Spontaneous intracranial hypotension: clinical and magnetic resonance imaging characteristics

OBJECTIVE: To evaluate the antimicrobial susceptibility pattern of oxacillin susceptible (OSSA) and resistant Staphylococcus aureus (ORSA) isolates to other antimicrobial agents that can be used for the treatment of staphylococcal infections. MATERIAL AND METHOD: We evaluated 117 clinical S. aureus isolates from several S?o Paulo hospitals. Clinical isolates from Campinas, SP and from Jo?o Pessoa, PB, were also included. The in vitro susceptibility testing was performed by broth microdilution as described by the National Committee for Clinical Laboratory Standards (NCCLS). The minimum inhibitory concentration (MIC) was evaluated for 24 antimicrobial agents, including beta-lactams, fluoroquinolones, aminoglycosides, glycopeptides, macrolides, lincosamides and streptogramins. Both commercially available and experimental drugs were included in the study. Cross-resistance among fluoroquinolones was evaluated by susceptibility testing 24 isolates to 10 fluoroquinolones. RESULTS: The antimicrobial agents that showed the highest in vitro activity were the glycopeptides, the streptogramin RP-59.500, and the mupirocin (100% susceptibility). Eighty-seven percent of the OSSA and only 38% of the ORSA isolates were susceptible to ciprofloxacin (MIC50 0.25 microgram/mL and > 4 micrograms/mL, respectively). Cross-resistance among fluoroquinolones were noted even for the experimental drugs. Two fluoroquinolones remained active against ciprofloxacin-resistant isolates, clinafloxacin and WIN-57.273. However, the ciprofloxacin-resistant isolates had MICs eight-to 64-fold higher than the ciprofloxacin-susceptible isolates, suggesting that the MICs may continue to increase when these fluoroquinolones become commercially available. CONCLUSION: Our results showed a high rate of antimicrobial resistance among S. aureus from the Brazilian hospitals. Very few drugs can still be used for the treatment of staphylococcal infections.     

Tissue water content in rats measured by desiccation

The in vitro activity of cefepime was compared to that of ceftazidime, ceftriaxone, and cefotaxime in a multicenter study involving 10 clinical microbiology laboratories and clinical isolates from 18 Brazilian hospitals from 7 cities (4 states). A total of 982 isolates consecutively collected between December 1995 and March 1996 were susceptibility tested by using Etest and following the NCCLS procedures for agar diffusion tests. The cefepime spectrum was broader than that of the other broad-spectrum cephalosporins against both Gram-negative rods and Gram-positive cocci. Cefepime was particularly more active against Enterobacter sp. (MIC90, 2 micrograms/ml), Serratia sp. (MIC90, 2 micrograms/ml) and oxacillin-susceptible Staphylococcus aureus (MIC90, 3 micrograms/ml). Against Pseudomonas aeruginosa, cefepime (MIC90, 16 micrograms/ml) was slightly more active than ceftazidime (MIC90, 32 micrograms/ml) and 8- to 16-fold more active than ceftriaxone of cefotaxime (MIC90, > 256 micrograms/ml). Our results show that nosocomial bacteria, especially Gram-negative rods, have a high rate of cephalosporin resistance in Brazil. However, part of these resistant bacteria remains susceptible to cefepime. The Etest was shown to be an excellent method for multicenter studies of the in vitro evaluation of new antimicrobial agents.     

Antimicrobial activity of quinupristin-dalfopristin (RP 59500, Synercid) tested against over 28,000 recent clinical isolates from 200 medical centers in the United States and Canada

