otic flora. We have found a significative association (p < 0.001) among nasopharyngeal and otic flora of each individual.     

Regulation of tissue plasminogen activator production in cultured human fetal mesangial cells

This study was designed to determine the persistence of culturable bacteria versus DNA in the presence of a middle ear effusion in a chinchilla model of otitis media. Cohorts of animals were either infected with an ampicillin-resistant Haemophilus influenzae strain or injected with a tripartite inoculum consisting of freeze-thawed Streptococcus pneumoniae; pasteurized Moraxella catarrhalis; and DNA from H influenzae. The H influenzae-infected animals displayed culture positivity and polymerase chain reaction positivity through day 35. In the chinchillas infected with the low-copy number inocula of S pneumoniae, DNA was not detectable after day 1 from the co-inoculated pasteurized M catarrhalis bacteria or the purified H influenzae DNA; however, amplifiable DNA from the live low-copy number bacteria persisted through day 21 even though they were not culture-positive past day 3. These results demonstrate that DNA, and DNA from intact but nonviable bacteria, does not persist in an amplifiable form for more than a day in the presence of an effusion; however, live bacteria, while not culturable, persist in a viable state for weeks.     

Nasopharyngeal colonization in Costa Rican children during the first year of life

BACKGROUND: The establishment of the nasopharyngeal flora was followed in Costa Rican children from birth to 1 year of age. METHODS: Nasopharyngeal cultures were obtained at 1 (n = 413), 3 (n = 393), 6 (n = 376) and 12 months (n = 356) of age from children representative of the population in the Puriscal district. Weekly cultures were obtained from a subcohort of these children (n = 101). Mother-infant diads (n = 95) and preschool children (n = 208) attending day-care centers were also studied. RESULTS: The estimated proportion of colonized children in the population differed markedly depending on the frequency of culture. Quarterly cultures showed a slow increase in carrier rates from 3.9% for Haemophilus influenzae, 3.1% for Streptococcus pneumoniae and 6.5% for Moraxella catarrhalis at 1 month of age to 10.1% carrying H. influenzae and 19.4% carrying S. pneumoniae by the end of the first year. By quarterly culture the proportion of children colonized at least once was 36% for S. pneumoniae, 26% for H. influenzae and 28% for M. catarrhalis. In contrast weekly sampling showed that 95 to 100% of the children were colonized at least once during the first year of life with H. influenzae, S. pneumoniae or M. catarrhalis. Nasopharyngeal carriage of H. influenzae, S. pneumoniae and M. catarrhalis was low in the mothers, and very few mother-infant pairs carried identical bacteria at the same time. In contrast carrier rates were high in the siblings attending day care (H. influenzae 27.9%, S. pneumoniae 39.4%, both organisms 26.6%). Infants with siblings had significantly higher bacterial carriage at all ages than infants without siblings. CONCLUSIONS: Quarterly nasopharyngeal cultures showed that Costa Rican infants acquire their nasopharyngeal flora at a rate comparable with that for infants in developed countries and that siblings are an important source of the bacteria. Weekly samplings showed that virtually all children were colonized at least once during the first year of life.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1995). I. Susceptibility distribution]

