In vitro and in vivo activities of ticarcillin-loaded nanoliposomes with different surface charges against Pseudomonas aeruginosa (ATCC 29248)

Background

Pseudomonas aeruginosa exhibits multiple antibiotic resistance mechanisms. Different studies have shown that entrapment of antibiotics into liposomes could increase their anti-Pseudomonas activity. The objectives of this study were to prepare ticarcillin loaded-nanoliposomes with variable surface charges and evaluate their in vitro and in vivo efficacies against Pseudomonas aeruginosa (ATCC 29248).

Methods

Ticarcillin-loaded nanoliposomes with positive, negative and neutral surface charges were prepared by extrusion method. Ticarcillin encapsulation efficacies for different formulations were measured by HPLC method. Minimum inhibitory concentration (MIC) of ticarcillin nanoliposomal forms against strain ATCC 29248 were determined by broth dilution method. The killing rate of Pseudomonas aeruginosa was exposed to various concentrations of ticarcillin in free and nanoliposomal forms were analyzed. Ultimately, in vivo therapeutic efficacy of nanoliposomes in burned mice skin infected with strain ATCC 29248 was investigated.

Results

The encapsulation efficacies for ticarcillin-loaded cationic nanoliposomes were significantly higher (76% ± 0.17) than those of neutral (55% ± 0.14) and anionic (43% ± 0.14) nanoliposomes. The MIC of free, cationic, neutral and anionic nanoliposomal forms of ticarcillin against ATCC 29248 were to 24, 3, 6 and 48 mg/L, respectively. The killing rates of ticarcillin-loaded cationic nanoliposomes were higher than those of free and other drug formulations. Treatment by ticarcillin-loaded nanoliposomes with positive, neutral and negative surface charges resulted in almost 100, 60 and 20% survival rates, respectively.

Conclusion

Our data suggested that cationic ticarcillin-loaded nanoliposomes because of high effectiveness would be a good choice to treatment of Pseudomonas aeruginosa infections.     

Evaluation of Galleria mellonella larvae for measuring the efficacy and pharmacokinetics of antibiotic therapies against Pseudomonas aeruginosa infection

The aim of this study was to determine whether Galleria mellonella larvae can be used (i) as an in vivo infection model for Pseudomonas aeruginosa and (ii) for evaluating the pharmacokinetics and efficacy of antipseudomonal antibiotics. Two strains of P. aeruginosa were employed, NCTC 10662 (antibiotic-susceptible) and NCTC 13437 (multidrug-resistant). Larvae were infected with increasing doses of either P. aeruginosa strain to investigate the effect of inoculum size on survival. Subsequently, infected larvae were treated with a range of antibiotics to examine whether these agents were effective against P. aeruginosa infection in vivo and whether the efficacy of these drugs matched the known susceptibilities of each bacterial strain. Larval burden of P. aeruginosa was also determined after infection and treatment with cefotaxime. Pharmacokinetic properties of the antibiotics tested were measured using a well diffusion assay to determine the concentration of antibiotics in larval haemolymph over time. Galleria mellonella larvae were sensitive to P. aeruginosa infection, and increasing inoculum doses of live cells resulted in greater larval mortality. Heat-killed bacteria had no detrimental effect on survival. Antibiotic efficacy against P. aeruginosa-infected G. mellonella correlated with the measured in vitro sensitivities of the two strains tested. The therapeutic benefit arising from administration of cefotaxime correlated with a reduced burden of bacteria present in the haemolymph. There was a clear correlation between measured antibiotic pharmacokinetics and the therapeutic effect. This study strongly supports future application of the G. mellonella infection model to initial studies of novel antipseudomonal treatments.     