A total of 200 medical center laboratories in the USA and Canada contributed results of testing quinupristin-dalfopristin, a streptogramin combination (formerly RP 59500 or Synercid), against 28,029 Gram-positive cocci. Standardized tests [disk diffusion, broth microdilution, Etest (AB BIODISK, Solna, Sweden)] were utilized and validated by concurrent quality control tests. Remarkable agreement was obtained between test method results for characterizing the collection by the important emerging resistances: 1) oxacillin resistance among Staphylococcus aureus (41.0 to 43.7%); 2) vancomycin resistance among Enterococcus faecium (50.0 to 52.0%); and 3) the penicillin nonsusceptible rate for pneumococci (31.1% overall, with 10.6% at MICs of > or = 2 micrograms/mL). The quinupristin-dalfopristin MIC90 for oxacillin-susceptible and -resistant S. aureus was 0.5 microgram/mL and 1 microgram/mL, respectively. The quinupristin-dalfopristin MIC90 for vancomycin-resistant E. faecium was 1 microgram/mL, and only 0.2% of isolates were resistant. Other Enterococcus species were generally not susceptible to the streptogramin combination but were usually inhibited by ampicillin (86 to 97% susceptible; MIC50, 1.0 microgram/mL) or vancomycin (86 to 95%; MIC50, 1.0 microgram/mL). Among all tested enterococci, the rate of vancomycin resistance was 16.2%. The quinupristin-dalfopristin MIC90 (0.75 microgram/mL) for 4,626 tested Streptococcus pneumoniae strains was not influenced by the penicillin or macrolide susceptibility patterns. When five regions in the USA and Canada were analyzed for significant streptogramin and other antimicrobial spectrum differences, only the Farwest region had lower numbers of streptogramin-susceptible E. faecium. Canadian strains were generally more susceptible to all drugs except chloramphenicol and doxycycline when tested against E. faecalis (73% and 89% susceptible, respectively). The U.S. Southeast region had S. pneumoniae strains less susceptible to macrolides (73%) but had more susceptibility among E. faecium isolates tested against vancomycin and ampicillin. The Northeast region of the USA had the greatest rate of vancomycin resistance among enterococci. Strains retested by the monitor because of quinupristin-dalfopristin resistance (MICs, > or = 4 micrograms/mL) were generally not confirmed (2.2% validation), and only 0.2% of E. faecium isolates were identified as truly resistant. The most common errors were: 1) species misidentification (28.0%); 2) incorrect susceptibility results (65.6%); and 3) mixed cultures (4.3%) tested by participants. Overall, quinupristin-dalfopristin was consistently active (> or = 90% susceptible) against major Gram-positive pathogens in North America, regardless of resistance patterns to other drug classes and geographic location of their isolation.     

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.     

The antimicrobial susceptibility of Mycobacterium chelonae isolated from corneal ulcer

PURPOSE: To determine the in vitro susceptibility of Mycobacterium chelonae isolates from corneal ulcers to various traditional and newly-developed antimicrobial agents, alone or in combination. METHODS: Fifteen strains of M. chelonae isolated from corneal ulcers were collected at the National Taiwan University Hospital from 1989 to 1993. Susceptibility to antimicrobial agents was tested by the broth microdilution method to determine the minimum inhibitory concentration (MIC). The antimicrobial effects of combinations of antimicrobial agents were assessed by the checkerboard titration method to determine the fractional inhibitory concentration (FIC) index. RESULTS: The MIC results showed that traditional antituberculous drugs had poor activity against M. chelonae. In the aminoglycoside group, tobramycin and amikacin had better activity than gentamicin. Among macrolides, clarithromycin was especially effective, with an MIC ranging from 0.125 to 1 microgram/ml. Among various beta-lactam antibiotics, imipenem was the only one to demonstrate good anti-mycobacterial activity. Of the quinolone group, ciprofloxacin was the most effective, with an MIC ranging from 0.5 to 16 micrograms/ml. Combination of an aminoglycoside with imipenem, ciprofloxacin or clarithromycin all showed antagonistic effect. CONCLUSIONS: The results suggested that amikacin, clarithromyicn, imipenem and ciprofloxacin had good in vitro antimicrobial activity against M. chelonae. However, no synergistic effect could be demonstrated for combinations of an aminoglycoside with other effective drugs.     

