Epidemiology of Mucormycosis in Greece; Results from a Nationwide Prospective Survey and Published Case Reports.

Mucormycosis has emerged as a group of severe infections mainly in immunocompromised patients. We analysed the epidemiology of mucormycosis in Greece in a multicentre, nationwide prospective survey of patients of all ages, during 2005-2022. A total of 108 cases were recorded. The annual incidence declined after 2009 and appeared stable thereafter, at 0.54 cases/million population. The most common forms were rhinocerebral (51.8%), cutaneous (32.4%), and pulmonary (11.1%). Main underlying conditions were haematologic malignancy/neutropenia (29.9%), haematopoietic stem cell transplantation (4.7%), diabetes mellitus (DM) (15.9%), other immunodeficiencies (23.4%), while 22.4% of cases involved immunocompetent individuals with cutaneous/soft-tissue infections after motor vehicle accident, surgical/iatrogenic trauma, burns, and injuries associated with natural disasters. Additionally, DM or steroid-induced DM was reported as a comorbidity in 21.5% of cases with various main conditions. Rhizopus (mostly R. arrhizus) predominated (67.1%), followed by Lichtheimia (8.5%) and Mucor (6.1%). Antifungal treatment consisted mainly of liposomal amphotericin B (86.3%), median dose 7 mg/kg/day, range 3-10 mg/kg/day, with or without posaconazole. Crude mortality was 62.8% during 2005-2008 but decreased significantly after 2009, at 34.9% (p = 0.02), with four times fewer haematological cases, fewer iatrogenic infections, and fewer cases with advanced rhinocerebral form. The increased DM prevalence should alert clinicians for timely diagnosis of mucormycosis in this patient population.

Global Cutaneous Mucormycosis: A Systematic Review.

Cutaneous mucormycosis is the third most common clinical type of mucormycosis. The signs and symptoms vary widely, and it is important to make the diagnosis as early as possible in order to achieve a better outcome. We present a systematic review of its epidemiology, clinical presentation, diagnosis, and treatment, analyzing cases published from 1958 until 2021. The review was conducted according to the PRISMA guidelines and included 693 cases from 485 articles from 46 countries. Most publications were from North America (256 cases, 36.9%) and Asia (216 cases, 31.2%). The most common risk factors were diabetes mellitus (20%) and hematological malignancies (15.7%). However, a large proportion of published cases (275, 39.6%) had no identified underlying disease. The most common mode of transmission was trauma (54%), and 108 (15.6%) cases were healthcare-associated. In this review, 291 (42.5%) patients had localized infection, and 90 (13%) had disseminated mucormycosis. In Europe, N. America and S. America, the most common genus was Rhizopus spp., while in Asia it was Apophysomyces spp. (34.7%). Treatment was performed with antifungals, mainly amphotericin B, and/or surgery. Mortality was significantly lower when both antifungals and surgery were applied (29.6%).

Management of Invasive Fungal Infections in Adult Patients with Hematological Malignancies in Greece during the Financial Crisis: Challenges and Recommendations.

There are concerns that the financial crisis in Greece negatively affected the management of invasive fungal infections (IFIs) among patients with hematological malignancies (HM). A working group (WG) was formed to explore the situation and make recommendations. A questionnaire was created and distributed to physicians caring for patients with HM, to gather information in a standardized manner on prescribing physicians, patient characteristics, availability of diagnostics, antifungal treatment practices and the conditions and particularities of Greek hospitals. A total of 141 physicians from 36 hematology units and laboratories located in 26 Greek hospitals participated. Regarding hospitalization conditions, only 56% reported that their patients were treated in isolated single or double bed rooms, 22% reported availability of HEPA filters, 47% reported construction works in progress, and an alarming 18% reported the presence of birds on open windows. Regarding diagnosis, only 31% reported availability of biomarkers for diagnosis of IFIs, 76% reported that CT scans were performed in a timely fashion, 42% reported prompt availability of broncho-alveolar lavage, and only 6% availability of therapeutic drug monitoring. Of concern, 26% of the responders reported non-availability of some antifungals. In conclusion, significant challenges exist for the optimal management of IFIs in patients with HM in Greece.

