Serotype distribution and antimicrobial resistance of adult Streptococcus pneumoniae clinical isolates over the period 2001-2008 in Crete, Greece.

BACKGROUND: We report on the serotype distribution and the antimicrobial susceptibility patterns (ASP) to 19 antibiotics of 195 Streptococcus pneumoniae isolates (41 invasive) collected over the period 2001-2008 from adult patients. MATERIAL AND METHODS: Pneumococcal isolates were serotyped by the Quellung reaction, and ASP testing was performed using E-test. RESULTS: Isolates with intermediate and high-level resistance to penicillin increased from 17 and 12.4% over the period 2001-2004 to 31.1 and 16.7% over the years 2005-2008, respectively (p = 0.03). Macrolide resistance increased from 27.6 to 38.9%, but this was not significant (p = 0.13), while resistance to trimethoprim-sulfamethoxazole did not change over time, with approximately one fourth of the isolates being resistant. Only one isolate was resistant to fluoroquinolones. Multi-resistance was observed among 42 (58.1%) penicillin non-susceptible strains. The isolates tested belonged to 20 different serotypes. Serotypes 19F and 19A were the most common among penicillin-resistant isolates. The currently licensed 23-valent pneumococcal polysaccharide vaccine covered 98.4% of all 186 typeable S. pneumoniae strains. CONCLUSION: Our study emphasizes the importance of continued serotyping and surveillance of antimicrobial susceptibility of all S. pneumoniae clinical isolates, especially invasive ones, in order to guide the clinician in the choice of appropriate empirical antibiotic therapy for serious pneumococcal infections.

Changes in tuberculin sensitivity among first-grade students of elementary schools in Evros, Greece due to immigration.

OBJECTIVE: To investigate the tuberculin sensitivity trends among first-grade students of elementary schools tested according to the Greek national school-based screening and vaccination programme. STUDY DESIGN: Retrospective analysis of tuberculin skin test (TST) results from 1988 to 2004 in unvaccinated first-grade students in Evros, Greece. METHODS: All 6-7-year-old children who were unvaccinated for tuberculosis were tested by a highly experienced team. This study tested whether gender (male vs female), national origin (native vs foreign-born children) and place of residence (urban vs semi-urban vs rural) correlated with tuberculin reaction positivity. RESULTS: In total, 8588 children (47.1% girls) were tested. Tuberculin reaction positivity was independent of gender. The difference in TST positivity between native and foreign-born children between 1993 and 2004 was highly significant, with substantially more foreign-born children having a positive Mantoux test (P<0.0001). The percentage of children with a positive TST peaked at 13% in 1995 due to initial admission of foreign-born children, originating from countries of the former Soviet Union, into the Greek educational system. In addition, a positive Mantoux test was more common among children living in rural (8.1%) and semi-urban (6.4%) areas compared with children living in urban areas (3.5%, P<0.0001). CONCLUSION: The increase in TST positivity noted was due to admission of foreign-born children into the Greek educational system. School-based tuberculosis screening programmes should continue in Greece because the prevalence of tuberculosis appears to show substantial variation between years.

Antimicrobial susceptibilities of 930 Haemophilus influenzae clinical strains isolated from the island of Crete, Greece.

BACKGROUND: Haemophilus influenzae is an important human pathogen. MATERIALS AND METHODS: The purpose of the present retrospective study is to describe the antibiotic susceptibility to several common antibiotics of 930 consecutive clinical isolates of H. influenzae over the period of 1996-2005 in a tertiary general hospital on the island of Crete, Greece. RESULTS: Overall, 9.5% of the isolates were beta-lactamase producing. Resistance to ampicillin and amoxicillin-clavulanate was observed in 11 and 0.6% of the strains, respectively, remaining stable throughout the study period. Resistance to tetracycline increased from 1.6% in 1996 to 38% in 2005, while resistance to ciprofloxacin and ofloxacin was <1%. A significant decrease in resistance to trimethoprim-sulfamethoxazole was observed during the study period. No significant changes in resistance to other antimicrobials were seen. CONCLUSIONS: Amoxicillin-clavulanate and older quinolones remain potent agents against H. influenzae. Constant surveillance ofantibiotic susceptibility of H. influenzae clinical isolates is important in order to guide appropriate empirical antibiotic therapy.

Thrombocytosis in childhood.

