Susceptibility of Respiratory and Urinary Pathogens to Ceftibuten and Other Comparative Drugs: Results of an Italian Multicenter Survey

Summary

A survey aimed at assessing the ability of ceftibuten, a new oral third-generation cephalosporin, to eradicate in Vitro selected bacterial pathogens was conducted in 1991 in 17 microbiology laboratories evenly distributed in Italy. Over 8700 organisms collected from in- and outpatients affected mainly by respiratory and urinary tract infections were analyzed. This collection of bacteria did not include staphylococci, enterococci, Pseudomonta and other oxidative species naturally refractory to the action of most antibiotics employed.

Susceptibility to ceftibuten, cefaclor, cefuroxime, amoxicillin, amoxicillin-clavulanate, cotrimoxazole and erythromycin was assessed using a standardized agar-diffusion method. Production of β-lactamases was confirmed by the nitrocefin test. Among the microorganisms studied E. coli (32.1%) prevailed, followed by P. mirabilis (17.1%), K. pneumoniae (10.9%), 5. pyogenes (6.6%), E. cloacae (5.1%), Serratia spp. (4.5%), Enterobacter spp. (4.2%), H. influenzae (3.6%), S. pneumoniae (2.2%) and Af. catarrhalis (2%). Within this group of pathogens amoxicillin resistance, often mediated by synthesis of P-lactamases, was widely diffused (46.2%). The overall inhibitory activity of the drugs tested decreased as follows: ceftibuten (90.4%), cefuroxime (80.4%), amoxicillin-clavulanate (77.4%), cotrimoxazole (75.3%), cefaclor (72.6%), amoxicillin (53.8%) and erythromycin (32.8%). When the efficacy of the antibiotics was assessed against the collection of respiratory isolates producing β-lactamases only ceftibuten maintained the same overall potency manifested against the general population while the comparative agents were far less effective. The results of this national survey indicate that, given the low incidence of resistance among the most prevalent causative agents of respiratory and urinary tract infections, ceftibuten can be safely used at present in the empiric therapy of these conditions especially when they occur in community settings.     

Susceptibility of Eikenella corrodens to Antimicrobial Agents

Summary

Twelve Eikenella corrodens strains were isolated from dental infections and tested for their susceptibility to antimicrobial agents by an agar dilution method. All strains were susceptible to penicillin, ampicillin and tetracycline, and resistant to cephalexin and metronidazole and moderately resistant to erythromycin, gentamicin and cefaclor.     

In- Vitro Susceptibility of Borrelia burgdorferi and Borrelia hermsii to Ten Antimicrobial Agents

Summary

The in-vitro activity of ten antimicrobial agents against four strains of Borrelia burgdorferi originating both in the United States and Europe and against one isolate of B. hermsii was investigated. Ceftriaxone, erythromycin and roxithromycin were the most active drugs against both Borrelia species studied, with minimum bactericidal concentrations ranging from 0.015 μg/ml to 0.125 μ/ml.     

Susceptibility of Trichophyton rubrum to griseofulvin

Two hundred and seventy isolates of Trichophyton rubrum from 182 patients were subjected to susceptibility testing with griseofulvin according to Granade & Artis. A slight modification of the method concerning homogenization procedures gave better growth of controls in our investigation. In 245 cases an MIC could be determined. Among these isolates, seven strains from six patients presented MICs between 2 and 3 micrograms griseofulvin per ml, a value which, according to Artis et al., is to be considered as relatively resistant. The other isolates proved to be more susceptible to griseofulvin. Three of the patients showed no indication of therapeutic failure of griseofulvin treatment. The other three patients had onychomycoses of long standing and had been treated with griseofulvin previously with little or limited success. It is our conclusion that griseofulvin susceptibility testing is not a reliable instrument in explaining failure of griseofulvin therapy in Trichophyton rubrum mycoses.     