Fungal infections in patients with inflammatory bowel disease: A systematic review.

BACKGROUND: Despite reports of fungal infections in patients with inflammatory bowel disease (IBD), their clinical and microbiological characteristics remain unknown. OBJECTIVES: The aim of this systematic review was to examine all available evidence regarding fungal infections in patients with IBD. METHODS: Systematic search of PubMed (through 27 May 2017) for studies providing data on clinical, microbiological, treatment and outcome data of fungal infections in patients with IBD. The primary study outcome was to record the most common fungal species in patients with IBD. Secondary outcomes were classified into 3 categories: (i) characteristics of fungal infections; (ii) data on IBD and (iii) treatment and outcomes of fungal infections in patients with IBD. RESULTS: Fourteen studies with data on 1524 patients were included in final analysis. The most common fungal infections in patients with IBD were caused by Candida species (903 infections); the most commonly reported site of Candida infection was the gastrointestinal tract. Available evidence shows that most fungal infections occur within 12 months of IBD treatment and within 6 months when anti-TNFa agents are used. CONCLUSIONS: This systematic review thoroughly describes fungal infections in patients with IBD and provides important information for the early detection and management of these infections.

'Prostate Abscess' as the Initial Manifestation of Granulomatosis with Polyangiitis (Wegener's Granulomatosis).

Prostatic involvement in granulomatosis with polyangiitis (GWP), formerly known as Wegener's granulomatosis, is rare, mostly arising in the context of systemic involvement. Prostatic involvement as the first manifestation of this systemic disease is exceptionally rare. We hereby present the case of a 41-year-old male patient who underwent transurethral prostate resection for what was initially diagnosed as suppurative, focally necrotizing prostatitis. Prolonged postoperative fever that did not respond to various treatments, as well as the subsequent appearance of a left pleural effusion, a left upper pulmonary lobe lesion and cutaneous nodules, led to a reevaluation of histological slides which, along with the determination of serum c-ANCA/anti-PR3 antibody levels, established the diagnosis of GWP. Physicians, and especially urologists and infectious diseases specialists, should be aware of this rare association and consider GWP in the event of nonresolving prostatitis, especially when characteristic symptoms from other systems appear.

The association between colonization with carbapenemase-producing enterobacteriaceae and overall ICU mortality: an observational cohort study.

