Hypogammaglobulinemia and Poor Performance Status are Predisposing Factors for Vancomycin-Resistant Enterococcus Colonization in Patients with Hematological Malignancies.

OBJECTIVE: Vancomycin-resistant enterococci (VRE) are common pathogens of hospital-acquired infection. Long hospitalization periods, use of broad-spectrum antibiotics, and immunosuppression are major risks for VRE colonization. We aimed to evaluate patients' characteristics and factors that may contribute to VRE colonization. MATERIALS AND METHODS: Data of 66 patients with colonization and 112 patients without colonization who were hospitalized in the hematology clinic were collected. Hematological malignancies, preexisting gastrointestinal complaints, the presence of hypogammaglobulinemia at the time of diagnosis, complications like neutropenic enterocolitis (NEC), and Eastern Cooperative Oncology Group (ECOG) and Karnofsky performance statuses were recorded. RESULTS: Ages of the patients ranged between 19 and 95 years (mean: 55.99). Karnofsky and ECOG scores were statistically related to VRE colonization (p<0.000 and p<0.000), though only the Karnofsky score was significant based on logistic regression analysis. Almost all patients with acute leukemia (45 patients) had been on antibiotics (piperacillin-tazobactam, ceftazidime, and meropenem), while no patients with myelodysplastic syndrome, myeloma, or benign diseases and 2 patients with lymphoma and 1 with chronic myeloid leukemia were on antibiotics. Median time for colonization regardless of antibiotic use and diagnosis was 4.5 days (range: 3-11 days). In the VRE-colonized group, 40.9% of patients had NEC development, while in the non-colonized group, only 1.7% had NEC development. In the VRE-colonized group 46 patients (69.7%) and in the non-colonized group 27 patients (24.1%) had hypogammaglobulinemia at diagnosis; among these patients, 23 patients in the VRE-colonized group (50%) had a B-cell malignancy (lymphoma, myeloma, or chronic lymphocytic leukemia). CONCLUSION: Besides already anticipated diseases like leukemia, B-cell malignancies are also at high risk for colonization. This proclivity may be attributed to lack of gastrointestinal IgA due to hypogammaglobulinemia. Prolonged hospitalization (>7 days) may also be accepted as a risk factor, independent of diagnosis or antibiotic use. Performance status is also an important factor for colonization, which may be related to poorer hygiene and increased external help.

[Microbiological approach to a possible infective endocarditis case caused by Aggregatibacter actinomycetemcomitans]. / Aggregatibacter actinomycetemcomitans kaynakli olasi enfektif endokardit olgusuna yaklasim.

Aggregatibacter (Actinobacillus) actinomycetemcomitans, a small, gram-negative coccobacillus that grows slow and fastidious, is generally colonized in the oral cavity. It is a rarely seen bacterium because of the difficulty of isolation but it can be a causative agent for dental infections and infective endocarditis (IE) particularly in the persons having prosthetic heart valves. In this report, a possible IE case caused by A.actinomycetemcomitans in a patient with aortic valve replacement has been presented. A 36-year-old man has admitted to Trakya University Hospital, Health Center for Medical Research and Practice, with the complaints of chills, malaise, intermittent fever, severe arthralgia and weight loss (20 kg). During his follow-up period, the blood cultures that were obtained three week intervals yielded the identical gram-negative coccobacilli morphology. The patient was then diagnosed as possible IE on the basis of having one major (growth of the typical microorganisms that may cause IE in two different blood cultures) and two minor (presence of prosthetic valve and high fever) criterias. The isolate could not be identified with conventional methods, while it was identified as Francisella tularensis with VITEK 2 (bioMerieux, France) system. Hence this identification was not confirmed by real-time Taqman polymerase chain reaction, so MALDI-TOF mass spectrometry was used to identify this bacteria. In the first run of the study, the isolate was named as Shigella dysenteriae initially, however when it was retested the next day it was identified as A.actinomycetemcomitans. In order to enlighten these conflicting results, 16S and 23S ribosomal DNA sequence analysis was performed, and consequently the bacterium was identified as A.actinomycetemcomitans. Doxycycline (2 x 100 mg po, 20 days) and streptomycin (2 x 10 mg/kg im, 10 days) therapy were initiated, considering the initial suspicious identification (F.tularensis), and on the fifth day of therapy the blood culture was negative with the regression of patient's complaints. Therapy continued with the addition of rifampicin to doxycycline from the 21(st) day and the patient discharged with cure. As a result, the identification of an exceptional bacterium like A.actinomycetemcomitans may be difficult and time-consuming in certain laboratory facilities. So, the use of different identification methods in addition to classical methods are needed to overcome such a problem, especially for uncommon isolates and clinically discordant cases. This case was presented because A.actinomycetemcomitans is a rare etiological agent for IE patients and it could be a good example to draw attention to the problem when identifying the organism using automatized identification systems.

Mediterranean spotted fever in the Trakya region of Turkey.

