Antimicrobial susceptibility of bacterial pathogens associated with community-acquired respiratory tract infections in Asia: report from the Community-Acquired Respiratory Tract Infection Pathogen Surveillance (CARTIPS) study, 2009-2010

A multicentre resistance surveillance study [Community-Acquired Respiratory Tract Infection Pathogen Surveillance (CARTIPS)] investigating the susceptibilities of 2963 clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, meticillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus spp. from Asia against 12 antimicrobial agents was undertaken from 2009 to 2010. Based on the breakpoints for oral penicillin V recommended by the Clinical and Laboratory Standards Institute, the prevalence of penicillin-non-susceptible S. pneumoniae (PNSSP) ranged from 46% to 100%. Azithromycin and clarithromycin exhibited variable resistance rates of 0–88% against S. pneumoniae, 0–57% against MSSA and 0–76.5% against Streptococcus spp. isolates. The prevalence of extended-spectrum β-lactamase-producing K. pneumoniae varied from 5.1% to 58.5%. β-Lactamase production rates amongst H. influenzae isolates ranged from 15% to 46.6% and amongst M. catarrhalis isolates from 90% to 100%. Amongst M. catarrhalis isolates, macrolide resistance and cefaclor resistance rates of 5.8% and 1.2%, respectively, were found, mainly in Mainland China. Levofloxacin resistance rates of 0–3.9% with a MIC₉₀ (minimum inhibitory concentration causing inhibition of 90% of isolates) of 1–2 mg/L and moxifloxacin resistance rates of 0–1.7% with a MIC₉₀ of 0.125–0.5 mg/L were found amongst PNSSP isolates. Moxifloxacin was very active against Streptococcus spp., H. influenzae and M. catarrhalis isolates, with MIC₉₀ values of 0.125–0.25, 0.032–0.5 and 0.064–0.125 mg/L, respectively. These results from the CARTIPS study have confirmed some significant regional differences in the antimicrobial susceptibilities of S. pneumoniae, MSSA, K. pneumoniae, H. influenzae and Streptococcus spp. and emphasise the importance of antimicrobial surveillance programmes for guiding empirical therapy and for focusing interventional control of antimicrobial resistance in distinct geographic areas.     

Susceptibility of Canadian isolates of Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae to oral antimicrobial agents

We measured the susceptibility of Canadian isolates of three respiratory tract pathogens (Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae) to several currently approved antimicrobial agents by two different methods. We also measured the susceptibility of isolates to seven fluoroquinolones. Beta-lactamase was produced by 123/566 (21.7%) of H. influenzae isolates compared with 178/200 (89%) of M. catarrhalis isolates. For S. pneumoniae 83/374 (22.2%) isolates were penicillin resistant and of these 2.1% (8/374) showed high level resistance (MIC≥2 mg/l). Regardless of methodology, all fluoroquinolones were highly active against H. influenzae (MIC₉₀ ≤0.031 mg/l) and M. catarrhalis (MIC₉₀ ≤0.064 mg/l) isolates. Susceptibility of H. influenzae to cefuroxime and amoxycillin/clavulanic acid was 99–100% whereas 84–85.5% were susceptible to cefaclor and cefprozil. Azithromycin susceptibility ranged from 82.6 to 99.2% depending on the method. M. catarrhalis isolates were uniformly susceptible to all agents tested except amoxycillin. Cross-resistance in S. pneumoniae to all non-quinolone agents was concurrent with increasing penicillin resistance as shown by increasing MIC₉₀ values. For the fluoroquinolones tested, the rank order of potency based on MIC₉₀ values was as follows: gemifloxacin (0.031–0.063 mg/l), trovafloxacin (0.125 mg/l), moxifloxacin (0.125–0.25 mg/l), grepafloxacin (0.125–0.25 mg/l), gatifloxacin (0.5 mg/l), levofloxacin (1 mg/l) and ciprofloxacin (2 mg/l). Our study confirms either a high or increasing prevalence of antimicrobial resistant respiratory pathogens in Canada and also compares the new and old fluoroquinolones and their potential role as therapy for community-acquired infections. The prevalence of β-lactamase positive H. influenzae may have decreased from levels reported in previous studies.     