OBJECTIVES: Infections caused by carbapenemase-producing Enterobacteriaceae are increasing worldwide, especially in ICUs, and have been associated with high mortality rates. However, unequivocally demonstrating causality of such infections to death is difficult in critically ill patients because of potential confounding and competing events. Here, we quantified the effects of carbapenemase-producing Enterobacteriaceae carriage on patient outcome in two Greek ICUs with carbapenemase-producing Enterobacteriaceae endemicity. DESIGN: Observational cohort study. SETTING: Two ICUs with carbapenemase-producing Enterobacteriaceae endemicity. PATIENTS: Patients admitted to the ICU with an expected length of ICU stay of at least 3 days were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Carbapenemase-producing Enterobacteriaceae colonization was established through screening in perineum swabs obtained at admission and twice weekly and inoculated on chromogenic plates. Detection of carbapenemases was performed phenotypically, with confirmation by polymerase chain reaction. Risk factors for ICU mortality were evaluated using cause-specific hazard ratios and subdistribution hazard ratios, with carbapenemase-producing Enterobacteriaceae colonization as time-varying covariate. One thousand seven patients were included, 36 (3.6%) were colonized at admission, and 96 (9.5%) acquired carbapenemase-producing Enterobacteriaceae colonization during ICU stay, and 301 (29.9%) died in ICU. Of 132 carbapenemase-producing Enterobacteriaceae isolates, 125 (94.7%) were Klebsiella pneumoniae and 74 harbored K. pneumoniae carbapenemase (56.1%), 54 metallo-ß-lactamase (40.9%), and four both (3.0%). Carbapenemase-producing Enterobacteriaceae colonization was associated with a statistically significant increase of the subdistribution hazard ratio for ICU mortality (subdistribution hazard ratio=1.79; 95% CI, 1.31-2.43), not explained by an increased daily hazard of dying (cause-specific hazard ratio for death=1.02; 95% CI, 0.74-1.41), but by an increased length of stay (cause-specific hazard ratio for discharge alive=0.73; 95% CI, 0.51-0.94). Other risk factors in the subdistribution hazard model were Acute Physiology and Chronic Health Evaluation II score (subdistribution hazard ratio=1.13; 95% CI, 1.11-1.15), female gender (subdistribution hazard ratio=1.29; 95% CI, 1.02-1.62), presence of solid tumor (subdistribution hazard ratio=1.54; 95% CI, 1.15-2.06), hematopoietic malignancy (subdistribution hazard ratio=1.61; 95% CI, 1.04-2.51), and immunodeficiency (subdistribution hazard ratio=1.59; 95% CI, 1.11-2.27). CONCLUSIONS: Patients colonized with carbapenemase-producing Enterobacteriaceae have on average a 1.79 times higher hazard of dying in ICU than noncolonized patients, primarily because of an increased length of stay.

Rhodotorula mucilaginosa associacted meningitis: A subacute entity with high mortality. Case report and review.

A fatal case of meningitis due to Rhodotorula mucilaginosa in a 28 year-old HIV-negative male with a history of Hodgkin lymphoma who underwent salvage chemotherapy is presented. Reviewing the literature we identified 13 cases with central nervous system infection due Rhodotorula spp. The disease usually occurs in HIV negative immunosupressed middle-aged males. It takes the form of subacute or chronic meningitis accompanied by fever with an overall mortality of 46.2% despite antifungal therapy.

Breakthrough candidaemia caused by phenotypically susceptible Candida spp. in patients with haematological malignancies does not correlate with established interpretive breakpoints.

In a study of 27,864 patients with haematological malignancies, 40 patients with candidaemia were identified, among whom 21 developed candidaemia while receiving systemic antifungal therapy [breakthrough candidaemia (BTC)]. Demographic, clinical, microbiological and molecular features of these episodes were analysed. Compared with 19 patients with de novo candidaemia, patients with BTC were more likely to have neutropenia (81% vs. 63%), longer median duration of neutropenia (27 days vs. 15 days), hypogammaglobulinaemia (62% vs. 37%) and central venous catheters (CVCs) (86% vs. 68%). The median duration of prior antifungal exposure was 46 days (range 3-108 days). Among the 18 available Candida spp. isolates, 15 (83%) were phenotypically susceptible to the antifungal agent that the patient was receiving. Emergence of resistance was the mechanism leading to BTC in three cases of patients receiving echinocandins. Other possible mechanisms of BTC were (i) elevated (≥2) minimum lethal concentration/minimum inhibitory concentration (MLC/MIC) ratio (reduced ability for a fungicidal agent to kill a fungal pathogen) in all patients receiving amphotericin B and (ii) elevated MLC/MIC ratios in all Candida parapsilosis isolates with MICs≤1 µg/mL to echinocandins. DNA sequencing of the hotspot 1 region of the fks1 and fks2 genes in seven different isolates of C. parapsilosis group demonstrated P660A in Fks1 but no polymorphisms in fks2. In conclusion, mechanisms for BTC in the setting of prolonged neutropenia may be host-based (hypogammaglobulinaemia and CVC) and pathogen-based. CLSI interpretive breakpoints do not reliably predict BTC in patients with haematological malignancies and warrant further investigation.

