José Luis del Pozo

From Clinical Microbiology to Infection Pathogenesis: How Daring To Be Different Works for Staphylococcus lugdunensis

SUMMARY Staphylococcus lugdunensis has gained recognition as an atypically virulent pathogen with a unique microbiological and clinical profile. S. lugdunensis is coagulase negative due to the lack of production of secreted coagulase, but a membrane-bound form of the enzyme present in some isolates can result in misidentification of the organism as Staphylococcus aureus in the clinical microbiology laboratory. S. lugdunensis is a skin commensal and an infrequent pathogen compared to S. aureus and S. epidermidis, but clinically, infections caused by this organism resemble those caused by S. aureus rather than those caused by other coagulase-negative staphylococci. S. lugdunensis can cause acute and highly destructive cases of native valve endocarditis that often require surgical treatment in addition to antimicrobial therapy. Other types of S. lugdunensis infections include abscess and wound infection, urinary tract infection, and infection of intravascular catheters and other implanted medical devices. S. lugdunensis is generally susceptible to antimicrobial agents and shares CLSI antimicrobial susceptibility breakpoints with S. aureus. Virulence factors contributing to this organisms heightened pathogenicity remain largely unknown. Those characterized to date suggest that the organism has the ability to bind to and interact with host cells and to form biofilms on host tissues or prosthetic surfaces.

Prosthetic joint infection: diagnosis and management

Prosthetic joint implantations improve patients’ quality of life but are associated with complications, including aseptic failure and prosthetic joint infection (PJI). Biofilms are the essential factor in the persistence of infection. Early postoperative and acute hematogenous infections are usually easily diagnosed; however, late chronic infections are challenging to predict. Joint aspiration with differential cell counts appears to be a very useful test. New microbiological techniques (i.e., implant sonication and molecular studies) are promising tools. Main objectives of treatment are to alleviate pain, to restore the function and to eradicate the infection. In deciding the best approach for an individual patient, several factors should be considered: the type of the infection, presence of loosening, functional prognosis, etiology and the patient’s preferences. Antimicrobial therapy should be coherent with the chosen surgical strategy. Level of evidence in the field of PJI is low, and recommendations are based on short literature series, experimental data and expert experience.

Effectiveness of the antibiotic lock therapy for the treatment of port-related enterococci, Gram-negative, or Gram-positive bacilli bloodstream infections

OBJECTIVE The purpose of this study is to evaluate the efficacy of antibiotic lock therapy to treat port-related enterococci, Gram-negative, or Gram-positive bacilli bloodstream infections. PATIENTS AND METHODS We conducted a prospective observational study including all patients with port-related bacteremia diagnosed at the Clinica Universitaria de Navarra, Pamplona, Spain. During a 36-month period, 110 patients were diagnosed with port-related bacteremia. Of these patients, 18 met criteria to be enrolled in the study. They were treated with a combination of systemic and antibiotic lock therapy (12-24 h/day during 7-14 days). Treatment effectiveness was assessed by clinical and microbiologic criteria. RESULTS Treatment was associated with clinical and microbiologic success in 88.8% of our patients (2/2 of the Propionibacterium acnes, 5/5 of the Corynebacterium spp., 6/7 of the Gram-negative bacillus, and 3/4 of the Enterococcus faecium port-related bloodstream infections). Mean increase of port life span for all patients after bacteremia was 288 days (range, 0-1403 days). CONCLUSION Antibiotic lock therapy combined with systemic antibiotics appears to be a safe and effective treatment of port-related bacteremia caused by enterococci, Gram-negative, or Gram-positive bacilli if the patient is stable and no septic syndrome is associated.

Antifungal activity against Candida biofilms

Candida species have two distinct lifestyles: planktonic, and surface-attached communities called biofilms. Mature C. albicans biofilms show a complex three-dimensional architecture with extensive spatial heterogeneity, and consist of a dense network of yeast, hyphae, and pseudohyphae encased within a matrix of exopolymeric material. Several key processes are likely to play vital roles at the different stages of biofilm development, such as cell-substrate and cell-cell adherence, hyphal development, and quorum sensing. Biofilm formation is a survival strategy, since biofilm yeasts are more resistant to antifungals and environmental stress. Antifungal resistance is a multifactorial process that includes multidrug efflux pumps, target proteins of the ergosterol biosynthetic pathway. Most studies agree in presenting azoles as agents with poor activity against Candida spp. biofilms. However, recent studies have demonstrated that echinocandins and amphotericin B exhibit remarkable activity against C. albicans and Candida non-albicans biofilms. The association of Candida species with biofilm formation increases the therapeutic complexity of foreign body-related yeast infections. The traditional approach to the management of these infections has been to explant the affected device. There is a strong medical but also economical motivation for the development of novel anti-fungal biofilm strategies due to the constantly increasing resistance of Candida biofilms to conventional antifungals, and the high mortality caused by related infections. A better description of the extent and role of yeast in biofilms may be critical for developing novel therapeutic strategies in the clinical setting.

Granulicatella adiacens breast implant-associated infection

The 1st reported case of breast implant-associated infection due to Granulicatella adiacens, formerly known as nutritionally variant streptococci, Streptococcus adiacens, and Abiotrophia adiacens is presented. Microbiology and previously reported cases of infections by this organism are reviewed.

Effect of amphotericin B alone or in combination with rifampicin or clarithromycin against Candida species biofilms.