Thrombocytosis is a frequent finding in hemograms obtained from hospitalized and ambulatory children due to the widespread use of automated blood cell counters. Pediatricians are commonly puzzled in cases of thrombocytosis to determine the underlying cause and the need for therapy. The purpose of this review is to assist the general pediatrician into dealing with this common hematological finding in every day clinical practice. Fortunately, primary thrombocytosis or essential thrombocythemia, a clonal disease, is exceedingly rare in childhood, but may be associated with thromboembolic and hemorrhagic complications. On the other hand, secondary or reactive thrombocytosis is very common and is due to a variety of conditions, such as acute and chronic infections, iron deficiency, bleeding, hemolytic anemias, collagen vascular diseases, malignancies, drugs and splenectomy. Treatment of reactive thrombocytosis should be directed to the underlying problem alone. Administration of platelet aggregation inhibitors such as aspirin is unwarranted. Consultation is necessary only for the rare child with extreme thrombocytosis who has clinical and/or laboratory criteria consistent with essential thrombocythemia, or in whom a hemorrhagic or thrombotic complication has developed.

Antimicrobial resistance of Mycobacterium tuberculosis isolates from children in Greece, 1994-2004.

OBJECTIVE: To document the prevalence of resistance to various agents of Mycobacterium tuberculosis strains derived from children over 1994-2004. DESIGN: We prospectively studied the susceptibility patterns of 77 strains of M. tuberculosis isolated from the same number of children, which provided 112 positive samples. RESULTS: Most children were boys (53.2%), native Greeks (87%) and aged under 2 years (41.5%). Sample origin was mainly gastric fluid (97 cases, 86.6%). Sixty-one isolates (79.2%) were susceptible to all anti-tuberculosis agents and 16 (20.8%) were resistant to > or =1 drug. Multidrug resistance (MDR), resistance to at least isoniazid (INH) and rifampicin (RMP), was seen in three cases (3.9%). On comparing resistance to INH, RMP and streptomycin (SM) and MDR in children and adults diagnosed with tuberculosis in our centre during the same time period, SM resistance was significantly more common in children (P < 0.001), while a trend for increased resistance to INH was also observed in children (P = 0.079). CONCLUSION: Resistance of M. tuberculosis isolates to the first line anti-tuberculosis drugs appears to be comparable in children and adults in Greece, while SM resistance appears to be more common in children. Tracing the sources of these children is important for the effective surveillance and treatment of tuberculosis.

Association between bone scintigraphy and serum levels of tumor markers in the detection of bone disease in breast cancer patients.

PURPOSE: To evaluate the diagnostic value of bone scan in association with measurements of serum CEA, CA 15-3 and TPA levels in breast cancer (BC) patients. PATIENTS AND METHODS: From September 1999 to January 2005, 89 women with BC who had undergone bone scintigraphy as part of their follow-up were retrospectively evaluated. Serum tumor markers levels were compared with the results of bone scintigraphy. Patients with positive bone scans were divided into 3 groups: group 1: 1-3, group 2: 4-5, group 3: >5 bone lesions. Serum CEA, CA 15-3 and TPA levels of 7 ng/ml, 35 U/ml and 90 U/I, respectively, were adopted as the upper limit of normal. RESULTS: Serum CA 15-3 was significantly higher in patients with a positive bone scan (p=0.017). For CEA and TPA, no significant difference was found between patients with and without bone metastases. Twenty-five of 70 patients (36%) with normal CEA had bone metastases. Four of 50 (8%) patients with normal CA 15-3 and 15 of 51 (29%) patients with normal TPA had a positive bone scan. The combination of CA 15-3 with TPA showed 100% sensitivity in detecting bone metastases in all patient subgroups. In all 42 patients without bone metastases, CA 15-3 and/or TPA levels were normal. CONCLUSION: CA 15-3 but not CEA or TPA is sensitive and specific for the correct determination of bone scintigraphy. CA 15-3 plus TPA represent the best combination in association with bone scanning. However, due to frequent false negative results of all tumor markers, it is not recommended to reject a bone scan on the basis of tumor markers levels.

Resistance of Mycobacterium tuberculosis isolates in different populations in Greece during 1993-2002.

OBJECTIVE: To document the prevalence of resistance of Mycobacterium tuberculosis to isoniazid (INH), rifampicin (RMP) and both combined (multidrug resistance [MDR]) in Greece from 1993 to 2002. DESIGN: We studied a single sputum sample per patient from 4108 patients referred to the Greek National Referral Centre for Mycobacteria. Patients were divided into native Greeks, immigrants and repatriated Greeks originating from the former Soviet Union. Prior treatment status was not recorded. RESULTS: A statistically significant increase in resistance to INH and RMP and MDR was noted comparing the years 1993-1997 to 1998-2002 (P < 0.0001). Resistance to INH and RMP and MDR rose from 5.6% to 7.71%, from 1.57% to 4.49% and from 1.23% to 3.98%, respectively, among native Greeks and from 23.63% to 32.91%, from 6.36% to 15.19% and from 6.36% to 13.92% among repatriated Greeks. Smaller changes were seen among immigrants (from 15.43% to 9.57% for INH, from 5.51% to 6.12% for RMP and from 5.71% to 5.32% for MDR). CONCLUSION: We documented an increase in M. tuberculosis resistance to INH and RMP, and MDR. This was mainly limited to native and repatriated Greeks. Although this is likely the result of immigration and of mismanagement of index cases in Greece, molecular methods are needed to better describe the situation.