Prescription of antibiotics and knowledge about antibiotic costs among physicians working in tertiary-care hospitals.

The objective of this study is to investigate antibiotic prescription practices among hospital-based physicians in Greece, using the 2007 national guidelines as the golden standard. A total of 168 physicians participated. Compliance rate with the first-line antibiotic treatment recommended by the national guidelines was 65·5% for acute bacterial sinusitis; 24% for acute uncomplicated cystitis; 36·4% for an acute febrile diarrheic syndrome; 38% for an afebrile adult with chronic obstructive pulmonary disease and non-productive cough of 7 days duration; 23·2% for streptococcal pharyngotonsillitis; 55·1% for a surgically sutured, dirty wound; and 48·2% for community-acquired pneumonia. The total mean rate of compliance with the first recommended antibiotic was 41·2%.

Cutaneous mucormycosis.

Mucormycosis is an invasive fungal infection caused by fungi of the order Mucorales, mainly affecting immunocompromised patients. Cutaneous mucormycosis is the third most common clinical form of the disease, after pulmonary and rhino-cerebral. The usual factors predisposing to this infection are hematological malignancies and diabetes mellitus, but a significant proportion of patients are immunocompetent. The agents of mucormycosis are ubiquitous in nature and are transmitted to the skin by direct inoculation, as a result of various types of trauma. These include needle sticks, stings and bites by animals, motor vehicle accidents, natural disasters, and burn injuries. The typical presentation of mucormycosis is the necrotic eschar, but it can present with various other signs. The infection can be locally invasive and penetrate into the adjacent fat, muscle, fascia, and bone, or become disseminated. Diagnosis is difficult because of the nonspecific findings of mucormycosis. Biopsy and culture should be performed. The treatment of mucormycosis is multimodal and consists of surgical debridement, use of antifungal drugs (amphotericin B and posaconazole), and reversal of underlying risk factors, when possible. Mortality rates, although lower than in other forms of the disease, are significant, ranging from 4% to 10% when the infection is localized.

Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3).

Mucormycosis is an emerging cause of infectious morbidity and mortality in patients with hematologic malignancies. However, there are no recommendations to guide diagnosis and management. The European Conference on Infections in Leukemia assigned experts in hematology and infectious diseases to develop evidence-based recommendations for the diagnosis and treatment of mucormycosis. The guidelines were developed using the evidence criteria set forth by the American Infectious Diseases Society and the key recommendations are summarized here. In the absence of validated biomarkers, the diagnosis of mucormycosis relies on histology and/or detection of the organism by culture from involved sites with identification of the isolate at the species level (no grading). Antifungal chemotherapy, control of the underlying predisposing condition, and surgery are the cornerstones of management (level A II). Options for first-line chemotherapy of mucormycosis include liposomal amphotericin B and amphotericin B lipid complex (level B II). Posaconazole and combination therapy of liposomal amphotericin B or amphotericin B lipid complex with caspofungin are the options for second line-treatment (level B II). Surgery is recommended for rhinocerebral and skin and soft tissue disease (level A II). Reversal of underlying risk factors (diabetes control, reversal of neutropenia, discontinuation/taper of glucocorticosteroids, reduction of immunosuppressants, discontinuation of deferroxamine) is important in the treatment of mucormycosis (level A II). The duration of antifungal chemotherapy is not defined but guided by the resolution of all associated symptoms and findings (no grading). Maintenance therapy/secondary prophylaxis must be considered in persistently immunocompromised patients (no grading).

Incidence and risk factors for central vascular catheter-related bloodstream infections in a tertiary care hospital.