Ability of Chitosan Gels to Disrupt Bacterial Biofilms and Their Applications in the Treatment of Bacterial Vaginosis

Recurrence of bacterial vaginosis is attributed to the inability of various formulations to disrupt bacterial biofilms. A negatively charged polysaccharide matrix coats the bacterial communities in the biofilm and restricts the penetration of antibiotics. Therefore, bacteria in the deeper segments of the biofilm persist and perpetuate the infection. In this study, we have tested the efficacy of two bioadhesive polymers, cationic chitosan and anionic polycarbophil, to disrupt Pseudomonas aeruginosa biofilms grown in the Center for Disease Control bioreactor as well as on the 96-well plates. The biofilms were treated with various concentrations of polycarbophil and chitosan at pH 4 or 6. Biofilm integrity following various treatments was evaluated by crystal violet stain and laser confocal microscopy employing Syto9 (live-cell stain) and propidium iodide (dead-cell stain). These studies demonstrated that chitosan gel disrupts the P. aeruginosa biofilm more effectively than does polycarbophil; and this effect is independent of the pH and charge densities on either polymers. © 2013 U.S. Government. 102:2096–2101, 2013     

Nanophyto-gel against multi-drug resistant Pseudomonas aeruginosa burn wound infection

Burn wound is usually associated by antibiotic-resistant Pseudomonas aeruginosa infection that worsens and complicates its management. An effective approach is to use natural antibiotics such as cinnamon oil as a powerful alternative. This study aims to investigate topical nanostructured lipid carrier (NLC) gel loaded cinnamon oil for Pseudomonas aeruginosa wound infection. A 2⁴ full factorial design was performed to optimize the formulation with particle size 108.48 ± 6.35 nm, zeta potential −37.36 ± 4.01 mV, and EE% 95.39 ± 0.82%. FTIR analysis revealed no excipient interaction. Poloxamer 407 in a concentration 20% w/w NLC gel was prepared for topical application. Drug release exhibited an initial burst release in the first five hours, followed by a slow, sustained release of up to five days. NLC-cinnamon gel has a significant ability to control the drug release with the lowest minimum inhibitory concentration again P. aeruginosa compared to other formulations (p < .05). In vivo study also showed NLC-cinnamon gel effectively healed the infected burned wound after a six-day treatment course with better antibacterial efficacy in burned animal models. Histological examination ensured the tolerability of NLC-cinnamon gel. The results suggest that nanoparticle-based cinnamon oil gel is a promising natural product against antibiotic-resistant strains of P. aeruginosa in wound infection.     

Co-Delivery of Ciprofloxacin and Colistin in Liposomal Formulations with Enhanced <Emphasis Type="BoldItalic">In Vitro</Emphasis> Antimicrobial Activities against Multidrug Resistant <Emphasis Type="BoldItalic">Pseudomonas aeruginosa</Emphasis>

Purpose

This study aims to develop liposomal formulations containing synergistic antibiotics of colistin and ciprofloxacin for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa.

Methods

Colistin (Col) and ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate gradient. Particle size, encapsulation efficiency, in vitro drug release and in vitro antibiotic activities were evaluated.

Results

The optimized liposomal formulation has uniform sizes of approximately 100 nm, with encapsulation efficiency of 67.0% (for colistin) and 85.2% (for ciprofloxacin). Incorporation of anionic lipid (DMPG) markedly increased encapsulation efficiency of colistin (from 5.4 to 67.0%); however, the encapsulation efficiency of ciprofloxacin was independent of DMPG ratio. Incorporation of colistin significantly accelerated the release of ciprofloxacin from the DMPG anionic liposomes. In vitro release of ciprofloxacin and colistin in the bovine serum for 2 h were above 70 and 50%. The cytotoxicity study using A549 cells showed the liposomal formulation is as non-toxic as the drug solutions. Liposomal formulations of combinations had enhanced in vitro antimicrobial activities against multidrug resistant P. aeruginosa than the monotherapies.

Conclusions

Liposomal formulations of two synergistic antibiotics was promising against multidrug resistant P. aeruginosa infections.