In Vitro Activity of Clarithromycin Alone or in Combination with Other Antimicrobial Agents against Mycobacterium avium-intracellulare. Complex Strains Isolated from AIDS Patients

Summary

The activity of clarithromycin and five other antimicrobial agents, namely amikacin, rifampicin, rifabutin, clofazimine and ciprofloxacin, was assessed both by an agar dilution and a radiometric method in broth on 11 Mycobacterium avium-intracellulare complex (MAC) strains, recently isolated from AIDS patients. Minimum inhibitory concentrations (MICs) radiometrically determined were, in general, several times lower than MICs assessed in agar, probably because of a partial degradation of antimicrobials during the long incubation period needed for tests in solid medium. When tested in broth, rifabutin and clofazimine showed very low MICs90 (0.24 and 0.78 μg/ml, respectively). Ciprofloxacin and clarithromycin also had MICs90 in the range of peak serum levels (1.93 and 3.76 μg/ml, respectively). Moreover, all these antimicrobials are known to concentrate several times in macrophages. MICs90 were higher for amikacin (11 μg/ml) and for rifampicin (8 μg/ml). When clarithromycin was tested against three MAC strains in combination with another drug, it showed a synergistic effect only when combined with rifampicin. Some synergistic effect was observed also when combining clarithromycin with rifampicin and amikacin, whereas in combination with rifabutin and clofazimine there was only an additive effect.     

In Vitro Susceptibility of Nondermatophyte Molds Isolated from Onycomycosis to Antifungal Drugs

Abstract

Despite many advances in antifungal drug development and therapy, onychomycosis due to nondermatophyte molds (NDM) remains difficult to treat. Using a reference microdilution method (CLSI M38-A), the antifungal susceptibility to bifonazole, ciclopiroxolamine, fenticonazole, itraconazole, ketoconazole, miconazole, terbinafine and tioconazole of 64 molds isolated from toenail onychomycosis was studied. All the strains showed good susceptibility to ciclopiroxolamine. Aspergillus had excellent susceptibility to itraconazole followed by miconazole, ketoconazole, tioconazole, fenticonazole and terbinafine. The isolated species had variable susceptibility to bifonazole. Scopulariopsis had wide MIC ranges for all antifungal drugs tested except ciclopiroxolamine. Fusarium and Acremonium had reduced susceptibility to antifungal drugs tested. Nevertheless, some strains show low MICs for ketoconazole, miconazole and tioconazole.

Studies to evaluate In Vitro susceptibility testing using CLSI methods for NDM onychomycosis should be undertaken.     

Susceptibility of clinical isolates of Fusarium to antifungal drugs

Summary. The inhibitory activities of amphotericin B, fluconazole, itraconazole, miconazole, ketoconazole and terbinafine against nine isolates from clinically apparent infections of Fusarium solani , four isolates of Fusarium moniliforme and 10 isolates of Fusarium oxysporum were determined with an agar diffusion method (Neo-sensitabs) and an agar dilution method. The inhibition zones obtained with antifungal Neo-sensitabs need very careful interpretation. We did not find a good correlation between the agar diffusion method using Neo-sensitabs preloaded with azoles and amphotericin B and the agar dilution method. Amphotericin B (12/23) and terbinafine (18/23) showed good activity. Miconazole (7/23) and ketoconazole (3/23) had poor inhibitory activity. Fluconazole and itraconazole (0/23) had no in vitro activity against any of the isolates tested.
Zusammenfassung. Die inhibitorische Aktivität von Amphotericin B, Fluconazol, Itraconazol, Miconazol, Ketoconazol und Terbinafin gegen 9 klinische Isolate von Fusarium solani , 4 von Fusarium moniliforme und 10 von Fusarium oxysporum wurde mit einer Agar-Diffusionstechnik (Neo-sensitabs) und einer Agar-Dilutionsmethode untersucht. Die Hemmhöfe mit Neo-sensitabs müssen mit Vorsicht interpretiert werden. Es wurde keine gute Korrelation zwischen der Agar-Diffusionstechnik mit Neo-sensitabs, beladen mit Azolen und Amphotericin B, und der Agar-Dilutionstechnik gefunden. Amphotericin B (12/23) und Terbinafin (18/23) zeigen eine gute Aktivität. Miconazol (7/23) und Ketoconazol (3/23) haben nur schwache inhibitorische Aktivität. Fluconazol und Itraconazol (0/23) zeigen in vitro keine Aktivität gegen die untersuchten Fusarium -Stämme.     