This study evaluated the incidence of colonization and infection related to Central Vascular Catheters (CVC) in a tertiary care Greek hospital, as well as risk factors associated with catheter-related bloodstream infection (CRBSI). A total of 340 CVCs, were studied in relation to patient clinical and epidemiological data, CVC characteristics, and microbiological culture results. Risk factors were assessed. Pulsed field gel electrophoresis was used for the investigation of the clonal relationship of the isolates. The incidence for CRBSI and catheter colonization (CC) was 11.47 and 19.49 per 1,000 catheter days, respectively. Risk factors independently associated with CRBSI were use of corticosteroids, diabetes mellitus, solid organ neoplasm, long duration of catheterization, and changing the CVC dressing at intervals of 48 hours or more. Risk factors for CC were diabetes mellitus, hospitalization in ICU, and prolonged hospitalization. The predominant microorganisms isolated from CRBSI episodes were coagulase-negative staphylococci. All patients with CVC require constant infection surveillance and appropriate care by trained medical staff. Use of CVC for the shortest time possible, good hand hygiene and change of CVC dressing at intervals of less than 48 hours are infection prevention practices that need to be followed.

Global epidemiology of cutaneous zygomycosis.

The large majority of cases reported worldwide as zygomycosis are infections caused by fungi belonging to the order Mucorales. These infections are invasive, often lethal, and they primarily affect immunocompromised patients. Cutaneous zygomycosis is the third most common clinical presentation, after sinusitis and pulmonary disease. Most patients with cutaneous zygomycosis have underlying diseases, such as hematological malignancies and diabetes mellitus, or have received solid organ transplantation, but a large proportion of these patients are immunocompetent. Trauma is an important mode of acquiring the disease. The disease can be very invasive locally and penetrate from the cutaneous and subcutaneous tissues into the adjacent fat, muscle, fascia, and bone. The diagnosis of cutaneous zygomycosis is often difficult because of the nonspecific findings of the infection. The clinician must have a high degree of suspicion and use all available diagnostic tools, because early diagnosis leads to an improved outcome. The treatment of zygomycosis is multimodal and consists of surgical debridement, use of antifungal drugs, and reversal of underlying risk factors, when possible. The main antifungal drug used in the treatment of zygomycosis is amphotericin B. Posaconazole is sometimes used for salvage treatment, as continuation of treatment after initial administration of amphotericin B, or in combination. The mortality of cutaneous zygomycosis is lower in comparison with other forms of the disease, but it is still significant. When the disease is localized, mortality still ranges from 4% to 10%.

Mecillinam/clavulanate combination: a possible option for the treatment of community-acquired uncomplicated urinary tract infections caused by extended-spectrum ß-lactamase-producing Escherichia coli.

BACKGROUND: Extended-spectrum ß-lactamases (ESBLs) have emerged as an important mechanism of ß-lactam resistance among community uropathogens. We characterized the ESBLs of a collection of Escherichia coli isolates recovered from outpatients with urinary tract infection during nationwide surveillance conducted from 2005 to 2006 in Greece, and evaluated the in vitro activity of mecillinam and mecillinam/clavulanate against them. MATERIALS AND METHODS: ESBLs were characterized with PCR and sequencing. In vitro interactions were evaluated with agar dilution with and without clavulanate (4 mg/L) using an inoculum of 10(4) or 10(6) cfu/spot as well as with time-kill methodology. RESULTS: Among 48 ESBL producers, 47 (97.9%) were susceptible to mecillinam. CTX-M-type enzymes were produced by 87.2%, with CTX-M-3 being the most prevalent. SHV enzymes were found in 10.6%, VEB enzymes in 2.1%, TEM enzymes in 19.2% and OXA-type enzymes in 12.8%. Synergy with clavulanate was detected in 60.4% using the agar dilution method and in 43.8% using the time-kill methodology. An inoculum effect was detected in 64.6% of isolates, but this phenomenon was inverted and synergy was evidenced for 85.4% with clavulanate. When a high inoculum was used, 60.4% (29/48) were resistant to mecillinam, but 97.9% (47/48) were susceptible in the presence of clavulanate. CONCLUSIONS: CTX-M-type enzymes were the most prevalent among ESBL-producing E. coli uropathogens in Greece. Mecillinam may be useful in uncomplicated cystitis caused by ESBL producers with low MICs. The addition of the inhibitor could improve and extend the activity of mecillinam, even in the setting of infection with a high bacterial inoculum, and merits clinical evaluation.