     

Binary Medical Nanofluids by Combination of Polymeric Eudragit Nanoparticles for Vehiculization of Tobramycin and Resveratrol: Antimicrobial,Hemotoxicity and Protein Corona Studies

The development of smart nanoparticles (NPs) became a trend to enhance the delivery of drugs. In the present work, Tobramycin (TB), an aminoglycoside antibiotic that displays several undesirable side effects, has been encapsulated into cationic Eudragit®E100 (E100) NPs for the treatment of infections caused by Pseudomonas aeruginosa. Combination with neutral Eudragit®NE30D (NE30D) NPs containing resveratrol (RSV), a strong natural antioxidant, increased the antimicrobial activity of TB (75% higher than free TB). NPs were stabilized with 1.0% (w/v) poloxamer 188 (P188) or poloxamer 407 (P407) as surfactants. E100 NPs showed 83.3 ± 8.5%, and 70.1 ± 2.7 encapsulation efficiency (EE) of TB with P188 and P407 coatings, respectively. The presence of NPs was confirmed by DLS and TEM studies. TB was controlled released from NPs for 6 h. Hemotoxicity tests of NPs in the range of MIC values on human blood gave negative results. Analysis of Surface Plasmon Resonance verified that NE30D/P407/RSV does not interact with plasma proteins BSA, IgG or fibrinogen, besides E100/P188/TB interact with BSA, findings that are compatible with a negligible in vivo clearance of the nanovehicles. The obtained results show a potential binary fluid composed of two NPs to highly improve the effectiveness of conventional antibiotics.     

Caffeic Acid Phenethyl Ester Loaded Electrospun Nanofibers for Wound Dressing Application

Electrospinning is an advantageous method with a wide usage area, which enables the production of materials consisting of nano-thickness fibers. In this study, caffeic acid phenethyl ester (CAPE) molecule was loaded onto the poly(lactic-co-glycolic acid) (PLGA) nanofibers and obtained nanofibers were physicochemically and biologically investigated for the first time in the literature. The existence of CAPE molecules, loaded on PLGA membranes by dropping and spraying methods, was evaluated by a comparative investigation of Fourier-transform infrared (FTIR) spectra and X-Ray diffraction (XRD) patterns. Fiber morphology of the membranes was investigated by scanning electron microscope (SEM). CAPE release and swelling behaviors of the membranes were studied in vitro. The radical scavenging activity of CAPE-loaded wound dressing materials was determined by using an antioxidant assay. The antimicrobial properties of PLGA and CAPE-loaded PLGA membranes were evaluated against S. aureus, P. aeruginosa and C. albicans strains by the time-kill method. The biocompatibility study of the obtained CAPE-loaded fibers conducted on human fibroblast cell line and wound healing promoting effect of the fibers was investigated in vitro scratch assay.The results show that CAPE-loaded PLGA membranes are highly antimicrobial against all strains used in the experiment. Additionally, the results show that they are biocompatible and have wound healing properties on human fibroblasts.     

Release of large amounts of lipopolysaccharides from Pseudomonas aeruginosa cells reduces their susceptibility to colistin

Pseudomonas aeruginosa is an important etiological agent of opportunistic infections. Injectable colistin is available as a last-line treatment option for multidrug-resistant P. aeruginosa infections. When cells were inoculated at a high number, colistin-susceptible P. aeruginosa grew on agar medium containing colistin at a concentration 10-fold higher than the minimum inhibitory concentration without acquiring colistin resistance. This study examined the responsible mechanism for growth in the presence of a high concentration of colistin. Cell wash fluid derived from P. aeruginosa efficiently reduced colistin antimicrobial activity. This reduction was mediated by lipopolysaccharide (LPS) in the wash fluid. Extracellular LPS inhibited colistin activity more effectively than cell-bound LPS in fixed cells. Cell wash fluids from Escherichia coli and Acinetobacter baumannii also reduced colistin activity; however, they were less potent than those from P. aeruginosa. The amount of LPS in cell wash fluid from P. aeruginosa was approximately 10-fold higher than that in fluid from E. coli or A. baumannii. In conclusion, cell-free LPS derived from bacterial cells inhibited the antimicrobial activity of colistin, and this effect was greatest for P. aeruginosa. Thus, large amounts of broken and dead cells of P. aeruginosa at infection foci will reduce the effectiveness of colistin, even against cells that have not yet acquired resistance.     