Surveillance of tigecycline activity tested against clinical isolates from a global (North America,Europe, Latin America and Asia-Pacific) collection (2016)

Tigecycline and comparators were tested by the reference broth microdilution method against 33 348 non-duplicate bacterial isolates collected prospectively in 2016 from medical centres in the Asia-Pacific (3443 isolates), Europe (13 530 isolates), Latin America (3327 isolates) and the USA (13 048 isolates). Among 7098 Staphylococcus aureus isolates tested, >99.9% were inhibited by ≤0.5?mg/L tigecycline (MIC_50/90, 0.06/0.12?mg/L), including >99.9% of methicillin-resistant S. aureus and 100.0% of methicillin-susceptible S. aureus. Tigecycline was slightly more active against Enterococcus faecium (MIC_50/90, 0.03/0.06?mg/L) compared with Enterococcus faecalis (MIC_50/90, 0.06/0.12?mg/L) and its activity was not adversely affected by vancomycin resistance when tested against these organisms. Tigecycline potency was comparable for Streptococcus pneumoniae (MIC_50/90, 0.03/0.06?mg/L), viridans group streptococci (MIC_50/90, 0.03/0.06?mg/L) and β-haemolytic streptococci (MIC_50/90, 0.06/0.06?mg/L) regardless of species and penicillin susceptibility. Tigecycline was active against Enterobacteriaceae (MIC_50/90, 0.25/1?mg/L; 97.8% inhibited at ≤2?mg/L) but was slightly less active against Enterobacteriaceae isolates expressing resistant phenotypes: carbapenem-resistant Enterobacteriaceae (MIC_50/90, 0.5/2?mg/L; 98.0% susceptible); multidrug-resistant (MIC_50/90, 0.5/2?mg/L; 93.1% susceptible); and extensively drug-resistant (MIC_50/90, 0.5/4?mg/L; 87.8% susceptible). Tigecycline inhibited 74.4% of 888 Acinetobacter baumannii isolates at ≤2?mg/L (MIC_50/90, 2/4?mg/L) and demonstrated good in vitro activity against Stenotrophomonas maltophilia (MIC_50/90, 1/2?mg/L; 90.6% inhibited at ≤2?mg/L) Tigecycline was active against Haemophilus influenzae (MIC_50/90, 0.12/0.25?mg/L) regardless of β-lactamase status. Tigecycline represents an important treatment option for resistant Gram-negative and Gram-positive bacterial infections.     

In vitro activity of ABT-773, telithromycin and eight other antimicrobials against erythromycin-resistant Streptococcus pneumoniae respiratory isolates of children

The activity of the ketolide ABT-773 against 180 erythromycin-resistant Streptococcus pneumoniae obtained from children was compared with telithromycin, azithromycin, clarithromyin, roxithromycin, clindamycin, penicillin, levofloxacin and gatifloxacin. Ketolide MICs were all ≤1 mg/l, with ABT-773 being the most potent of all drugs tested. MIC₉₀s for macrolides and azithromycin in mefE+ isolates were 16–32 compared with >128 mg/l for ermB+ isolates. ABT-773 and telithromycin MIC₉₀s for mefE+ isolates were 0.125 and 0.5, compared with 0.032 and 0.016 mg/l for ermB+ isolates and 0.5 and 1 mg/l, respectively, for isolates containing both genes. Clindamycin was active against mefE+ but not ermB+ isolates. 155 isolates were resistant to penicillin. All fluoroquinolone MICs were <1 mg/l. Further studies of ketolides for treatment of paediatric S. pneumoniae infections are warranted.     

In vitro activities of LB20304, a new fluoroquinolone

Thein vitro activity of LB20304 was evaluated against clinical isolates and compared with those of Q-35, ciprofloxacin, sparfloxacin, lomefloxacin and ofloxacin. LB20304 demonstrated 16- to 64-fold more potent activity than ciprofloxacin against gram-positive bacteria. LB20304 inhibited 90% of the isolates of methicillin-susceptibleStaphylococcus aureus (MSSA) at a concentration of 0.016 μg/ml (MIC₉₀). MIC₉₀ values of LB20304 against methicillin-resistantStaphylococcus aureus (MRSA), methicillin-susceptibleStaphylococcus epidermidis (MSSE), methicillin-resistantS. epidermidis (MRSE) andStreptococcus pneumoniae were 2 μg/ml, 0.016 μg/ml, 0.5 μg/ml and 0.031 μg/ml, respectively. LB20304 was also very active against gram-negative bacteria. AgainstEscherichia coli, Klebsiella pneumoniae, Serratia marcescens, Pseudomonas aeruginosa andAcinetobacter calcoaceticus, MIC₉₀S of LB20304 were 0.031 μg/ml, 0.25 μg/ml, 2 μg/ml, 8 μg/ml and 0.5 μg/ml, respectively. Its activity was comparable to that of ciprofloxacin but much better than those of Q-35, sparfloxacin, ofloxacin and lomefloxacin. LB20304 also exhibited the most potent activity among quinolones tested against laboratory standard strains, ofloxacin-resistant strains, β-lactamase-producing strains and anaerobic strains. The inhibitory effect (IC₅₀) of LB20304 on DNA gyrase fromMicrococcus luteus, determined by the supercoiling assay, was 8-fold more potent than that of ciprofloxacin. LB20304 did not induce topoisomerase-associated DNA cleavage even at a concentration of 10 mg/ml, although ciprofloxacin induced DNA cleavage at a concentration of 1 mg/ml.     