Effectiveness of amphotericin B alone or in combination with rifampicin or clarithromycin on the killing of Candida species biofilms was investigated in vitro. Amphotericin B was assayed at 0.005 to 10 mg/ml. Rifampin and clarithromycin were assayed at 10 mg/ml. We studied 7 Candida albicans, 3 Candida parapsilosis, 3 Candida glabrata, 3 Candida krusei and 2 Candida tropicalis strains. Biofilms were developed in 96-well, flat-bottomed microtiter plates for 48 hours. A synergistic effect between amphotericin B and clarithromycin was demonstrated against 66.6% of C. parapsilosis, 66.6% of C. glabrata, and 42.8% of C. albicans biofilms. A synergistic effect between amphotericin B and rifampin was demonstrated against 66.6% of C. parapsilosis, 42.8% of C. albicans, and 33.3% of C. glabrata biofilms. No synergistic effect was observed against C. krusei or C. tropicalis biofilms with any of the combinations. Rifampin or clarithromycin alone did not exert any effect on Candida species biofilms. Rifampin or clarithromycin combinations with amphotericin B might be of interest in the treatment of Candida biofilm-related infections.

Cancer and the microbiome: potential applications as new tumor biomarker

Microbial communities that colonize in humans are collectively described as microbiome. According to conservative estimates, about 15% of all types of neoplasms are related to different infective agents. However, current knowledge is not sufficient to explain how the microbiome contributes to the growth and development of cancers. Large and thorough studies involving colonized, diverse and complex microbiome entities are required to identify microbiome as a potential cancer marker and to understand how the immune system is involved in response to pathogens. This article reviews the existing evidence supporting the enigmatic association of transformed microbiome with the development of cancer through the immunological modification. Ascertaining the connection between microbiome and immunological responses with risk of cancer may direct to explaining significant advances in the etiology of cancer, potentially disclosing a novel paradigm of research for the management and prevention of cancer.

Primers on Molecular Pathways: Lipopolysaccharide Signaling - Potential Role in Pancreatitis and Pancreatic Cancer

The innate immune system recognizes the presence of bacterial pathogens through the expression of a family of membrane receptors known as Toll-like receptors (TLRs). Lipopolysaccharide (LPS) is specifically recognized by TLR4. Recognition of microbial components by TLRs initiates signal transduction pathways, which triggers expression of genes. These gene products control innate immune responses and further instruct development of antigen-specific acquired immunity. TLR signaling pathways are finely regulated by TIR domain-containing adaptors, such as MyD88, TIRAP/Mal, TRIF and TRAM. LPS can act not only on immune cells but also on some types of epithelial cells including cancer cells and promote its transformed phenotype. Specifically, LPS can activate NF-kappaB signaling in pancreatic cancer cells, thus connecting inflammation with cancer progression. The TLR4 signaling pathway may offer a useful therapeutic target for patients with pancreatitis or pancreatic cancer associated with inflammation.The innate immune system recognizes the presence of bacterial pathogens through the expression of a family of membrane receptors known as Toll-like receptors (TLRs). Lipopolysaccharide (LPS) is specif

Prolonged use of tedizolid in a pulmonary non-tuberculous mycobacterial infection after linezolid-induced toxicity.

References 1 Falk L, Fredlund H, Jensen JS. Symptomatic urethritis is more prevalent in men infected with Mycoplasma genitalium than with Chlamydia trachomatis. Sex Transm Infect 2004; 80: 289–93. 2 Lis R, Rowhani-Rahbar A, Manhart L. Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis. Clin Infect Dis 2015; 61: 418–26. 3 Jensen JS, Cusini M, Gomberg M et alet al. 2016 European guideline on Mycoplasma genitalium infections. J Eur Acad Dermatol Venereol 2016; doi:10.1111/jdv.13849. 4 Lau A, Bradshaw CS, Lewis D et alet al. The efficacy of azithromycin for the treatment of genital Mycoplasma genitalium: a systematic review and metaanalysis. Clin Infect Dis 2015; 61: 1389–99. 5 Couldwell DL, Tagg KA, Jeoffreys NJ et alet al. Failure of moxifloxacin treatment in Mycoplasma genitalium infections due to macrolide and fluoroquinolone resistance. Int J STD AIDS 2013; 24: 822–8. 6 Bissessor M, Tabrizi SN, Twin J et alet al. Macrolide resistance and azithromycin failure in a Mycoplasma genitalium-infected cohort and response of azithromycin failures to alternative antibiotic regimens. Clin Infect Dis 2015; 60: 1228–36. 7 Mena LA, Mroczkowski TF, Nsuami M et alet al. A randomized comparison of azithromycin and doxycycline for the treatment of Mycoplasma genitalium-positive urethritis in men. Clin Infect Dis 2009; 48: 1649–54. 8 Björnelius E, Anagrius C, Bojs G et alet al. Antibiotic treatment of symptomatic Mycoplasma genitalium infection in Scandinavia: a controlled clinical trial. Sex Transm Infect 2008; 84: 72–6. 9 Falk L, Enger M, Jensen JS. Time to eradication of Mycoplasma genitalium after antibiotic treatment in men and women. J Antimicrob Chemother 2015; 70: 3134–40.

Travel and fake artesunate: a risky business

Division of Internal Medicine (C J Chaccour MD), and Division of Infectious Diseases, Department of Medicine (C J Chaccour, J L Del Pozo MD), and Division of Clinical Microbiology and Parasitology (J L Del Pozo), Clinica Universidad de Navarra, Pamplona, Spain; and Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK (Prof D Mabey PhD, H Kaur PhD)