Fractionated cyclophosphamide and etoposide for children with advanced or refractory solid tumors: a phase II window study.

PURPOSE: Cyclophosphamide (CPA) has a broad spectrum of activity against solid tumors. Hepatic self-induction of the active metabolite 4-hydroxycyclophosphamide occurs after repeated administration. We evaluated the clinical efficacy of a window regimen that administers fractionated CPA in conjunction with etoposide (VP16) in children with advanced or refractory solid tumors. PATIENTS AND METHODS: Seventeen children with advanced (n = 12) or refractory (n = 5) solid tumors were entered onto this phase II window study. The treatment regimen consisted of intravenous (IV) CPA 500 mg/m(2)/d and IV VP16 100 mg/m(2)/d. Both drugs were administered daily by short infusions for 5 consecutive days. RESULTS: A total of 34 courses were administered, with a median of two courses per patient. The median interval between chemotherapy courses was 21 days (range, 17 to 35 days). Thirty-three courses were assessable for toxicity, and all patients were assessable for response. No life-threatening toxicities were observed. The incidence of grade 3 or 4 neutropenia was 94% and of fever and neutropenia 38%. Fever and neutropenia occurred after 12 of 26 courses without recombinant human granulocyte colony-stimulating factor (rhG-CSF) and after one of eight courses with rhG-CSF (P =. 09). Grade 3 or 4 thrombocytopenia occurred after 10 courses (29%). There were no positive blood cultures. One heavily pretreated patient developed a localized perirectal abscess that required drainage. There were 10 patients (59%) with partial responses, four (23.5%) with stable disease, and three with progressive disease. CONCLUSION: Fractionated IV CPA and VP16 over 5 days can be safely administered in children with advanced or refractory solid tumors and has notable antineoplastic activity.

Systemic mycoses in the immunocompromised host: an update in antifungal therapy.

Despite significant advances in the management of immunosuppressed patients, invasive fungal infections remain an important life-threatening complication. In the last decade several new antifungal agents, including compounds in pre-existing classes (new generation of triazoles, polyenes in lipid formulations) and novel classes of antifungals with a unique mechanism of action (echinocandins), have been introduced in clinical practice. Ongoing and future studies will determine their exact role in the management of different mycoses. The acceleration of antifungal drug discovery offers promise for the management of these difficult to treat opportunistic infections.

Orofacial viral infections in the immunocompromised host.

Orofacial viral infections are common in immunocompromised patients. Herpes simplex virus (HSV) infections are the most common. Varicella-Zoster virus (VZV) infections are less common, but usually more severe. Epstein-Barr virus (EBV) may produce ulcers, lymphoproliferative syndromes or oral hairy leukoplakia (HL). Human herpes virus 6 (HHV 6) may be the etiology of recurrent aphthous stomatitis, while human herpes virus 7 (HHV 7) has an unclear role. Human herpes virus 8 (HHV 8) is the etiologic agent of Kaposi sarcoma. Human papilloma viruses (HPVs) cause warts, papillomas and epithelial hyperplasia. Molluscum contagiosum is caused by a poxvirus. All herpes viruses (HSV, VZV, CMV, EBV, HHV 6, HHV 7, HHV 8) and many HPVs are associated with neoplasias. Research is ongoing to clarify the role of other viruses in the development of infections and lesions in the orofacial area.

Merkel cell carcinoma: a case series of twelve patients and review of the literature.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare tumor of the skin. MATERIALS AND METHODS: A retrospective analysis of 12 cases of MCC diagnosed and treated over a 14-year period. RESULTS: Seven females and 5 males, with a median age of 72 years and MCC of the face (5), trunk (1) and extremities (6), were studied. The stage was I in 2 cases and II in 10. Eight patients had surgery, two surgery and chemotherapy and two chemotherapy only. The last two patients died of disease after 10 and 16 months. Three patients suffered locoregional recurrence after 4, 6 and 24 months and three were lost to follow-up after 8, 9 and 24 months while disease-free. Two disease-free patients died of unrelated causes after 4 and 48 months, while three were alive and well after 24, 48 and 84 months. The three relapsing patients received chemotherapy in addition to local radiation in one case. One is alive and well, the other alive with disease and the third died of disease after 84, 107 and 10 months, respectively. CONCLUSION: MCC often recurs locally. Surgery is the treatment of choice, while radiotherapy is important for local control. Chemotherapy produces responses in the neoadjuvant setting or after relapse.