Antibiotic resistance and assessment of food-borne pathogenic bacteria in frozen foods

One hundred ninety-three frozen food samples collected in Korea various public bazaars from October 2006 to September 2007. Staphylococci were detected in 21.8% of frozen food samples. Staphylococcus aureus was isolated from 17 (8.8%) samples. Other staphylococci isolates were identified as S. warneri (7.8%), S. epidermidis (2.1%), S. xylosus (1.6%), S. eguorum (1%), and S. vitulinus (0.5%). Additionally, the antimicrobial susceptibility of 42 staphylococcal isolates to ten different antimicrobial agents was determined. The staphylococcal isolates demonstrated antimicrobial resistance to mupirocin (31%) oxacillin (14.3%), gentamicin (9.5%), teicoplanin (7.1%) and ciprofloxacin (7.1%). Most of the staphylococcal isolates showed high-level resistance to mupirocin (MIC₉₀, >128 μg/mL). Fortunately, most of the isolates were susceptible to vancomycin. The total bacteria and Escherichia coli count were tested to investigate the microbiological quality of frozen foods. From 193 frozen food samples, 43 (22.3%), 34 (17.6%) and 19 (9.8%) samples were shown to be of unacceptable quality due to total bacteria, coliform and E. coli counts, respectively.     

Microbiologic Effect of Bovine Cerebrospinal Fluid and Azithromycin Against Neisseria meningitidis,Streptococcus pneumoniae,and Haemophilus influenzae

Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of azithromycin against reference strains of Streptococcus pneumoniae ATCC 49619, Neisseria meningitidis ATCC 13090, and Haemophilus influenzae ATCC 49247 were determined by the macrodilution broth method with and without 10% bovine cerebrospinal fluid (CSF) supplementation. The MICs and MBCs were within one to two dilutions for N. meningitidis and S. pneumoniae, and no difference was observed for H. influenzae. Time-kill curves demonstrated enhanced killing by azithromycin when 10% bovine CSF was added to media for N. meningitidis. The minimum azithromycin concentration for a greater than 3 log₁₀ reduction in inoculum with bovine CSF was 0.03 μg/ml and without CSF was 0.12 μg/ml, a 3-fold difference. Killing was not significantly different for either H. influenzae nor S. pneumoniae. (Pharmacotherapy 1997;17(5);985–989)     

Surveillance study of the susceptibility of Haemophilus influenzae to various antibacterial agents in Europe and Canada

ABSTRACT

Background: Haemophilus influenzae is a major respiratory tract pathogen that is becoming increasingly resistant to β-lactam antibiotics.

Materials and methods: Using a microdilution method performed to Clinical and Laboratory Standards Institute (CLSI) guidelines, we determined the minimal inhibitory concentrations (MICs) of various antibacterial agents against 536 isolates of H.?influenzae. The isolates were obtained from patients with respiratory tract infections being treated in 18 European and two Canadian centres between 2006 and 2007.

Results: Levofloxacin, moxifloxacin, cefixime and cefpodoxime with MIC₉₀ values of ≤?0.03, ≤?0.03, 0.03 and 0.06?μg/mL, respectively, were the four most active agents tested. Overall, amoxicillin resistance was observed in 25.0% of the strains, but was generally reversed with the addition of clavulanic acid. In 73 strains (13.6%) resistance was due to β-lactamase (BL) production while the remainder (n?=?61; 11.4%) were BL-negative, amoxicillin-resistant (BLNAR) strains. Comparison of penicillin binding protein 3B sequences in BLNAR isolates revealed that only mutations at amino acids 502 (alanine [Ala]?→?threonine [Thr]/valine [Val]) and 526 (asparagine [Asn]?→?lysine [Lys]) were significantly associated with amoxicillin resistance among European H.?influenzae isolates (?p?<?0.0001 for both).