The Charta of Milan: Basic Criteria for the Appropriate and Accurate Use of Antibiotics: Recommendations of the Italian Society of Chemotherapy

Abstract

This article summarizes the recommendations drawn up by the Italian Society of Chemotherapy regarding the proper use of antimicrobial agents for infectious diseases.     

Zur Korrelation von Biotyp und Antimykotika-sensibilität bei Candida albicans. On the Correlation of Biotype and Antimicrobial Susceptibility in Candida albicans

Zusammenfassung: 54 rezente Candida albicans-isolate von Haut und angrenzenden Schleimhäuten wurden zunächst auf Grand der von Odds und Abbott 1983 (23) angegebenen Eigenschaften biotypisiert. Anschließend wurde ihre Antimykotikaempfindlichkeit nüt Hilfe von Agardilutions- und Mikrodilutionstest untersucht. Insgesamt fanden sich 42 verschiedene Biotypen, die im häufigsten Falle viermal vertreten waren. Die minimalen Hemmkonzentrationen (MHK) von 5-Fluorcytosin (5FC) schwankten zwischen 0,016 und mehr als 128 mg/l. Die IC₃₀-Werte nach Johnson et al. 1984 (17) reichten von 0,25 bis mehr als 64 mg/l. Bei Ketoconazol lagen die MHK-Werte zwischen 32 und 128 mg/l. Wie angesichts dieser geringen Bandbreite nicht anders zu erwarten, fand sich bei diesem Antimykotikum keine klare Korrelation zwischen Biotyp und minimalen Hemmkonzentrationen. Bei 5FC ließ sich demgegenüber eine derartige Korrelation innerhalb der Biotypengruppen 1 und 3 nachweisen: Innerhalb der Gruppe 1 erwiesen sich die mit den Kodenummern 4 und 5 als besonders resistent. Innerhalb der Gruppe 3 bestand ein entsprechender Zusammenhang mit der Kodenummer 7. Summary: 54 recent clinical mucocutaneous isolates of Candida albicans were differentiated using several different characteristics as described 1983 by Odds and Abbott (23). In addition antimicrobial susceptibility testing was performed using both the agardilution and microdilution method. 42 different biotypes were found, the most frequent one turning up four times. The minimum inhibitory concentrations (MIC) of 5-fluorocytosine (5FC) ranged from 0.016 to more than 128 mg/l. The IC₃₀ values according to Johnson et al. 1984 (17) lay between 0.25 and more than 64 mg/l. With ketoconazole the MICs ranged from 32 to 128 mg/l. As could be exspected from this small range no clear correlation could be demonstrated between biotype and MIC with this antimycotic. With 5FC, however, there was a correlation within the biotype groups 1 and 3: within group 1 the strains carrying the code numbers 4 and 5 were especially resistent to 5FC. Within group 3 this especially was the case with code number 7.     