Characteristics of Staphylococcus aureus strains isolated from clinical and non-clinical human sources in Trinidad: susceptibility to bacteriophages and antimicrobial agents, and toxigenicity

The susceptibility of Staphylococcus aureus strains isolated from human clinical and non-clinical sources in Trinidad to bacteriophages and antimicrobial agents was determined. The ability of the strains to produce enterotoxins and toxic shock syndrome toxin-1 (TSST-1) was also investigated. Of the 554 strains tested, 454 (81.8%) were susceptible to international phage set (IPS) phages with strains isolated from bacteruria (57.1%) and bacteremia (53.3%) having a low sensitivity compared to isolates from aspirates (87.3%) and anterior nares (97.4%). All sources combined, strains were most susceptible to phages belonging to several groups (mixed). Overall, 419 (75.6%) strains were resistant to one or more of nine antimicrobial agents tested. Resistance to penicillin was most prevalent, with 413 (74.5%) strains found to be resistant. Prevalence of resistance to tetracycline, gentamicin, oxacillin, cefuroxime and ciprofloxacin was 5.1%, 2.0%, 0.7%, 0.4% and 0.4%, respectively. Of the 554 strains tested, 307 (55.4%) produced staphylococcal enterotoxins A (SEA), B (SEB), C (SEC) and D (SED) singly or in combination. Strains recovered from high vaginal swabs were least enterotoxigenic (40.0%) as compared to umbilical infection isolates which were most enterotoxigenic (78.9%). TSST-1 was produced by 95 (19.0%) out of 499 strains tested, with isolates from bacteruria found to be most toxigenic (33.3%). It was concluded that the S. aureus strains tested were highly susceptible to bacteriophages and antimicrobial agents (except penicillin) and that enterotoxigenic and TSST-1 producers were widespread and have an aetiologic potential.     

In vitro activity of temocillin, a new beta-lactamase-stable penicillin active against enterobacteria

The activity of temocillin was investigated in vitro against 523 clinical isolates of enterobacteria and Pseudomonas aeruginosa. The minimum inhibitory concentration of the new compound for all ampicillin-susceptible enterobacteria and for 90% of ampicillin-resistant enterobacteria was 16 micrograms/ml or less, a concentration readily achieved in plasma. P. aeruginosa strains were uniformly resistant to temocillin. All but 3 of a separate group of 48 enterobacteria exhibiting resistance to the combination of clavulanic acid and amoxicillin were found to be inhibited by 16 micrograms or less of temocillin per ml. The new compound also displayed good activity against a group of laboratory stock cultures selected on the basis of differential resistance to presently available beta-lactam agents. Two of these strains were cefotaxime resistant.     

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     

Efficient expression of pro-urokinase by human lymphoblastoid Namalwa KJM-1 cells using moloney retroviral promoter

The activity of antimicrobial agents against clinical isolates of Nocardia was studied by determination of the Minimal Inhibitory Concentrations (MICs) and Disk Diffusion Technique, according to the National Committee for the clinical Laboratory Standards (NCCLS). The object was: (a) to determine the 'in vitro' susceptibility of the strains that cause human mycetomas; (b) to determine the presence of different patterns of sensitivity among the regional strains; (c) to evaluate the Disk Diffusion Technique using disks commercially available with the antimicrobial concentrations normally used in the microbiological practice. Comparing the MIC values obtained with the values suggested by the National Committee for Clinical Laboratory Standards for Nocardia spp. (broth microdilution MIC breakpoints), we found that local strains are susceptible to amikacin, cefotaxime, ceftriaxone and TMP-SMZ; moderately susceptible to ampicillin and resistant to ciprofloxacin and erythromycin. The results obtained by both methods showed the presence of different patterns of sensitivity among the regional strains of N. brasiliensis. This showed strains sensitive and resistant to antibiotics. The Disk Diffusion Technique, even if it is not the adequate method to study the sensitivity patterns of different strains against antimicrobial agents, permits the differentiation between strains sensitive and resistant to antibiotics.     

Thyroid nodule and cancer in pregnant women]

157 bacterial isolates from cases with urinary tract infections (UTI) were studied for their susceptibility to some of the available quinolones as compared to other commonly used antimicrobial agents in UTI. Resistance to nalidixic acid was observed in 62.4% of isolates whereas for pefloxacin, norfloxacin, ciprofloxacin and lomifloxacin it was 54.7%, 52.5%, 51.5% and 50.3% respectively. Aminoglycosides and third generation cephalosporins showed resistance in fewer isolates. Gentamicin resistance was observed in 21% and corresponding figure for amikacin, cefotaxime and ceftriaxone was 7%, 8.9% and 12.1% respectively. Nitrofurantoin showed resistance in 36.3% of isolates and 48% isolates were resistant to cephalexin. The minimum inhibitory concentration (MIC) of quinolones was more than 64 mcg/ml which is > 8 times in resistant strains as compared to sensitive isolates.     