Conclusions: This surveillance study highlights an increased prevalence of amoxicillin-resistant strains of H.?influenzae compared with a previous study that we performed in 2004/2005. The third-generation cephalosporins cefixime and cefpodoxime, as well as amoxicillin plus clavulanic acid, continue to be very active against both BL-positive and BLNAR strains of H. influenzae, and thus remain useful treatment options for patients with respiratory tract infections.     

Comparative antimicrobial activity of ABT-773, a novel ketolide, tested against drug-resistant Gram-positive cocci and Haemophilus influenzae

The antimicrobial activity of ABT-773, a novel ketolide, was tested against 618 Gram-positive strains collected from various surveillance programmes between 1997 and 2000. ABT-773 has potent activity against Streptococcus pneumoniae (MIC₉₀, ≤0.03–0.12 mg/l), β-haemolytic streptococci (MIC₉₀, ≤0.03 mg/l) and viridans group streptococci (MIC₉₀, ≤0.03 mg/l), including erythromycin-resistant strains. In contrast, ABT-773 was less active against erythromycin-resistant Staphylococcus aureus (31% susceptible at ≤0.25 mg/l), coagulase-negative staphylococci (41% susceptible) and enterococci (30% susceptible). Haemophilus influenzae (MIC_90, 4 mg/l) was less inhibited by the two ketolides tested, and ABT-773 was generally two- to fourfold more potent than telithromycin. The ketolides appear to have potential clinical use against some Gram-positive species resistant to macrolides.     

Daptomycin activity tested against 164 457 bacterial isolates from hospitalised patients: Summary of 8 years of a Worldwide Surveillance Programme (2005–2012)

We report the results of 8 years (2005–2012) of the Daptomycin Surveillance Programme Worldwide. Consecutive non-duplicate bacterial isolates (prevalence design) were collected from patients with documented infections in 410 medical centres and were susceptibility tested by reference broth microdilution methods. A total of 164 457 Gram-positive isolates were evaluated, including 97 542 Staphylococcus aureus, 21 413 coagulase-negative staphylococci (CoNS), 29 619 enterococci and 15 883 β-haemolytic streptococci. The prevalence of daptomycin-non-susceptible isolates was extremely low for all species in all geographic regions. Overall, the highest occurrence of non-susceptible isolates was observed among CoNS (0.19%), followed by Enterococcus faecium (0.18%), S. aureus (0.05%), Enterococcus faecalis (0.02%) and β-haemolytic streptococci (0.00%). Moreover, no trend towards increased daptomycin resistance (non-susceptibility) was observed for any species in any geographic region during the study interval. Against S. aureus, the daptomycin MIC_50/90 was 0.25/0.5 mg/L in all geographic regions (99.95% susceptible overall). Only 53 daptomycin-non-susceptible S. aureus isolates were observed and the vast majority (49; 92.5%) had a daptomycin MIC value only 1 log₂ dilution above the published susceptible breakpoint. Daptomycin was also active against CoNS (MIC_50/90, 0.25/0.5 mg/L; 99.81% susceptible), E. faecalis (MIC_50/90, 1/2 mg/L; 99.98% susceptible), E. faecium (MIC_50/90, 2/4 mg/L; 99.82% susceptible) including vancomycin-non-susceptible isolates (4521 isolates; MIC_50/90, 2/2 mg/L; 99.76% susceptible), and β-haemolytic streptococci (MIC_50/90, ≤0.06/0.25 mg/L; 100.0% susceptible). In conclusion, daptomycin has remained very active against indicated species worldwide, and no significant year-to-year or regional variation in daptomycin activity has been detected.     

In vitro and in vivo antibacterial activities of garenoxacin against group G Streptococcus dysgalactiae subsp. equisimilis

In this study, garenoxacin showed potent in vitro activity against clinical isolates of group G Streptococcus dysgalactiae subsp. equisimilis [minimum inhibitory concentration for 90% of the organisms (MIC₉₀) = 0.125 μg/mL] and was superior to levofloxacin (MIC₉₀ = 1 μg/mL) and moxifloxacin (MIC₉₀ = 0.25 μg/mL). In experimental pneumonia caused by group G S. dysgalactiae subsp. equisimilis in mice, the effective dose for 50% survival (ED₅₀) of garenoxacin following single oral administration was 1.87 mg/kg, >10.7-fold and 4.6-fold less than the ED₅₀ values of levofloxacin (>20 mg/kg) and moxifloxacin (8.54 mg/kg), respectively. The area under the free serum concentration-time curve from 0-24 h (fAUC_0-24)/MIC ratio of garenoxacin in serum following oral administration of 20 mg/kg was 73.2, which was 8.7-11.4-fold and 1.4-fold greater than that of levofloxacin (6.44-8.46) and moxifloxacin (51.4), respectively. These results suggest that garenoxacin has potential for the treatment of infectious diseases caused by S. dysgalactiae subsp. equisimilis.     