Biofilm formation and serum susceptibility in Pseudomonas aeruginosa

Pseudomonas aeruginosa (P. aeruginosa) is one of the most important opportunistic pathogens. The pathogenicity of P. aeruginosa has been associated with multiple bacterial virulence factors. The aim of this study was to evaluate the association between P. aeruginosa strains obtained from various clinical samples and resistance to antibiotics and pathogenicity factors, such as resistance to serum bactericidal activity and biofilm formation. This study included 121 P. aeruginosa strains isolated from clinical samples; 65 of the isolated P. aeruginosa strains were carbapenem-resistant, and 56 were carbapenem-sensitive. Carbapenem-resistant P. aeruginosa strains were more often resistant to the majority of tested antibiotics, compared to carbapenem-sensitive strains. We did not find any statistically significant difference between resistance to carbapenems and serum resistance and ability of tested P. aeruginosa strains to produce biofilms. Carbapenem-resistant P. aeruginosa strains were recovered from the urinary tract significantly more often (75.0%) than carbapenem-sensitive P. aeruginosa strains (25.0%). Carbapenem-sensitive P. aeruginosa strains were recovered significantly more often from the respiratory tract than carbapenem-resistant strains, 60.0% and 40.0%, respectively. All the P. aeruginosa strains recovered from blood were serum-resistant. P. aeruginosa strains recovered from the respiratory tract and wounds were significantly frequently serum sensitive, 95.6% and 56.6%, respectively. We did not find any differences in biofilm production among the P. aeruginosa strains recovered from different sources.     

Comparison of octenidine dihydrochloride (Octenisept®), polihexanide (Prontosan®) and povidon iodine (Betadine®) for topical antibacterial effects in Pseudomonas aeruginosa-contaminated,full-skin thickness burn wounds in rats

Pseudomonas aeruginosa is one of the most frequently isolated organisms from infected burn wounds and a significant cause of nosocomial infection and septic mortality among burn patients. In this animal study, three antiseptic agents which were Octenidine dihydrochloride (Octenisept®, Schülke &; Mayr, Norderstedt, Germany), polyhexanide (Prontosan®, B. Braun, Melsungen AG, Germany) and povidon iodine (Betadine, Purdue Pharma L.P, Stamford, USA) were compared to assess the antiseptic effect of their applications on experimental burn wounds in in rats contaiminated with P. aeruginosa. All treatment modalities were effective against P. aeruginosa because there were significant differences between treatment groups and control groups. The mean eschar concentrations were not different between polyhexanide and povidon iodine groups, but there were significant differences between the octenidine dihydrochloride group and the other treatment groups, indicating that the Octenidine dihydrochloride significantly eliminated P. aeruginosa more effectively in the tissues compared to the to other agents. All treatment modalities were sufficient to prevent the P. aeruginosa invasion into the muscle and to cause systemic infection. In conclusion, Octenidine dihydrochloride is the most effective antiseptic agent in the treatment of the P. aeruginosa-contaminated burn wounds; Octenidine dihydrochloride can be considered as a treatment choice because of its peculiar ability of limit the frequency of replacing wound dressings.     

Azithromycin potentiates avian IgY effect against Pseudomonas aeruginosa in a murine pulmonary infection model

Cystic fibrosis (CF) patients are at risk of acquiring chronic Pseudomonas aeruginosa lung infections. The biofilm mode of growth of P. aeruginosa induces tolerance to antibiotics and the host response; accordingly, treatment failure occurs. Supplemental azithromycin has proven beneficial in CF owing to potential immunomodulatory mechanisms. Clinical studies have demonstrated a reduction in exacerbations in CF patients by avian IgY anti-Pseudomonas immunotherapy. We hypothesise that azithromycin pre-treatment could potentiate the observed anti-Pseudomonas effect of IgY opsonisation in vivo. Evaluation of phagocytic cell capacity was performed using in vitro exposure of azithromycin pre-treated human polymorphonuclear neutrophils to IgY opsonised P. aeruginosa PAO3. A murine lung infection model using nasal planktonic P. aeruginosa inoculation and successive evaluation 24 h post-infection was used to determine lung bacteriology and subsequent pulmonary inflammation. Combined azithromycin treatment and IgY opsonisation significantly increased bacterial killing compared with the two single-treated groups and controls. In vivo, significantly increased bacterial pulmonary elimination was revealed by combining azithromycin and IgY. A reduction in the inflammatory markers mobiliser granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein 2 (MIP-2) and interleukin 1 beta (IL-1β) paralleled this effect. Combination of azithromycin and anti-Pseudomonas IgY potentiated the killing and pulmonary elimination of P. aeruginosa in vitro and in vivo. The augmented effect of combinatory treatment with azithromycin and IgY constitutes a potential clinical application for improving anti-Pseudomonas strategies.     