Bacterial pathogens and their antimicrobial susceptibility in Kumasi, Ghana

Between January, 1994 and June, 1996 a survey of bacterial isolates from clinical specimens and their antimicrobial susceptibility was performed at the Komfo Anokye Teaching Hospital, Microbiology Department, Kumasi, Ghana. A total of 11,380 bacterial isolates were cultured from eight different specimens. The sites of origin were wounds 32.2%, urine 28.1%, ear, nose and throat 3.6%, sputum 2.5% and aspirates 2.5%. Gram-negative bacteria accounted for 7955 (69.9%) isolates, the main species were Escherichia coli 47.1%, Pseudomonas spp. 16.8%, Proteus spp 14.6%, Klebsiella spp 10.2%, Neisseria gonorrhoeae 4.2%, Gram-positive bacteria contributed 3425 ((30.1%) of isolates, with Staphylococcus aureus 54.6% being the most predominant followed by Coagulase negative Staphylococcus 18.1%, Streptococcus pneumoniae 13.7% and Beta-haemolytic streptococci 4.1%. Escherichia coli showed 88% and 82% resistance to ampicillin and cotrimoxazole respectively with 78% being susceptible to gentamicin. Cefuroxime resistance in Gram-negative bacilli was 5%. As much as 30.6% and 21.7% of Streptococcus pneumoniae isolates were resistant to Penicillin and chloramphenicol respectively. Ten per cent of Staphylococcus aureus strains were susceptible to penicillin and 18% were resistant to flucloxacillin.     

Activity of pirlimycin against pathogens from cows with mastitis and recommendations for disk diffusion tests

Pirlimycin is an analog of clindamycin that will be recommended for therapy of bovine mastitis. It has good activity against staphylococci and streptococci, the major pathogens for bovine mastitis. Five hundred and thirty bacterial isolates recovered from cows with mastitis were studied to confirm the spectrum of activity and to develop recommendations for susceptibility testing. Pirlimycin is not active against isolates of Enterobacteriaceae, it varies in its activity against enterococci, and it is active against veterinary isolates of streptococci (MIC for 50% of strains tested, < or = 0.03 to 0.06 microgram/ml) and staphylococci (MIC for 50% of strains tested, 0.25 to 1.0 microgram/ml). On the basis of levels of drug attained in the milk with recommended dosing schedules, we chose MIC breakpoints of < or = 2 micrograms/ml for susceptibility and > or = 4 micrograms/ml for resistance. We also recommended a disk diffusion test using a disk containing 2 micrograms/ml and breakpoints of < or = 12 mm for resistance and > or = 13 mm for susceptibility.     

In vitro activity of fleroxacin against multiresistant gram-negative bacilli isolated from patients with nosocomial infections

In order to evaluate the in vitro activity of fleroxacin against nosocomial gram-negative organisms, 263 multiresistant gram-negative bacilli (203 Enterobacteriaceae and 60 non-fermenting gram-negative bacilli) were isolated from adult patients with nosocomial infections. The different patterns of resistance to eight different antimicrobial agents (ampicillin, carbenicillin, piperacillin, cephalothin, cefamandole, ceftazidime, gentamicin and amikacin) were determined by minimum inhibitory concentration (MIC), using the agar dilution method. The most prevalent multiresistant species isolated were Klebsiella pneumoniae (28.9%), Escherichia coli (24%) and Pseudomonas aeruginosa (12.2%). All these bacterial strains showed three to five resistance patterns to at least three different antibiotics. Resistance to ceftazidime was observed in at least one of the resistance patterns of isolated bacteria. The activity of fleroxacin against multiresistant enteric bacteria was excellent; these strains showed a susceptibility of 79-100%. The susceptibility of P. aeruginosa to antipseudomonal agents was low; however, the activity of fleroxacin against these strains was higher than 60% (MIC < or = 2 microg/ ml), broadly comparable with ciprofloxacin. The resistance to fluoroquinolones detected in this study was no cause for alarm (3%). Consequently, fleroxacin maintains a remarkable activity against Enterobacteriaceae and remains highly active against other gram-negative bacilli. Nevertheless, actions directed at preventing or limiting resistance will be crucial to maintain the viability of fluoroquinolones as important therapeutic agents.     