In vitro antibacterial activity of ceftobiprole against clinical isolates from French teaching hospitals: proposition of zone diameter breakpoints

The aims of this study were to determine the in vitro activity profile of ceftobiprole, a pyrrolidinone cephalosporin, against a large number of bacterial pathogens and to propose zone diameter breakpoints for clinical categorisation according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum inhibitory concentration (MIC) breakpoints. MICs of ceftobiprole were determined by broth microdilution against 1548 clinical isolates collected in eight French hospitals. Disk diffusion testing was performed using 30 μg disks according to the method of the Comité de l’Antibiogramme de la Société Française de Microbiologie (CA-SFM). The in vitro activity of ceftobiprole, expressed by MIC_50/90 (MICs for 50% and 90% of the organisms, respectively) (mg/L), was as follows: meticillin-susceptible Staphylococcus aureus, 0.25/0.5; meticillin-resistant S. aureus (MRSA), 1/2; meticillin-susceptible coagulase-negative staphylococci (CoNS), 0.12/0.5; meticillin-resistant CoNS, 1/2; penicillin-susceptible Streptococcus pneumoniae, ≤0.008/0.03; penicillin-resistant S. pneumoniae, 0.12/0.5; viridans group streptococci, 0.03/0.12; β-haemolytic streptococci, ≤0.008/0.016; Enterococcus faecalis, 0.25/1; Enterococcus faecium, 64/128; Enterobacteriaceae, 0.06/32; Pseudomonas aeruginosa, 4/16; Acinetobacter baumannii, 0.5/64; Haemophilus influenzae, 0.03/0.12; and Moraxella catarrhalis, 0.25/0.5. According to the regression curve, zone diameter breakpoints could be 28, 26, 24 and 22 mm for MICs of 0.5, 1, 2 and 4 mg/L respectively. In conclusion, this study confirms the potent in vitro activity of ceftobiprole against many Gram-positive bacteria, including MRSA but not E. faecium, whilst maintaining a Gram-negative spectrum similar to the advanced-generation cephalosporins such as cefepime. Thus ceftobiprole appears to be well suited for the empirical treatment of a variety of healthcare-associated infections.     

In vitro activity of the siderophore monosulfactam BAL30072 against contemporary Gram-negative pathogens from New York City,including multidrug-resistant isolates

The in vitro activity of BAL30072 was assessed against clinical isolates from NYC hospitals, including isolates from a citywide surveillance study and a collection of isolates with well-characterised resistance mechanisms. BAL30072 was the most active β-lactam against Pseudomonas aeruginosa (MIC_50/90, 0.25/1 μg/mL), Acinetobacter baumannii (MIC_50/90, 4/>64 μg/mL) and KPC-possessing Klebsiella pneumoniae (MIC_50/90, 4/>64 μg/mL). Combining BAL30072 with meropenem resulted in a ≥4-fold decrease in the BAL30072 MIC₉₀ both for A. baumannii and K. pneumoniae. For isolates with a BAL30072 MIC > 4 μg/mL, addition of a sub-MIC concentration of colistin resulted in a four-fold decrease in the BAL30072 MIC in 44% of P. aeruginosa, 82% of A. baumannii and 23% of K. pneumoniae. Using sub-MIC concentrations, BAL30072 plus colistin was bactericidal against 4 of 11 isolates in time–kill studies. BAL30072 MICs were frequently lower for P. aeruginosa and K. pneumoniae when tested using Mueller–Hinton agar versus Iso-Sensitest agar or Mueller–Hinton broth. Against the well-characterised isolates, reduced susceptibility to BAL30072 correlated with mexA and mexX expression (P. aeruginosa), adeB expression (A. baumannii) and presence of SHV-type ESBLs (A. baumannii and K. pneumoniae). BAL30072 shows promising activity against contemporary Gram-negatives, including MDR P. aeruginosa, A. baumannii and K. pneumoniae. Enhanced activity was often present when BAL30072 was combined with meropenem or colistin. BAL30072 MICs were influenced by the testing method, particularly for P. aeruginosa and K. pneumoniae. Further in vivo studies are warranted to determine the potential clinical utility of BAL30072 alone and combined with other agents.     