Epidemiology and clinical manifestations of mucormycosis.

Mucormycosis is an emerging angioinvasive infection caused by the ubiquitous filamentous fungi of the Mucorales order of the class of Zygomycetes. Mucormycosis has emerged as the third most common invasive mycosis in order of importance after candidiasis and aspergillosis in patients with hematological and allogeneic stem cell transplantation. Mucormycosis also remains a threat in patients with diabetes mellitus in the Western world. Furthermore, this disease is increasingly recognized in recently developed countries, such as India, mainly in patients with uncontrolled diabetes or trauma. Epidemiological data on this type of mycosis are scant. Therefore, our ability to determine the burden of disease is limited. Based on anatomic localization, mucormycosis can be classified as one of 6 forms: (1) rhinocerebral, (2) pulmonary, (3) cutaneous, (4) gastrointestinal, (5) disseminated, and (6) uncommon presentations. The underlying conditions can influence clinical presentation and outcome. This review describes the emerging epidemiology and the clinical manifestations of mucormycosis.

Zygomycosis in Immunocompromised non-Haematological Patients.

Zygomycoses caused by fungi of the mucorales order (mucormycoses) are emerging fungal diseases with a high fatality rate. The most important risk factors include neutropenia or functional neutropenia, diabetic ketoacidosis, iron overload, major trauma, prolonged use of corticosteroids, illicit intravenous drug (ID) use, neonatal prematurity, malnourishment, and maybe a previous exposure to antifungal agents with no activity against zygomycetes, such as voriconazole and echinocandins.A high index of suspicion is crucial for the diagnosis, as prompt and appropriate management can considerably reduce morbidity and mortality. Suspicion index can be increased through recognition of the differential patterns of clinical presentation. In the non- haematological immunocompromised patients, mucormycosis can manifest in various clinical forms, depending on the underlying condition: mostly as rhino-orbital or rhino-cerebral in diabetes patients, pulmonary infection in patients with malignancy or solid organ transplantation, disseminated infection in iron overloaded or deferoxamine treated patients, cerebral - with no sinus involvement - in ID users, gastrointestinal in premature infants or malnourishment, and cutaneous after direct inoculation in immunocompetent individuals with trauma or burns.Treating a patient's underlying medical condition and reducing immunosuppression are essential to therapy. Rapid correction of metabolic abnormalities is mandatory in cases such as uncontrolled diabetes, and corticosteroids or other immunosuppressive drugs should be discontinued where feasible. AmphotericinB or its newer and less toxic lipid formulations are the drugs of choice regarding antifungal chemotherapy, while extensive surgical debridement is essential to reduce infected and necrotic tissue. A high number of cases could be prevented through measures including diabetes control programmes and proper pre- and post-surgical hygiene.

Human papillomavirus (HPV) detection using in situ hybridization in histologic samples: correlations with cytologic changes and polymerase chain reaction HPV detection.

Although in situ hybridization (ISH) and polymerase chain reaction (PCR) have extensively been used on cytology specimens, there have been limited reports of the usefulness of these techniques in relation to confirmed histologic findings. In this study, we used PCR and ISH to detect human papillomavirus (HPV) in cytologic and histologic specimens, respectively. By using positive and negative likelihood ratios, we attempted to identify any predictive role of ISH testing alone or in combination with PCR for the development of high-grade histologic lesions (cervical intraepithelial neoplasia [CIN] 2+). In our study, ISH was a useful method for detection of HPV, even in a large fraction of samples with normal cytologic or biopsy findings. We suggest that when used together and evaluated in conjunction with histologic sections, ISH is a useful tool for ancillary molecular testing of HPV infection in cervical lesions, especially in CIN 2+ histological lesions where its analytic sensitivities and specificities were as good as those of PCR testing.