Salmonella bloodstream infections: report from the SENTRY Antimicrobial Surveillance Program (1997-2001)

Salmonella spp. are significant bloodstream pathogens and are routinely monitored for antimicrobial resistance by the SENTRY Antimicrobial Surveillance Program. Six hundred and one bloodstream infection (BSI) isolates of Salmonella spp., collected over a 5-year period (1997-2001) were tested for their susceptibility against 20 antimicrobial agents, comparing year and geographical region. Salmonella enterica serotype Typhi was the most frequently identified 'species' (43% of identified strains), although 'unspeciated' strains predominated overall (54.2%). The rank order for six selected drugs tested by their MIC(90) values and percentage susceptibility was: ceftriaxone (< or =0.25 mg/l; 99.5% susceptible)>ciprofloxacin (0.12 mg/l; 99.3%)> trimethoprim/sulphamethoxazole (< or =0.5 mg/l; 92.7%)>amoxycillin/clavulanate (16 mg/l; 89.7%)>ampicillin (>16 mg/l; 81.0%)>tetracycline (>8 mg/l; 79.4%). Most isolates remained highly susceptible to all 20 agents examined, with the exception of Salmonella Typhimurium (only 35.3% susceptible to tetracycline, 41.2% to ampicillin, and 61.8% to amoxycillin/clavulanate). DT104 resistance phenotypes were noted in 3.4 and nearly 60.0% of unspeciated Salmonella and S. Typhimurium, respectively. Unexpectedly, the highest overall susceptibility rates were recorded in Latin America. Fluoroquinolone resistance was observed and nalidixic acid screening MICs (< or =8 mg/l) predicted full susceptibility to ciprofloxacin. Five-year results from the SENTRY Program show no clear trend toward greater resistances in Salmonella spp. BSIs for the commonly used antimicrobial classes. With the exception of S. Typhimurium DT104, most Salmonella spp. remain highly susceptible to the tested antimicrobials that maybe utilized for Salmonella BSI.     

Why have group A streptococci remained susceptible to penicillin? Report on a symposium

In spite of 50 years of extensive use of penicillin, group A streptococci remain exquisitely susceptible to this antibiotic. This observation that continuing susceptibility has occurred despite the development of resistance to other antimicrobial agents prompted a day-long meeting at Rockefeller University (New York) in October 1996. Among the most likely explanations for this remarkable state of continued susceptibility to penicillin are that beta-lactamase may not be expressed or may be toxic to the organism and/or that low-affinity penicillin-binding proteins either are not expressed or render organisms nonviable. Other potential explanations are that circumstances favorable for the development of resistance have not yet occurred and/or that there are inefficient mechanisms for or barriers to genetic transfer. Recommended future actions include (1) additional laboratory investigations of gene transfer, penicillin-binding proteins, virulence factors, and homeologous recombination and mismatch repair; (2) increased surveillance for the development of penicillin resistance; (3) application of bioinformatics to analyze streptococcal genome sequences; and (4) development of vaccines and novel antimicrobial agents. Thus far the susceptibility of group A streptococci to penicillin has not been a major clinical or epidemiological problem. A similar observation, however, could have been made decades ago about Streptococcus pneumoniae. It is therefore vital for the scientific community to closely examine why penicillin has remained uniformly highly active against group A streptococci in order to maintain this desirable state.     

Increased prevalence of penicillin-resistant viridans group streptococci in Japanese children with upper respiratory infection treated by beta-lactam agents and in those with oncohematologic diseases