In vitro activities of the newly synthesised ER-2 against clinical isolates of Mycobacterium tuberculosis susceptible or resistant to antituberculosis drugs

Two hundred isolates of Mycobacterium tuberculosis were evaluated for their susceptibility to a newly synthesised quinolone derivative, ER-2, compared with ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin. ER-2 and moxifloxacin showed the greatest activity [MIC for 90% of strains tested (MIC₉₀) = 0.5 μg/mL], although levofloxacin and ciprofloxacin showed good activity with an MIC₉₀ of 1 μg/mL. More importantly, ER-2 showed excellent activity against M. tuberculosis H37Rv both in the lungs and spleen of mice, indicating the potential therapeutic value of ER-2 against M. tuberculosis.     

In vitro andin vivo evaluations of LB10517, a novel parenteral broad-spectrum cephalosporin

Thein vitro activity of LB10517, a new catechol-substituted cephalosporin, was compared with those of E-1077, cefpirome and ceftazidime against 1034 clinical isolates collected in Japan. LB10517 showed a broad-spectrum antibacterial activity against a wide range of gram-positive and gram-negative bacteria including non-glucose fermenting rods,Pseudomonas aeruginosa. Against the methicillin-susceptible strains ofStaphylococcus aureus (MSSA) andStreptococcus pyogenes, the MIC₉₀ values of LB10517 which required to inhibit 90% of the strains were 3.13 μg/ml and 0.1 μ/ml, respectively. It was as active as E-1077 but more active than cefpirome and ceftazidime. Methicillin-resistant strains ofS. aureus (MRSA) andEnterococcus spp. were highly resistant to all the test compounds. LB10517 was highly active against most members of the familyEnterobacteriaceae, 90% of which were inhibited at a concentration of less than 0.78 μg/ml, except forEnterobacter cloacae (1.56 μg/ml) andSerratia marcescens (3.13 μg/ml). Its activity was comparable to those of E-1077 and cefpirome but it was greater than that of ceftazidime. AgainstPseudomonas aeruginosa, LB10517 showed the most potent antibacterial activity among the compounds tested. Ninety percent ofP. aeruginosa isolates were susceptible at the concentration of 0.39 μg/ml. Its activity was 32- to 128-fold higher than those of E-1077, cefpirome and ceftazidime. Against imipenem- or ofloxacinresistantP. aeruginosa, LB10517 with MIC₉₀s of 6.25 μg/ml and 3.13 μg/ml, respectively, showed 16-fold more potent activity than the other test compounds. LB10517 showed a relatively high plasma level and long plasma elimination half-life in rats (t_1/2(β), 52 min) and dogs (t_1/2(β), 103 min).     

Antibacterial effects of antibiotics and cell-free preparations of probiotics against Staphylococcus aureus and Staphylococcus epidermidis associated with conjunctivitis

Conjunctivitis, caused by bacterial infections, represents health concern and diagnosis of the disease is pivotal for the proper selection of the treatment. The main causes of bacterial conjunctivitis vary in different countries. The current study investigated the common bacterial causes of bacterial conjunctivitis from eye clinics' attendants and evaluated the effectiveness of different therapeutic approaches. Eye swabs from patients, diagnosed with conjunctivitis, were assessed microbiologically and the isolated bacteria were identified using the standard biochemical identification and sequencing of the 16S rRNA gene. Antibiotics' susceptibility of the conjunctivitis-associated bacterial pathogens was evaluated against nineteen broad-spectrum antibiotics. In the meanwhile, cell-free preparations from probiotic Lactobacillus and Bifidobacterium strains were used to evaluate their antagonistic activities. Findings from this study showed that out of 52 specimen, 17 eye swabs from patients with conjunctivitis were bacterial culture-positive. The identity of the bacterial species, using the biochemical identification system, was Staphylococcus aureus (4 isolates) and S. epidermidis (13 isolates). Staphylococcus spp. showed susceptibility to linezolid, vancomycin, novobiocin, and fluoroquinolones (norfloxacin, ofloxacin, ciprofloxacin and levofloxacin). However, isolates from the two Staphylococcus spp. expressed resistance to penicillin G, oxacillin, and cephalexin. As alternatives to antibiotics, the growth of Staphylococcus spp., including isolates with antibiotic resistance, was inhibited by cell-free preparations of the 4 probiotic Lactobacillus and the 2 Bifidobacterium strains. These findings provide evidence that topical antibiotics such as fluoroquinolones are still effective antimicrobial agents against staphylococci associated with conjunctivitis whereas probiotic preparations could be promising for further research to pave the way for their therapeutic applications against ophthalmic diseases.     