Collagen nanofiber containing silver nanoparticles for improved wound-healing applications

Electrospun nanofibers showing great promise for fabricating nanostructured materials might help to improve the quality of wound care. The present study aimed to investigate the wound-healing potential of collagen nanofiber mats containing silver nanoparticles. Silver nanoparticles (AgNPs) synthesized by the chemical reduction method were incorporated in collagen nanofibers during the electrospinning process. Characterization of electrospun nanofiber mats revealed a mean fiber diameters in the range of 300–700?nm with a sustained release of silver ions shown to follow pseudo-order kinetics. MIC of AgNPs against Staphylococcus aureus and Pseudomonas aeruginosa were evaluated using micro-dilution assay and further antimicrobial activity of fabricated nanofibers was performed. Finally, in vivo studies were performed to demonstrate the wound-healing efficacy of composite nanofibers. In vitro results confirmed the potential antimicrobial efficacy provided by AgNPs and AgNPs composite nanofibers, essential to provide an aseptic environment at the wound site. In vivo study revealed that the rate of wound healing of the composite nanofiber mats was found to be accelerated compared with plain collagen nanofibers. Histology analysis revealed an accelerated re-epithelization, collagen production, and better wound contraction with AgNPs composite collagen nanofibers.     

The use of cisplatin-loaded mucoadhesive nanofibers for local chemotherapy of cervical cancers in mice

Polymer-based local drug delivery system may be suitable for the treatment of cervix cancer. A pilot study was carried out to examine the efficacy of cisplatin-loaded poly(ethylene oxide)/polylactide composite electrospun nanofibers as a local chemotherapy system against cervical cancer in mice via vaginal implantation. The nanofibers were proven to have good mucoadhesive property by in vitro mucoadhesion test and in vivo vaginal retention evaluation. An orthotopic cervical/vaginal cancer model was established by injecting murine cervical cancer U14 cells into the vaginal submucosa nearby the cervix. By inserting the nanofibers mat into the vagina of mice, the cisplatin released from the fiber-mat showed a much more accumulation in the vagina/cervix region than in the peripheral organs such as kidneys, liver, or blood, in contrary to the case of intravenous (i.v) injection. The in vivo trials showed that a better balance between anti-tumor efficacy and systemic safety was achieved in nanofibers group than that in i.v injection group at the equal drug dose. Therefore, electrospun nanofibers present a promising approach to the local drug delivery via vagina against cervical cancer.     

Multicenter study of ceftolozane/tazobactam for treatment of Pseudomonas aeruginosa infections in critically ill patients

BackgroundThis study aimed to assess the efficacy of ceftolozane-tazobactam (C/T) for treating infections due to Pseudomonas aeruginosa (P. aeruginosa) in critically ill patients.Patients and MethodsA multicenter, retrospective and observational study was conducted in critically ill patients receiving different C/T dosages and antibiotic combinations for P. aeruginosa infections. Demographic data, localisation and severity of infection, clinical and microbiological outcome, and mortality were evaluated.ResultsNinety-five patients received C/T for P. aeruginosa serious infections. The main infections were nosocomial pneumonia (56.2%), intra-abdominal infection (10.5%), tracheobronchitis (8.4%), and urinary tract infection (6.3%). Most infections were complicated with sepsis (49.5%) or septic shock (45.3%), and bacteraemia (10.5%). Forty-six episodes were treated with high-dose C/T (3 g every 8 hours) and 38 episodes were treated with standard dosage (1.5 g every 8 hours). Almost half (44.2%) of the patients were treated with C/T monotherapy, and the remaining group received combination therapy with other antibiotics. Sixty-eight (71.6%) patients presented a favourable clinical response. Microbiological eradication was documented in 42.1% (40/95) of the episodes. The global ICU mortality was 36.5%. Univariate analysis showed that 30-day mortality was significantly associated (P < 0.05) with Charlson Index at ICU admission and the need of life-supporting therapies.ConclusionsC/T appeared to be an effective therapy for severe infections due to P. aeruginosa in critically ill patients. Mortality was mainly related to the severity of the infection. No benefit was observed with high-dose C/T or combination therapy with other antibiotics.     