Susceptibility of Stenotrophomonas maltophilia clinical strains in China to antimicrobial combinations

Abstract

We aimed to investigate the activity levels of several combinations of antimicrobials against Stenotrophomonas maltophilia. In this study, the antimicrobial susceptibility of S. maltophilia clinical isolates was determined, and the synergistic activity of three pairs of antimicrobial combinations was evaluated by the fractional inhibitory concentration index (FICI). The antimicrobial susceptibility in vitro against 83 S. maltophilia strains was greater for minocycline (80·7%) than for trimethoprim–sulfamethoxazole (51·8%), and levofloxacin (50·6%). The rate of resistance was highest for ticarcillin–clavulanate and ceftazidime (63·8%) and resistance to trimethoprim–sulfamethoxazole (TMP–SMX) was 48·2%. All three combinations were tested against susceptible isolates. Two of the combinations, TMP–SMX+ceftazidime and levofloxacin+ceftazidime were more effective than the combination of TMP–SMX+levofloxacin. We recommend acquiring more clinical data in order to explore combination therapy, which is a promising treatment of S. maltophilia infections.     

Comparative In Vitro Activity of Tigecycline Against Aerobic and Facultative Isolates Recovered from Hospitalized Patients: An Argentinean Multicenter Study

Abstract

Tigecycline, the 9-t-butylglycylamino derivative of minocycline is the first commercially available glycylcycline exhibiting an extended spectrum of antibacterial activity due to its capacity to evade the tetracycline ribosomal and efflux resistance mechanisms. We conducted a collaborative In Vitro study determining the activity of tigecycline compared to 14 antimicrobials against clinically relevant isolates obtained from adult patients hospitalized in 9 Argentinean institutions. Minimum inhibitory concentrations (MICs) were determined by the reference broth microdilution method. The number of isolates and MICs 50/90 (mg/L) for tigecycline were the following: Acinetobacter spp. 132 (0.5/1); Escherichia coli 220 (0.12/0.25); Klebsiella spp. 220 (0.5/1), Enterobacter spp. 205 (0.5/1); Serratia spp. 84 (0.5/2); Haemophilus influenzae 96 (0.25/0.5); Staphylococcus aureus 223 (0.12/0.25); Streptococcus pneumoniae 98 (≤0.25/1); S. agalactiae 51 (0.5/0.5); Enterococcus spp. 104 (0.06/0.12); Pseudomonas aeruginosa 169 (8/16). We conclude that tigecycline is a promising drug for the treatment of infections in hospitalized patients in Argentina.     

Susceptibility of Ureaplasma urealyticum to Tetracycline,Doxycycline, Erythromycin,Roxithromycin, Clarithromycin,Azithromycin, Levofloxacin and Moxifloxacin

Abstract

The in vitro activity of tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin was tested against 63 clinical isolates of Ureaplasma urealyticum. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined by the broth microdilution method in A7 medium. The miC50 and miC90 of the tested agents after 24 h of incubation were as follows: Tetracycline, 0.5 and 2.0 μg/ml; doxycycline, 0.125 and 0.25 μg/ml; erythromycin, 2.0 and 8.0 μg/ml; roxithromycin, 2.0 and 4.0 μg/ml; clarithromycin, 0.25 and 1.0 μg/ml; azithromycin, 2.0 and 4.0 μg/ml; levofloxacin, 1.0 and 2.0 μg/ml; and moxifloxacin, 0.5 and 0.5 μg/ml, respectively. The MIC values after 24 h and 48 h incubation differed by no more than one dilution for all the agents with the exception of doxycycline (two dilution difference for MIC₉₀). Overall, moxifloxacin was the most active agent in vitro against U. Urealyticum, with the narrowest difference between MIC and MBC values, followed closely by levofloxacin. Clarithromycin was the most active macrolide.     

Susceptibility of Candida Species to Cilofungin (LY-121019)

The antifungal activity of a new semi-synthetic lipopeptide named cilofungin (LY-121019) was studied in vitro on 102 strains of Candida and Torulopsis glabrata. A standardized protocol for susceptibility testing by means of a microtiter Sabouraud broth dilution was used. The minimal inhibitory concentrations of cilofungin for C. albicans (N = 50) ranged from 0.039 to 5.0 micrograms/ml with a geometric mean of 0.47 micrograms/ml. The same results were obtained with C. tropicalis but one strain showed higher resistance (40 micrograms/ml) suggesting an Eagle effect. The MIC for T. glabrata ranged from 5.0-40.0 micrograms/ml. C. parapsilosis and C. krusei were less susceptible (5.0-40.0 micrograms/ml). These results indicate that cilofungin exhibits a potent inhibitory action on C. albicans and C. tropicalis. This effect was lower against the other species of Candida and T. glabrata studied.     