Activity of ceftolozane-tazobactam against Gram-negative pathogens isolated from lower respiratory tract infections in the Asia-Pacific region: SMART 2015-2016

The aim of this study was to investigate the susceptibility of respiratory Gram-negative bacteria to ceftolozane/tazobactam and other antibiotics in the Asia-Pacific region during 2015-2016. MICs were determined using the CLSI standard broth microdilution method and interpreted accordingly. Pseudomonas aeruginosa (1574 isolates), Klebsiella pneumoniae (1226), Acinetobacter baumannii (627) and Escherichia coli (476) accounted for 73.1% of 5342 Gram-negative respiratory pathogens. Susceptibility to ceftolozane/tazobactam of individual Enterobacteriaceae was >80%, except for Enterobacter cloacae (76.6%). Ceftolozane/tazobactam inhibited 81.9% of K. pneumoniae and 91.9% of E. coli, with respective MIC₅₀/MIC₉₀ values of 0.5/>32 and 0.25/2 mg/L. For carbapenem-susceptible, ESBL-producing K. pneumoniae and E. coli, susceptibility was 65.5% and 93.3%, respectively, and respective MIC₅₀/MIC₉₀ values were 2/>32 and 0.5/2 mg/L. Bla_{CTX-M-1 group} was most prevalent in selected ESBL-producing K. pneumoniae (40 of 54 isolates) and E. coli (15 of 22 isolates), with ceftolozane/tazobactam susceptibility rates of 50% and 80%, respectively. Bla_SHV-ESBL was the second most prevalent, and ceftolozane/tazobactam inhibited 20% of 20 K. pneumoniae isolates with bla_SHV-ESBL. The only effective antibiotics for carbapenem-non-susceptible K. pneumoniae (111 isolates) and E. coli (24 isolates) were amikacin and colistin. Ceftolozane/tazobactam was effective against almost all tested P. aeruginosa and carbapenem-non-susceptible strains, with susceptibility of 92.3% and 72.8%, respectively; the respective MIC₅₀/MIC₉₀ values were 1/4 and 2/>32 mg/L. The high susceptibility of ceftolozane/tazobactam remained in different age groups, patient locations, recovery times and countries, except Vietnam. In conclusion, ceftolozane/tazobactam was effective against most respiratory Gram-negative pathogens in the Asia-Pacific region; however, the emergence of carbapenem resistance mandates ongoing surveillance.     

2014—2018年天津市儿童医院化脓性脑膜炎病原菌分布及耐药性分析

目的 分析2014—2018年天津市儿童医院化脓性脑膜炎病原菌的分布和耐药性,为临床合理应用抗菌药物提供依据。方法 收集2014年1月—2018年12月在天津市儿童医院住院,经脑脊液或血液培养细菌阳性的化脓性脑膜炎患儿121例,统计并分析化脓性脑膜炎病原菌的分布和耐药性。结果 化脓性脑膜炎患儿的年龄分布主要为<28 d和28 d～1岁,构成比分别为26.5%、41.3%。共分离出121株病原菌,其中革兰阳性菌85株,占70.2%,主要为肺炎链球菌、表皮葡萄球菌和无乳链球菌;革兰阴性菌36株,占29.8%,主要为大肠埃希菌、肺炎克雷伯菌和铜绿假单胞菌。不同年龄段化脓性脑膜炎患儿感染的病原菌不同。肺炎链球菌、表皮葡萄球菌和无乳链球菌均对利奈唑胺和万古霉素完全敏感。肺炎链球菌对左氧氟沙星和莫西沙星也完全敏感,对克林霉素和红霉素的耐药率均高达95.6%;表皮葡萄球菌对苄青霉素、苯唑西林和红霉素的耐药率较高;无乳链球菌对克林霉素和红霉素耐药率较高,对其他抗菌药物均完全敏感。大肠埃希菌、肺炎克雷伯菌和铜绿假单胞菌均对阿米卡星完全敏感。大肠埃希菌对呋喃妥因也完全敏感,对氨苄西林、哌拉西林的耐药率高达80%;肺炎克雷伯菌对妥布霉素和环丙沙星也完全敏感,对氨苄西林的耐药率高达80.0%;铜绿假单胞菌对头孢他啶、庆大霉素和妥布霉素也完全敏感,对氨苄西林、氨苄西林/舒巴坦、头孢唑林、头孢呋辛、头孢替坦、头孢曲松、复方新诺明和呋喃妥因的耐药率均高达100.0%,对其他抗菌药物的耐药率均为25.0%。结论 不同年龄段化脓性脑膜炎患儿感染病原菌不同,临床经验用药时应根据患儿发病年龄和耐药性情况选择不同的抗菌药物,提高治疗的针对性。     