Amphotericin B-Loaded Poly(lactic-co-glycolic acid) Nanofibers: An Alternative Therapy Scheme for Local Treatment of Vulvovaginal Candidiasis

Vulvovaginal candidiasis is an inflammation localized in the vulvovaginal area. It is mostly caused by Candida albicans. Its treatment is based on the systemic and local administration of antifungal drugs. However, this conventional therapy can fail owing to the resistance of the Candida species and noncompliance of patients. Amphotericin B-loaded poly(lactic-co-glycolic acid) nanofibers are single-use, antifungal, controlled drug delivery systems, and represent an alternative therapeutic scheme for the local treatment of vulvovaginal candidiasis. Nanofibers were characterized by analytical techniques and with an in vitro drug delivery study. In vitro and in vivo fungicidal activity of amphotericin B released from nanofibers was evaluated using the agar diffusion method and an experimental murine model of vulvovaginal candidiasis, respectively. Analytical techniques showed that amphotericin B was physically mixed in the polymeric nanofibers. Nanofibers controlled the delivery of therapeutic doses of amphotericin B for 8 consecutive days, providing effective in vitro antifungal activity and eliminated the in vivo vaginal fungal burden after 3 days of treatment and with only one local application. Amphotericin B-loaded poly(lactic-co-glycolic acid) nanofibers could be potentially applied as an alternative strategy for the local treatment of vulvovaginal candidiasis without inducing fungal resistance, yet ensuring patient compliance.     

2016—2018年南京市儿童医院铜绿假单胞菌的分布及耐药性分析

目的 回顾性分析2016—2018年南京市儿童医院铜绿假单胞菌的分布及其耐药特点。方法 对送检标本进行分离和培养,并对分离出的铜绿假单胞菌的分布及耐药性进行分析。结果 2016—2018年分离出铜绿假单胞菌分别为379、455和483株,检出率分别为4.17%、4.76%、5.15%,呈逐年递增。分离菌株数量最多的科室是普外科,共分离317株（24.07%）;标本来源以痰液为主,共737株（55.96%）。铜绿假单胞菌对大部分抗菌药物的耐药率较低,对环丙沙星、左氧氟沙星的耐药率仅为0.30%、0.53%;对亚胺培南、氨曲南、哌拉西林的耐药率较高,但也仅为20.88%、17.62%、11.62%,对其余抗菌药物的耐药率均小于10%。共检出158株多重耐药铜绿假单胞菌,平均检出率为12%,检出较多的科室为新生儿重症监护室。结论 铜绿假单胞菌是儿童医院感染的常见致病菌,易产生多重耐药性,了解其临床分布和耐药性变迁,以期为临床治疗提供最新的耐药性资料,以便更好地控制铜绿假单胞菌的感染。     