Susceptibility of Yeast-Like Fungi to a New Antifungal Agent, LY 121019

Summary:  LY 121019, a new antifungal antibiotic agent, was tested for activity against 200 clinical isolates of Candida and other yeast-like fungi. LY 121019 had its greatest inhibitory effect on C. albicans , and C. tropicalis. C. glabrata and most other Candida species were not as sensitive. Cryptococcus and other yeast-like fungi, with the exception of a few strains, were not susceptible to LY 121019.
Zusammenfassung:  LY 121019, ein neues Antimyzetikum, wurde auf seine Aktivität gegen 200 klinische Isolate von Candida und anderen, hefeähnlichen Pilzen untersucht. LY 121019 hat seine größte Hemmwirkung gegen C. albicans und C. tropicalis. C. glabrata und die meisten anderen Candida -Arten waren nicht so empfindlich. Cryptococcus und andere, hefeähnliche Pilze waren, mit Ausnahme weniger Stämme, nicht für LY 121019 empfindlich.     

Augmentation of the Susceptibility of Human Leukemia to Lymphokine-Activated Killer (LAK) Cells by Exposure of the Leukemic Target Cells to Cytotoxic Drugs in Vitro and in Vivo

Experimental studies have shown that interleukin-2-induced lymphokine-activated killer (LAK) cells are able to lyse fresh noncultured leukemia cells and that human leukemia cells have a distinct susceptibility to LAK-cell-mediated cytolysis. Cytolysis is considerably lower with fresh noncultured leukemia cells than with the leukemia cell lines K562 and Daudi. For therapeutic considerations it would be desirable to achieve as much cytolysis as possible. The current study revealed that incubating leukemia cells with cytotoxic drugs in vitro significantly augments their susceptibility to the lytic effect of LAK cells and, more importantly that exposing leukemia cells to anticancer agents in vivo during induction chemotherapy also increases their sensitivity to LAK-cell-mediated cytolysis. These results support a possible benefit from combining chemotherapy with immunotherapeutic approaches in leukemia treatment.     

Prevalence of Type III Secretion Protein Exoenzymes and Antimicrobial Susceptibility Patterns from Bloodstream Isolates of Patients with Pseudomonas aeruginosa Bacteremia

Abstract

The purpose of this study was to determine the prevalence of two type III secretion effector proteins, exoU and exoS from bloodstream isolates of hospitalized patients with Pseudomonas aeruginosa (PSA) bacteremia, to characterize antimicrobial susceptibility patterns, and to compare mortality rates.

PSA bloodstream isolates and antibiotic susceptibility profiles were collected from a university-affiliated hospital. exoS and exoU genes were detected by polymerase chain reaction. Hospital mortality was assessed by medical chart review.

119 of 122 (97.5%) PSA bloodstream isolates contained either the exoS or exoU genes. exoS was the most prevalent (n=86; 70.5%) followed by exoU (n=31; 25.4%), both genes (n=2; 1.6%) or neither gene (n=3; 2.5%). Isolates containing the exoU gene were significantly more likely to be resistant to cefepime, ceftazidime, piperacillintazobactam, carbapenems, fluoroquinolones, and gentamicin (p<0.05 for all). Mortality was high in patients with PSA bacteremia and did not differ among patients infected with the exoS isolates (n=37; 43%) or exoU isolates (n=11; 35%).

One of two type III secretion effector proteins were almost universally present in PSA bloodstream isolates. Isolates containing the exoU gene were more likely to be resistant to multiple antibiotics.     