BACKGROUND: Viridans group streptococci, especially penicillin-resistant strains, have been emerging as pathogens of bacteremia in neutropenic patients with hematologic malignancies. OBJECTIVES: To survey the penicillin susceptibilities of viridans group streptococci in Japanese children with and without oncohematologic diseases and to evaluate the effect of the short term administration of beta-lactam agents on the antibiotic susceptibility. METHODS: We tested 113 isolates of viridans group streptococci by the microdilution method for the minimal inhibitory concentrations (MICs) to 10 antibiotics. We isolated 40 isolates from the throats of children with an upper respiratory infection (URI) before beta-lactam antibiotic treatment, 32 isolates after the treatment, 33 isolates in hospitalized children with oncohematologic diseases and 8 isolates from blood. RESULTS: Twenty-five isolates (62.5%) from the children with URI before treatment were penicillin-intermediate or -high level resistant (MIC > or = 0.25 microg/ml). The prevalence of those isolates after antibiotic treatment (87.5%) was significantly increased compared with that before treatment (P = 0.03). The prevalences of the penicillin-high level resistant isolates (MIC > or = 4 microg/ml) in the children with oncohematologic diseases (39.4%) and in the isolates from blood (62.5%) were significantly higher than that in the children with URI before treatment (12.5%) (P < 0.01). Decreased susceptibilities to other beta-lactam agents were observed in the penicillin-high level resistant strains. CONCLUSIONS: The high prevalence of penicillin-intermediate or -high level resistant viridans group streptococci in healthy Japanese children was documented. The administration of beta-lactam agents decreased the prevalence of penicillin-susceptible isolates in the children with URI. High prevalences of penicillin-high level resistant isolates were observed in the oncohematologic patients and in the isolates from blood.     

Comparative antimicrobial activity of RP 59,500 (quinupristin-dalfopristin), the first semisynthetic injectable streptgramin, against gram-positive cocci and other recent clinical pathogens

RP 59,500 (Quinupristin-Dalfopristin) is the first semisynthetic injectable streptogramin antimicrobial agent, which is a combination of quinupristin and dalfopristin in a 30:70 ratio. The components of RP 59,500 act synergically to provide bactericidal activity through action at different sites on bacterial ribosomes. In the present study, the antimicrobial activity of RP 59,500 was compared with those of four macrolides (erythromycin, clarithromycin, azithromycin, roxithromycin). Susceptibility testing was carried out by microdilution method on 303 strains of 10 species, especially antibiotic-resistant Gram-positive cocci. RP 59,500 was active against a wide range of Gram-positive cocci including methicillin-resistant Staphylococci and penicillin-resistant Streptococcus pneumoniae. The MICs90 of RP 59,500 against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis were both 0.25 microgram/ml, although those of four macrolides were higher than 32 micrograms/ml. The MICs90 of RP 59,500 against penicillin-sensitive, -intermediate and -resistant S. pneumoniae were all 0.5 microgram/ml, although those of four macrolides against penicillin-resistant S. pneumoniae were higher than 32 micrograms/ml. RP 59,500 also exhibited equivalent activities to the four macrolides against strains of Streptococcus pyogenes. Streptococcus agalactiae and Moraxella catarrhalis. RP 59,500 exhibited the highest activities against Enterococcus faecalis, Enterococcus faecium and Enterococcus avium strains which are intrinsically resistant to most antimicrobial agents. No cross-resistance was observed between RP 59,500 and the four macrolides, which will merit attention in future clinical trials of the agent. The effect of human serum on the MIC of RP 59,500 was studied with strains of S. aureus, S. epidermidis and E. faecalis. The presence of 20% (V/V) serum had little or no effect on the MIC, although 50% (V/V) serum increased MICs by 4-8 folds. Laboratory-induced resistance to RP 59,500 occurred in a stepwise fashion in broth cultures of S. aureus, S. epidermidis and E. facalis strains and the induction rate was slow and no more than four fold increases were observed. Population analysis was performed on RP 59,500 and the reference macrolides against S. aureus ATCC 25,923 strain. Although low frequencies (less than 0.01%) of resistant sub-population were detected with EM, CAM, AZM and RXM, no RP 59,500-resistant sub-population was detected in this study.     

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.     