2013-2015年天津市人民医院病原菌的耐药性和抗菌药物用量的相关性分析

目的 分析天津市人民医院2013—2015年抗菌药物使用情况和病原菌耐药性,分析抗菌药物用量与细菌耐药性的相关性,指导临床合理用药.方法 统计天津市人民医院2013年1月—2015年12月病原菌的分布、耐药性和抗菌药物的使用情况,并采用Pearson法对病原菌的耐药性与抗菌药物用量的相关性进行分析.结果 2013—2015年分离出病原菌25134株,以革兰阴性杆菌居多,其次为革兰阳性球菌,前5位分别为大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌、鲍曼不动杆菌、凝固酶阴性葡萄球菌.金葡菌属对青霉素、红霉素耐药率偏高;粪肠球菌对绝大多数所测试抗菌药物的耐药率均显著低于屎肠球菌.鲍曼不动杆菌对大多种抗菌药物的耐药率明显上升,对碳氢霉烯的耐药率增长迅速.铜绿假单胞菌的耐药情况较好.应用抗菌药物用药频度(DDDs)排名前5位集中在头霉素、哌拉西林钠他唑巴坦、头孢菌素类,其中头霉素类药物头孢西丁、头孢米诺连续3年均居前5位.特殊级抗菌药物比阿培南、亚胺培南DDDs增长迅速.鲍曼不动杆菌对哌拉西林他唑巴坦、美罗培南的耐药率与其DDDs显著相关(P<0.05);大肠埃希菌、肺炎克雷伯菌对头孢西丁的耐药率与其DDDs显著相关(P<0.05);其余病原菌耐药率与DDDs的相关性较小,无统计学意义.结论 天津市人民医院2013—2015年住院抗菌药物监控指标均达标,部分病原菌耐药性呈持续下降趋势,但随着头霉素类和碳氢霉烯类抗菌药物的大量使用,细菌耐药形势依然严峻,需加强临床抗菌药物的使用管理和细菌耐药性监测.     

Pseudomonas aeruginosa : résistance et options thérapeutiques à l’aube du deuxième millénaire

ObjectivesTo present to the clinician an overview of the pathologies caused by P. aeruginosa (clinical manifestations, antibiotic resistance, diagnostic, present and future therapeutic options) based on an analysis of the recent literature and on the opinions of specialists.Main PointsPseudomonas aeruginosa can cause a variety of nosocomial infections and can invade almost all anatomical sites (with a preference for the respiratory tract, especially in cystic fibrosis patients). Resistance is frequent and can be native (constitutive expression of β-lactamases and/or efflux pumps; low permeability of the outer membrane), but also acquired (genes coding for antibiotic-degrading enzymes, overexpression of efflux pumps, decreased permeability of porins, target mutations). These mechanisms often confer upon the organism a multiresistance phenotype, making susceptibility testing essential. The initial empiric treatment will most often be a combined therapy, based on local epidemiology (typically a β-lactam plus an aminoglycoside or a fluoroquinolone). This treatment will need to be readjusted as soon as possible based on susceptibility determinations, optimized use of the antibiotics selected, and clinical outcome. Colistin is useful when dealing with multiresistant isolates. Therapeutic innovations remain scarce.ConclusionsInfections caused by P. aeruginosa are potentially frightening. Treatment requires a correct diagnostic and rests upon a rational selection of antibiotics, the sue for which must be optimized on pharmacodynamic basis.     

Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience

This study describes the largest clinical experience using ceftolozane/tazobactam (C/T) for different Pseudomonas aeruginosa infections. A retrospective study was performed at 22 hospitals in Italy (June 2016–March 2018). All adult patients treated with ≥4 days of C/T were enrolled. Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to P. aeruginosa infection and lack of microbiological evidence of infection. C/T treatment was documented in 101 patients with diverse infections, including nosocomial pneumonia (31.7%), acute bacterial skin and skin-structure infection (20.8%), complicated UTI (13.9%), complicated IAI (12.9%), bone infection (8.9%) and primary bacteraemia (5.9%). Over one-half of P. aeruginosa strains were XDR (50.5%), with 78.2% of isolates resistant to at least one carbapenem. C/T was used as first-line therapy in 39 patients (38.6%). When used as second-line or later, the most common reasons for discontinuation of previous antibiotics were in vitro resistance of P. aeruginosa and clinical failure of previous therapy. Concomitant antibiotics were reported in 35.6% of patients. C/T doses were 1.5 g q8h in 70 patients (69.3%) and 3 g q8h in 31 patients (30.7%); median duration of C/T therapy was 14 days. Overall clinical success was 83.2%. Significant lower success rates were observed in patients with sepsis or receiving continuous renal replacement therapy (CRRT). Mild adverse events were reported in only three patients. C/T demonstrated a favourable safety and tolerability profile regardless of the infection type. Clinicians should be aware of the risk of clinical failure with C/T therapy in septic patients receiving CRRT.