Human herpesvirus 6 infection as a trigger of multiple sclerosis.

We systematically reviewed the existing evidence to determine whether a relationship exists between infection with human herpesvirus 6 (HHV-6) and multiple sclerosis (MS) and, if so, to define the strength of that relationship. The following terms were used in searches of the Entrez-PubMed database (1966-2009): human herpes virus 6, HHV 6, demyelination, multiple sclerosis, pathogenesis, diagnosis, serology, cerebrospinal fluid, IgG antibodies, IgM antibodies, PCR, and lymphoproliferative techniques. Study quality was assessed using the criteria proposed by Moore and Wolfson and by the classification criteria used by the Canadian Task Force on the Periodic Health Examination. Studies were categorized both by experimental technique and by quality (high [A], intermediate [B], and low [C]) as determined by the Moore and Wolfson criteria. Overall, 25 (41%) of 61 studies, 15 (60%) of which were classified as A quality, reached a statistically significant result. According to the Canadian Task Force classification, all studies were categorized as evidence of quality II-1. Limitations of the available experimental techniques and perspectives for future research are discussed. The current review supports the need for further, objective, evidence-based examination of the relationship between HHV-6 infection and multiple sclerosis.

The role of iron and chelators on infections in iron overload and non iron loaded conditions: prospects for the design of new antimicrobial therapies.

Iron overload is known to exacerbate many infectious diseases. Infectious complications are considered to be the second main cause of morbidity and mortality in iron loaded thalassemia patients. Effective chelation therapy leading to the normalization of the iron stores could reduce the incidence of related infections. Microbial pathogens could obtain growth-essential iron from healthy hosts. Conversely, iron withholding and/or removal is an important defense strategy for mammalian hosts, which is primarily accomplished by the iron chelating proteins transferrin and lactoferrin. Chelating drugs could prevent microbial growth and play an essential role in antimicrobial therapeutic strategies. Specific mechanisms and interactions apply in the transfer or withholding of iron between the chelating drugs deferoxamine (DFO), deferiprone (L1) and deferasirox (DFRA) with microbial pathogens such as bacteria, fungi and protozoa. In some cases, chelators and in particular DFO, could act as a siderophore for the microbe and exacerbate infections such as yersiniasis and mucormycosis. Deferiprone appears to have the highest therapeutic index for long-term antimicrobial activity and the highest tissue penetration, including access to the brain. Selection of specific chelation therapy protocols could be considered in conditions where other antimicrobial therapies have failed or where resistance has developed to existing therapies.

Pharmacokinetics of cefepime in bile and gall bladder tissue after prophylactic administration in patients with extrahepatic biliary diseases.

The purpose of this study was to determine the cefepime concentrations in serum, bile and gall bladder tissue after administration of a single dose in patients with extrahepatic biliary diseases for pre-operative antimicrobial prophylaxis. During a 3-year period (1999-2002), 30 patients aged above 18 years with extrahepatic biliary diseases (acute and chronic cholecystitis and symptomatic cholelithiasis) were included in the study. Cefepime concentrations were determined by the agar microbiological diffusion method. A significant correlation between serum and gall bladder tissue concentrations of cefepime with the sampling interval was observed (r2 = 0.771, P<0.0001), whereas no correlation between serum and bile fluid concentrations of the drug was noted. In patients with non-functioning gall bladder, very low tissue levels of cefepime were detected. During the time of surgery, serum and gall bladder tissue concentrations of cefepime exceeded the minimum inhibitory concentration for 90% of the organisms (MIC90) for most common pathogens. Cefepime has the required pharmacokinetic properties to be considered for pre-operative antimicrobial prophylaxis in patients undergoing biliary tract surgery.