脑胶质瘤细胞系对细小病毒MVM和H1易感性的研究

[目的]测定人胶质瘤细胞系A172,U87MG,U138,U373,和鼠胶质瘤细胞系GL261与MT539对细小病毒MVM和H1的易感性,并观察野生型病毒在肿瘤细胞内部繁殖情况.[方法]体外培养肿瘤细胞,分别用不同剂量的MVM和H1病毒感染GL261,MT539和A172,U87MG,U138,U373细胞1h,继续培养5d,每天进行活细胞计数.空斑形成试验测定感染病毒(MOI=0.1)5d后细胞内部及细胞培养上清中的病毒总量.[结果]与未感染细胞(对照)比较,U138,U373,GL261细胞在MOI 2和5的病毒剂量感染后活细胞数目明显减少,U87细胞数基本维持不变,A172和MT539细胞数轻微增加.MOI=0.1的病毒剂量对细胞的作用与对照没有差异.空斑形成试验结果表明U373和GL261在MOI=0.1的病毒感染5d后细胞内和培养上清中总病毒量略高于初始病毒量,其它细胞的总病毒量均低于初始病毒量.[结论]不同胶质瘤对细小病毒的易感性不同,U138,U373,GL261细胞对细小病毒H1或MVM易感,U87细胞次之,A172和MT539细胞不敏感.U373和GL261细胞有弱的产生子病毒的能力.     

Comparative Study of the In Vitro Antibacterial Activity of Ciprofloxacin and Thirteen other Antimicrobial Drugs with Respect to Recently Isolated Pathogens

Summary

The in vitro antibacterial activity of ciprofloxacin and 13 other antimicrobial drugs was evaluated with respect to 569 pathogens, mainly isolated from urine. Ciprofloxacin was found active in 96.1% of all of the Gram-positive and Gram-negative strains tested, amikacin in 90.6%, ceftazidime in 89.8%, ceftriaxone in 85.3%, piperacillin in 82.7%, tobramycin in 82.6%, gentamicin in 81.5%, aztreonam in 78.3%, nitrofurantoin in 72.6%, cotrimoxazole in 71.6%, cinoxacin in 71.0%, pipemidic acid in 70.6%, nalidixic acid in 66.7%, ampicillin in 50.1%. Ciprofloxacin was found to be the most active of the drugs studied against the bacterial strains which cause urinary, respiratory and other infections.     

Susceptibility to antifungal agents of Candida species isolated from paediatric and adult patients with haematological diseases

Summary The susceptibility to six antifungals: amphotericin B (AMF), 5-fluorocytosine (5-F), miconazole (MIK), ketoconazole (KET), fluconazole (FLU) and itraconazole (ITR) was tested among 206 Candida spp. isolated from paediatric and adult patients with haematological malignancies. To determinate the susceptibility the commercial microdilution method Fungitest (Bio-Rad, France) was used. The strains were classified as susceptible, intermediate susceptible, or resistant on the base of the growth in following breakpoint concentrations of particular drugs: 2 and 8 microg ml(-1) for AMF, 2 and 32 microg ml(-1) for 5-F, 0.5 and 8 microg ml(-1) for MIK, 0.5 and 4 microg ml(-1) for KET and ITR, and 8 and 64 microg ml(-1) for FLU. The highest activity to overall species showed AMF (only one resistant strain) and 5-F (85% susceptible strains). Most of C. albicans isolates were susceptible to tested azoles. The percentages of C. albicans resistant to FLU, ITR, KET and MIK were 4, 11, 8, and 0.8%, respectively. The less susceptible to azoles were C. glabrata and C. krusei (14% and 44% isolates resistant to FLU). A non-albicans Candida isolated from adult patients receiving KET prophylaxis was more frequently resistant to FLU than isolates from patients without previous exposure to azoles (P < 0.05). We did not observe differences in the susceptibility of Candida strains isolated from children compared with those from adults.