Antimicrobial activity of ofloxacin against recent clinical isolates from otitis media and otitis externa]

In order to evaluate the annual changes of susceptibility, minimum inhibitory concentrations (MICs) of ofloxacin (OFLX) and 4 control drugs were determined against clinical isolates that were obtained from patients with otitis media and otitis externa during the periods between January and December 1993, and the periods between October 1996 and March 1997. The results are summarized as follows: 1. No annual changes were seen for MIC50 of OFLX, but MIC80 and MIC90 of that rose against methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci (CNS) and Pseudomonas aeruginosa from 1993 to 1996. It appears that resistance to OFLX is increasing among these bacteria. Detection frequency of highly resistant strains to OFLX (MIC > 100 micrograms/ml) was lower than to other control drugs. 2. No annual changes were seen of MIC50, MIC80 and MIC90 of OFLX against methicillin-susceptible S. aureus (MSSA), Streptococcus spp., Proteus spp. and Haemophilus influenzae. OFLX showed strong antimicrobial activities against these bacteria. 3. Since there was no large annual changes in the antimicrobial activity of OFLX against clinical isolates that were obtained from patients with otitis media and otitis externa, OFLX otic solution was considered as one of the clinically useful drugs even now.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1996). I. Susceptibility distribution

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 680 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during the period of June 1996 to May 1997. Of the above bacterial isolates, Gram-positive bacteria accounted for 30.4% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 69.6% and most of them were Escherichia coli. Susceptabilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) showed the highest activity against E. faecalis isolated from patients with UTIs. Its MIC90 was 1 microgram/ml. Imipenem (IPM) and vancomycin (VCM) were also active with the MIC90S of 2 micrograms/ml. The others had low activities with the MIC90S of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA Arbekacin (ABK) and VCM showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90S of them were 1 or 2 micrograms/ml. The others except minocycline (MINO) had low activities with the MIC90S of 32 micrograms/ml or above. 3. Staphylococcus epidermidis ABK and VCM showed the strongest activities against S. epidermis isolated from patients with UTIs. The MICs for all strains were equal to or lower than 2 micrograms/ml. Cefazolin (CEZ), cefotiam (CTM) and cefozopran (CZOP) were also active with the MIC90S of 4 micrograms/ml. Compared with antimicrobial activities of cephems is 1995, the MIC90S of them had changed into a better state. They ranged from 4 micrograms/ml 16 micrograms/ml in 1996. 4. Streptococcus agalactiae All drugs except MINO were active against S. agalactiae. ABPC, CZOP, IPM, and clarithromycin (CAM) showed the highest activities. The MICs for all strains were equal to or lower than 0.125 micromilligrams. Tosufloxacin (TFLX) and VCM were also active with the MIC90S of 0.5 micromilligrams. 5. Citrobacter freundii Gentamicin (GM) showed the highest activity against C. freundii isolated from patients with UTIs. Its MIC90 was 0.5 micrograms/ml. IPM and amikacin (AMK) were also active with the MIC90S of 1 microgram/ml and 2 micrograms/ml, respectively. Cefpirome (CPR) and CZOP were also active with the MIC90S of 8 micrograms/ml. The MIC90S of the others were 16 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 0.5 microgram/ml. The MIC90S of ciprofloxacin (CPFX) and TFLX were 1 microgram/ml, the MIC90 of AMK was 2 micrograms/ml, the MIC90S of CZOP, GM and ofloxacin (OFLX) were 4 micrograms/ml. The MIC50S of cephems except CEZ, cefmetazole (CMZ) and cefaclor (CCL) had changed into a better state in 1996, compared with those in 1995. 7. Escherichia coli All drugs except penicillins and MINO were active against E. coli. Particularly CPR, CZOP and IPM showed the highest activities against E. coli. The MIC90S of them were 0.125 microgram/ml or below. Among E. coli strains, those with low susceptibilities to cephems except CEZ, cefoperazone (CPZ), latamoxef (LMOX) and CCL have increased in 1996, compared with those in 1995. 8. Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except penicillins, with the MIC90S of 2 micrograms/ml or below. CPR had the strongest activity, the MICs for all strains were equal to or lower than 0.25 microgram/ml. Flomoxef (FMOX), cefixime (CFIX), CZOP and carumonam (CRMN) were also active with the MIC90S of 0.125 microgram/ml or below. 9. Pseudomonas aeruginosa All drugs except quinolones were not so active against P. aeruginosa with the MIC90S were 32 micrograms/ml or above. Quinolones were more active in 1996 than 1995. The MIC90S of them were between 4 micrograms/ml and 8 micrograms/ml, and the MIC50S of them were between 1 microgram/ml and 2 micrograms/ml. 10. Serratia marcescens GM showed the highest activity against S. marcescens. Its MIC90 was 1 micro