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 704 bacterial strains isolated from patients with urinary tract infections (UTIs) in 11 hospitals during the period of June 1995 to May 1996. Of the above bacterial isolates, Gram-positive bacteria accounted for 29.8% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 70.2% and most of them were Escherichia coli. Susceptibilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) and imipenem (IPM) showed the highest activities against E. faecalis isolated from patients with UTIs. The MIC90S of them were 1 microgram/ml. Vancomycin (VCM) and piperacillin (PIPC) were also active with the MIC90S of 2 micrograms/ml and 4 micrograms/ml, respectively. The others had low activities with the MIC90S of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM showed the highest activities against S. aureus isolated from patients with UTIs. Its MIC90 was 1 microgram/ml against both S. aureus and MRSA. Arbekacin (ABK) was also active with the MIC90 of 2 micrograms/ml. The other except minocycline (MINO) had very low activities with the MIC90S of 64 micrograms/ml or above. 3. Staphylococcus epidermidis ABK and MINO showed the strongest activities against S. epidermidis isolated from patients with UTIs. The MIC90S of them were 0.25 microgram/ml. VCM was also active with the MIC90 of 1 microgram/ml. The MIC90S of cephems ranged from 2 micrograms/ml to 16 micrograms/ml in 1994, but they ranged from 8 micrograms/ml to 128 micrograms/ml in 1995. These results indicated that some resistances existed among S. epidermidis to cephems. 4. Streptococcus agalactiae All drugs except gentamicin (GM) were active against S. agalactiae. ABPC, cefmenoxime (CMX), IPM, erythromycin (EM), clindamycin (CLDM) and clarithromycin (CAM) showed the highest activities. The MICs for all strains were lower than 0.125 microgram/ml. The MIC90S of the others were 2 micrograms/ml or below. 5. Citrobacter freundii IPM showed the highest activity against C. freundii isolated from patients UTIs. Its MIC90 was 1 microgram/ml. GM was also active with the MIC90 of 2 micrograms/ml. Cefpirome (CPR), cefozopran (CZOP) and amikacin (AMK) were also active with the MIC90S of 4 micrograms/ml. Penicillins and cephems except CMX, CPR and CZOP showed low activities with MIC90S of 256 micrograms/ml or above. 6. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 1 microgram/ml. MINO and tosufloxacin (TFLX) were also active with the MIC90S of 8 micrograms/ml. Penicillins and cephems except CPR and CZOP showed lower activities with the MIC90S of 256 micrograms/ml or above. 7. Escherichia coli. Most of the antimicrobial agents were active against E. coli. Particularly CPR, CZOP and IPM showed the highest activities against E. coli. The MICs for all strains were equal to or lower than 0.5 microgram/ml. CMX and TFLX were also active with the MIC90S of 0.125 microgram/ml or below. Penicillins were slightly active with MIC90S of 128 micrograms/ml or above. 8. Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except penicillins, with MIC90S of 2 micrograms/ml or below. Carumonam (CRMN) had the strongest activity against K. pneumoniae, the MICs for all strains were equal to or lower than 0.125 microgram/ml. Comparing with the result of 1994, the sensitivities of K. pneumoniae against all drugs had obviously changed into a better state. For example, the MIC90S of cephems ranged from 0.25 microgram/ml to 16 micrograms/ml in 1994, but they were all lower than 2 micrograms/ml in 1995. 9. Proteus mirabilis P. mirabilis was susceptible to a majority of drugs. CMX, ceftazidime (CAZ), cefixime (CFIX), and CRMN showed the highest activities against P. mirabilis isolated from patients with UTIs. MICs of CRMN for all     

Antimicrobial activity of fluoroquinolones and other antibiotics on 1,116 clinical gram-positive and gram-negative isolates

A total of 1,116 clinically isolated strains belonging to Staphylococcus aureus (200), Staphylococcus epidermidis (200), Streptococcus pneumoniae (20), Escherchia coli (200), Klebsiella spp. (177), Serratia marcescens (22), Pseudomonas aeruginosa (224), Haemophilus influenzae (35) and Salmonella (38) from the Department of Infectious Diseases, La Sapienza University in Rome (Italy) were tested against three fluoroquinolones (ofloxacin, ciprofloxacin and levofloxacin) and 10 other antibiotics (augmentin, ampicillin, cefaclor, cefixime, cefotaxime, cotrimoxazole, gentamicin, minocycline, oxacillin and vancomycin). Fluoroquinolones inhibited essentially about 100% of H. influenzae, Salmonella and S. pneumoniae, more than 75% of Staphylococcus including methicillin-resistant strains, and about 90% of Enterobacteriaceae and 50% of P. aeruginosa. Minimal inhibitory concentration values ranged from < 0.015 to > 32 micrograms/ml for Klebsiella, S. aureus and epidermidis, E. coli and P. aeruginosa; from < 0.015 to 2 micrograms/ml for Salmonella; from 0.03 to 16 micrograms/ml for Serratia; from < 0.015 to 1 microgram/ml for Haemophilus; and from 0.5 to 2 micrograms/ml for S. pneumoniae. Levofloxacin and to a lesser extent ofloxacin and ciprofloxacin, generally exhibited a greater activity than the other agents against both Gram-positive and Gram-negative bacteria. Regarding the distribution of resistant strains in Italy, we found a peculiar pattern of resistance as far as E. coli and P. aeruginosa were concerned. Quality control parameters are also summarized. S. epidermidis resulted as a new emergent pathogen especially in immunocompromised patients and its level of sensitivity has been modified over the last few years. In fact, the percentage of resistant strains to antibiotics or the percentage of methicillin-resistant isolates (in our study 35%), has gradually increased. Levofloxacin and ofloxacin showed good activity against staphylococcal strains compared with the majority of other antibiotics. These results suggest that the newer quinolones are promising antimicrobial agents for various infections.