Influence of fluoroquinolones on phagocytosis and killing of<i>Candida albicans</i>by human polymorphonuclear neutrophils

Grüger, Thomas; Mörler, Caroline; Brandenburg, Kerstin; Nidermajer, S.; Horré, R.; Zündorf, Josef

doi:10.1080/13693780802017535

Cited by 8 publications

(23 citation statements)

References 48 publications

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“…These data confirm that CIP and probably other fluoroquinolones (such as moxifloxacin, prulifloxacin, pefloxacin, and sparfloxacin) can help the host defense in the outcome of infections because they accumulate and remain active inside PMNs (20,(24)(25)(26).…”

Section: Discussionsupporting

confidence: 67%

Key Roles of Human Polymorphonuclear Cells and Ciprofloxacin in Lactobacillus Species Infection Control

Mandras

Tullio

Furneri

et al. 2016

Antimicrob Agents Chemother

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Lactobacilli have the potential to act as reservoirs of antibiotic resistance genes similar to those found in human pathogens, with the risk of transferring these genes to many pathogenic bacteria. In this study, we investigated the role of human polymorphonuclear cells (PMNs) against Lactobacillus spp. both resistant and susceptible to ciprofloxacin (a fluoroquinolone) and the effect of ciprofloxacin on the interaction between PMNs and three Lactobacillus spp. with different patterns of susceptibility to this drug. Hence, the primary functions of PMNs, such as phagocytosis and bacterial intracellular killing, against lactobacilli were investigated. The rate of PMN phagocytosis was high for ciprofloxacin-sensitive and ciprofloxacin-resistant strains. The patterns of intracellular killing of ciprofloxacin-sensitive and ciprofloxacin-resistant strains by PMNs underline that PMNs alone were able to kill lactobacilli. The addition of ciprofloxacin to PMNs did not result in a significant increase in the bacterial uptake by phagocytes. On the contrary, ciprofloxacin had a marked effect on PMN intracellular killing, resulting in increased numbers of killed ciprofloxacin-sensitive bacteria in comparison with antibiotic-free controls. Our data show that by itself, the profile of antibiotic resistance does not constitute an intrinsic factor of greater or lesser pathogenicity toward the host. The ability of PMNs to kill a diverse array of bacterial pathogens is essential for human innate host defense, primarily in immunocompromised patients. Lactobacillus spp., considered nonpathogenic bacteria of the human gastrointestinal and vaginal microbiotas, are widely used as probiotics in dairy products. Moreover, they can positively interact with other microorganisms of the human microbiota (1).Infections caused by lactobacilli are extremely rare; however, they can spread into the blood and cause serious clinical infections (2, 3). Many investigators have demonstrated that lactobacilli have a high natural resistance to many antimicrobial drugs, such as fluoroquinolones, e.g., ciprofloxacin (CIP) (4-7); our recent studies showed that the mechanism of resistance to fluoroquinolones could be associated with the presence of a NorA-like efflux pump found in ciprofloxacin-resistant (CIP r ) strains of L. fermentum isolated from the human oral cavity (8).For several decades, studies on selection and dissemination of antibiotic resistance have focused mainly on clinically relevant species. The magnitude of the problem is significantly increased by the ability of bacteria to transfer resistance horizontally and by the mounting increase in the overuse and misuse of antibiotics, which has created an enormous selective pressure toward resistant bacteria.Gene transfer occurs widely in vivo between pathogenic and commensal bacteria of the human microbiota, as identical resistance genes are present in several bacterial species from different hosts. Lactobacilli have the potential to act as reservoirs of antibiotic resistance genes similar to th...

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Section: Discussionsupporting

confidence: 67%

Key Roles of Human Polymorphonuclear Cells and Ciprofloxacin in Lactobacillus Species Infection Control

Mandras

Tullio

Furneri

et al. 2016

Antimicrob Agents Chemother

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“…For example, sulfonamides were shown to have both inhibitory and stimulatory effects on the host response against Candida spp. (7, 16), whereas fluoroquinolones had no effect at therapeutic concentrations (10).…”

Section: Discussionmentioning

confidence: 99%

Antibiotic Exposure as a Risk Factor for Fluconazole-Resistant Candida Bloodstream Infection