Calculation of AQCmax: comparison of five ophthalmic fluoroquinolone solutions

ABSTRACT

Objective: Ocular tissue penetration of five different ophthalmic fluoroquinolone solutions in the rabbit eye was measured and evaluated by an index of the maximum aqueous concentration (AQCmax).

Methods: Moxifloxacin 0.5% (MFLX), levofloxacin 0.5% (LVFX), gatifloxacin 0.3% (GFLX), ofloxacin 0.3% (OFLX), or tosufloxacin tosilate 0.3% (TFLX) were instilled into the eyes of white rabbits every 15?min for a total of three doses. Aqueous humor, cornea, iris/ciliary body and vitreous body were collected 10 to 240?min after instillation and drug concentrations were measured by high-performance liquid chromatography.

Results: The concentration of MFLX was the highest in each tissue, with maximum concentrations of MFLX in the aqueous humor (10.16?±?1.59?µg/mL) at 30?min after instillation, cornea (156.07?±?95.97?µg/g) and iris/ciliary body (11.92?±?4.00?µg/g) at 10?min after instillation, and vitreous body (0.099?±?0.033?µg/mL) at 30?min after instillation. The concentration of TFLX was the lowest in each tissue, with LVFX, GFLX, and OFLX sharing the mid-ranks. AQCmax?:?MIC₉₀ ratio for S.?aureus was 150.67 for MFLX, 10.6 for LVFX, 9.69 for GFLX, 3.48 for OFLX, and could not be determined for TFLX.

Conclusion: AQCmax is a useful pharmacokinetic parameter for determining the therapeutic efficacy of an ophthalmic antibiotic, especially when combined with MIC₉₀ values for intraocular pathogens. C_max of MFLX ophthalmic solution was superior in all tissues (cornea, aqueous humor, iris/ciliary body and vitreous body) among the five ophthalmic solutions studied, exceeding the MIC₉₀ of S.?aureus in all tissues, and MIC₉₀s of S.?epidermidis, B.?cereus, and P.?acnes in aqueous humor, cornea, and iris/ciliary body. AQCmax was approximately proportional to C_max in iris/ciliary body and vitreous, and may be used in combination with MIC₉₀s as an index to predict the most appropriate dose and frequency of ophthalmic antibiotics in conjunction with other PK/PD parameters. This study may provide the groundwork for calculation of AQCmax in humans.     

2008-2016年陕西省杨凌示范区医院小儿下呼吸道感染肺炎链球菌耐药性分析

目的：分析陕西省杨凌示范区医院小儿下呼吸道感染肺炎链球菌的耐药性。方法选取2008年1月—2016年1月陕西省杨凌示范区医院下呼吸道肺炎链球菌感染患儿300例,对肺炎链球菌感染的患儿年龄分布、耐药性及多重耐药性进行回顾性分析。结果下呼吸道肺炎链球菌感染患儿的年龄集中于20 d～1岁,构成比为52.0%。肺炎链球菌对克林霉素的耐药率高达97.0%,其次为阿奇霉素（93.0%）、红霉素（91.0%）,对甲氧苄啶、四环素、奎奴普丁、头孢呋辛的耐药率均高于50.0%。肺炎链球菌对头孢曲松、阿莫西林、左氧氟沙星、莫西沙星、利奈唑胺和万古霉素的耐药率均低于5.0%。300例下呼吸道肺炎链球菌中仅有21例对上述抗菌药物均敏感,对4种及以上抗菌药物耐药的占57.0%。抗菌药物的使用原因中,预防性使用例数最少,占3.00%,针对性使用和经验性使用分别为173、118例,构成比分别为57.67%、39.33%。结论临床医生根据药敏试验结果进行抗菌药物的选择,在保证治疗效果的同时避免抗生素的过度使用。