[A psychological study, using interviews and projective tests, of patients seeking anonymous donor artificial insemination]. / Etude, par entretiens et tests projectifs, du psychisme de patient(e)s ayant recours à l'insémination artificielle par donneur anonyme.

A Thematic Aperception Test was used with 13 male and 16 female patients who were requesting A.I.D. The following main psychological reactions were found in women: anxiety and depression (fear of rejection by their family and friends; lowering the image of the husband--the donor being considered as a rival), aggression (the narcissistic woman "demands" A.I.D.; the donor is esteemed highly); mother is protective ("true" paternity comes through love of the child and the need to forget the donor). They found, in men: an inability to abandon fertility as lost (with denial of sterility); ambivalence, castration anxiety and a feeling of being excluded from the mother-child symbiosis with later acceptance of loss of fertility and (sometimes excessively) identification with the "mother". Most subjects studied were not intending telling the child about his true origin; because disclosure would be tantamount to transgressing twice over the laws of paternity and the rules against Oedipus behaviour. There is often a great difference between the ways the partners view the matter and inter-relate. We strongly recommend that psychological advice should be taken before treatment with A.I.D. is started.

Erythema nodosum associated with Salmonella enteritidis.

BACKGROUND: Erythema nodosum (EN) is the most frequent type of panniculitis in childhood. Although frequently idiopathic, it may be associated with a wide variety of conditions ranging from infections, to sarcoidosis, to collagen vascular diseases to drugs. CASE REPORT: We present an 8-year-old boy who developed EN during the course of febrile gastroenteritis due to salmonella enteritidis. He received intravenous ampicillin 150 mg/kg/day divided in equal doses every six hours for 10 days. The skin lesions gradually disappeared, and he recovered fully without sequelae. CONCLUSIONS: Salmonellosis should be considered in the differential diagnosis of EN in children with gastrointestinal symptoms, and stool cultures should be performed when indicated.

Attenuation of cytogenetic effects by erythropoietin in human lymphocytes in vitro and P388 ascites tumor cells in vivo treated with irinotecan (CPT-11).

Erythropoietin (EPO) is a protein widely used against drug induced anemia at cancer patients. Irinotecan (CPT-11) is a genotoxic topoisomerase I inhibitor. We investigated the genotoxic, cytostatic and cytotoxic effects of EPO in the presence and in the absence of CPT-11 in human lymphocytes in vitro and in ascites cells of P388 leukemia in vivo. The levels of genotoxicity, cytostaticity and cytotoxicity were evaluated in human lymphocytes in vitro, and in P388 ascites tumor cells in vivo. The results show that EPO is not genotoxic. Unlikely to EPO, CPT-11 caused severe genotoxic, cytostatic and cytotoxic effects by significantly increasing SCE levels and decreasing PRI and MI values in peripheral lymphocytes in vitro and in P388 ascites tumor cells in vivo. Adding EPO in human lymphocyte cultures in vitro and in P388 leukemia bearing mice in vivo in the presence of CPT-11 decreased SCEs levels and increased PRIs and MIs were observed compared with cells treated either in vitro or in vivo with CPT-11 alone, which shows that EPO protected cells from the toxic action of CPT-11. EPO's protective action on human peripheral lymphocytes in vitro and P388 cells in vivo from the topoisomerase I inhibitor CPT-11, lead us to propose it as a geno- and cytoprotective agent.

Clinical presentation of zygomycosis.

Zygomycetes are filamentous fungi with a worldwide distribution. This class of fungi encompasses two orders, i.e. the Mucorales and the Entomophthorales. Members of the latter are associated with chronic cutaneous and subcutaneous infections that are limited to the tropics and rarely disseminate to internal organs. The order Mucorales includes several species involved in rhinocerebral, pulmonary, cutaneous, gastrointestinal and other less frequent infections in immunocompetent and immunocompromised individuals, and is characterized by a tendency to disseminate. Portals of entry of zygomycetes are usually the lungs, skin, and gastrointestinal tract. A characteristic property of zygomycetes is their tendency to invade blood vessels and to cause thrombosis-processes that result in subsequent necrosis of involved tissues. Risk factors associated with zygomycosis include prolonged neutropenia and use of corticosteroids, solid organ or haematopoietic stem cell transplantation, AIDS, poorly controlled diabetes mellitus, iron chelation with deferoxamine, burns, wounds, malnutrition, extremes of age, and intravenous drug abuse. Recently, the widespread use of voriconazole for prophylaxis or treatment of aspergillosis in patients with haematological malignancies has been linked with a rise in the numbers of cases of invasive zygomycosis. As the symptoms, clinical signs and imaging findings of these infections are non-specific, a high index of suspicion is required for timely diagnosis. Early diagnosis, correction of the underlying predisposing factors, aggressive surgical debridement of all infected tissues and lengthy administration of antifungals are the only potentially curative options for this rare but emerging invasive fungal infection.