Ben‐Ami

Olshtain‐Pops

Krieger

et al. 2012

Antimicrob Agents Chemother

150

112

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Candida species have emerged as frequent causes of nosocomial bloodstream infection (BSI) in association with well-defined risk factors, including prolonged hospitalization, abdominal surgery, antibiotic treatment, neutropenia and central venous catheterization (14). Candidemia is associated with high rates of attributable mortality, prolongation of hospital stay, and excessive costs (28). In recent years, there has been a shift in the distribution of Candida species causing invasive infection, with non-albicans species now surpassing Candida albicans in many institutions (14,25). Of particular concern is the rising incidence of the azolenonsusceptible species C. glabrata and the inherently fluconazoleresistant species C. krusei (11,25,27).Fluconazole is often used as empirical treatment of candidemia. However, given the correlation between the survival rate and the timely initiation of appropriate treatment for candidemia (8), accurate assessment of the risk of fluconazole-resistant Candida (FRC) BSI is of prime importance. Patients who were recently treated with an azole drug are at increased risk of infection with FRC (9) and should be treated initially with an echinocandin agent according to current guidelines (18). However, experimental and clinical data support the notion that nonantifungal antimicrobial agents also affect the risk of colonization and infection with FRC (15,17,22). Since exposure to antibacterial drugs among at-risk patients far exceeds exposure to antifungal agents, even modest effects of individual antibacterials could translate into significant overall changes in the susceptibility patterns of Candida spp. Nevertheless, the collateral effects of antibacterial drugs on Candida spp. are poorly understood. To address this question, we analyzed prospectively collected data from a nationwide study of candidemia in Israel and examined the association between exposure to antifungal and antibacterial agents and the risk of infection with FRC. MATERIALS AND METHODS Study design.We performed a prospective nationwide study of candidemia in Israel from November 2005 through June 2007. Eighteen medical centers, which together account for 75% of the hospital beds in Israel, were included. All candidemia episodes that occurred in the participating centers during the study period were eligible for inclusion in this study. Clinical data were prospectively entered into standardized data forms by on-site investigators at each of the centers. The Candida sp. clinical isolates underwent preliminary identification and susceptibility testing in each center according to local practices. Subsequently, the isolates were transferred together with the corresponding data forms to the central study site, where species identification and susceptibility testing were performed as detailed below. The data forms were collected by the study coordinator, reviewed by the principal investigator, and entered into a computerized database. The study was approved by the ethics committee of each of the participating centers.Data...

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“…Instrument settings [linear parameters for forward scatter (FSC) and side scatter (SSC), logarithmic parameters for FL1 and FL2] with the best test performance turned out to be very similar to those used previously for experiments with Candida albicans [19]. Briefly, PMN were selectively analysed by gating them according to their FSC and SSC characteristics.…”

Section: Methodsmentioning

confidence: 99%

Negative Impact of Linezolid on Human Neutrophil Functions in vitro

Grüger¹,

Schmidt²,

Nidermajer³

et al. 2012

Chemotherapy

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Background/Aims: In a recent phase III clinical trial on linezolid, more patients in the linezolid treatment arm acquired Gram-negative catheter-related bloodstream infections despite the adequate therapy of infections caused by Gram-negative bacteria. We tested our hypothesis that linezolid impairs phagocytosis and the killing of Gram-negative bacteria by polymorphonuclear leukocytes (PMN). Methods: The influence of clinically relevant concentrations (5, 20 and 50 mg/l) of linezolid on granulocyte function in vitro was tested. Phagocytosis was determined by flow cytometry, and killing of bacteria was evaluated by plate counting. Chemotaxis was examined by an under-agarose cell migration assay. Gram-positive and Gram-negative bacteria were used. Results: Linezolid significantly impaired phagocytosis of a specific Escherichia coli strain in a concentration-dependent manner, whereas the effect on Pseudomonas aeruginosa was less prominent. No such effects were observed with a different E. coli strain or Staphylococcus aureus. Neither killing nor the chemotactic behaviour of PMN was significantly affected by linezolid. Conclusions: The observed concentration-dependent impairment of the phagocytic function might contribute to the higher frequency of catheter-related Gram-negative bloodstream infections in patients treated with linezolid. Individual patient risk may also depend on the causative Gram-negative strain.

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Influence of fluoroquinolones on phagocytosis and killing ofCandida albicansby human polymorphonuclear neutrophils

Cited by 8 publications

References 48 publications

Key Roles of Human Polymorphonuclear Cells and Ciprofloxacin in Lactobacillus Species Infection Control

Key Roles of Human Polymorphonuclear Cells and Ciprofloxacin in Lactobacillus Species Infection Control

Antibiotic Exposure as a Risk Factor for Fluconazole-Resistant Candida Bloodstream Infection

Negative Impact of Linezolid on Human Neutrophil Functions in vitro

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