Mediterranean spotted fever (MSF) is caused by a tick-borne pathogen, Rickettsia conorii subsp. conorii, belonging to the spotted fever group (SFG) rickettsiae. The aim of the present study was to evaluate the cases with confirmed diagnosis of MSF from 2003 to 2009 in the Trakya region of Turkey. Patients with high fever, maculopapular rash (involving the palms or soles) and/or a black inoculation eschar at the site of the tick bite (tache noire) were included in the study. Before doxycycline treatment, skin biopsy specimens, preferably from the eschar or from the maculopapular rash, were obtained for DNA extraction. Immunofluorescence assay (IFA) was performed to detect IgM and IgG antibodies against R. conorii in acute and convalescent sera. Afterwards, a standard PCR reaction using primers suitable for hybridisation within the conserved region of genes coding for outer membrane protein A (ompA) and citrate synthase (gltA) and DNA sequencing were performed. There were 128 patients with confirmed MSF diagnosis. Using IFA, seroconversion or a fourfold or greater rise in titre was observed in 97 (77%) patients, whereas a single high titre was demonstrated in 16 (12.7%) patients. According to PCR analysis, 77 (72.6%) of 106 biopsy samples showed positive results. Of these, 58 (73%) of 79 biopsy specimens were from the eschar and 19 (70%) of 27 specimens were from the maculopapular rash. No significant difference was found between the rate of positive skin biopsies taken from the eschar and the maculopapular rash. DNA sequence analysis was performed to all PCR-positive cases, and R. conorii conorii (type strain: Malish, ATCC VR-613) was detected in each of them. MSF is prevalent, but has been underdiagnosed and underreported so far in Turkey. It is a potentially severe and even fatal disease resembling viral haemorrhagic fevers that has to be included in the differential diagnosis of febrile illness associated with thrombocytopenia, even in the absence of an eschar or a tick bite. While IFA allows for retrospective diagnosis in MSF, advanced molecular techniques provide the rapid detection of rickettsia in all skin samples, including eschar and maculopapular rash.

Negative serology: could exclude the diagnosis of brucellosis?

Two cases of brucellar spondylodiscitis of the lumbar area were presented. Although both cases showed typical radiological changes, serological tests could not detect Brucella agglutinating antibodies. One of the patients was bacteremic and Brucella spp. was identified from blood culture. In the second patient needle biopsy was required for definite diagnosis. Although small, serologic tests have a certain rate of false negative results in brucellosis. Thus, a negative serology should not exclude the diagnosis of brucellosis, as it is demonstrated in the current cases.

[Evaluation of epidemiological characteristics and risk factors of candidemia in adult patients in a tertiary-care hospital]. / Bir üçüncü basamak hastanesinde eriskin kandidemi olgularinin epidemiyolojik özellikleri ve risk faktörlerinin degerlendirilmesi.

Candida species which are currently the fourth most common cause of nosocomial bloodstream infections, are associated with a significant morbidity and mortality. The aim of this retrospective case-control study which included adult patients was to determine the epidemiology of candidemia and to evaluate risk factors for the development of candidemia and mortality at a tertiary-care education hospital over a 1-year period. A total of 38 candidemia cases (23 were male; age range: 17-82 yrs; mean age: 61.4 ± 13.5 years) were identified among 22.507 patients hospitalized during the study period (January 1-December 31, 2008) and the overall incidence was found as 16.8 per 10.000 hospital admissions. Control group (n= 36; 22 were male; mean age: 60.9 ± 16.3 years) was selected among patients who had no signs and symptoms of candidemia and had negative blood cultures during the study period. Thirty-six (95%) patients with candidemia were identified as nosocomial infection. The most frequently isolated species were C.albicans (55.2%) and C.parapsilosis (28.9%) and the primarily identified origin of infection was central venous catheter use (39%). Candida spp. Isolation was most frequent in patients hospitalized in intensive care units (13/38; 34.2%), followed by surgery (n= 8; 21%) and chest diseases (n= 5; 13). Univariate analysis revealed that presence of a central venous catheter [odds ratio (OR): 4.33; 95% confidence interval (CI): 1.63-11.47, p= 0.003] and the length of hospitalization (OR: 0.97; CI: 0.94-1.00, p= 0.01) were the most frequently associated factors with an increased risk of candidemia compared to controls. However, multivariate analysis exhibited presence of a central venous catheter (OR: 2.90; CI: 1.04 8.11, p= 0.04) as the only independent risk factor for the development of candidemia. Therapy was initiated with intravenous fluconazole (mean duration of therapy 13.2 ± 6.25 days) and in three patients following fluconazol use step-up therapy was initiated. Total mortality rate was 58% (22/38) in our case series. Risk factors for mortality due to candidemia in the univariate analysis were detected as no response to antifungal treatment (OR: 0.23; CI: 0.11-0.51, p< 0.001), underlying disease other than trauma (OR: 0.06; CI: 0.003-1.24, p= 0.02), and high Charlson index (OR: 0.60; CI: 0.38-0.93, p= 0.03), however those factors were not found significant by multivariate analysis. There was also a statistically significant correlation between Charlson index and treatment response (mean Charlson index was 3.5 ± 1.9 in therapy-responded patients and 4.8 ± 1.8 in non-responders; p= 0.03). Since the risk of developing candidemia was significantly higher in severely diseased patients using central venous catheter or with prolonged hospitalization, response to antifungal therapy may be insufficient, leading to higher mortality.

CTX-M type extended spectrum beta-lactamases in Escherichia coli isolates from community acquired upper urinary tract infections at a university in the European part of Turkey.

Extended spectrum beta-lactamase (ESBL) producing Escherichia coli has been an emerging etiologic agent in the community acquired infections. We investigated the occurrence of ESBL producing E. coli isolated from patients admitted with community acquired urinary tract infection (UTI) to the hospital of the Trakya University, Turkey during 2006. Eleven single patient isolates of E. coli harboring ESBL were identified among 30 E. coli isolated from patients admitted with symptoms corresponding to upper UTI. CTX-M type ESBLs were detected in all 11 ESBL-producers by isoelectric focusing and polymerase chain reaction screening. Sequence analysis revealed CTX-M-1 in one isolate, CTX-M-3 in three isolates and CTX-M-15 in seven isolates. ESBL-producing E. coli isolated from community acquired UTIs are widespread in the European part of Turkey.

[Staphylococcus aureus hepatic abscess associated with cervical lymphadenitis]. / Servikal lenfadenit esliginde gelisen Staphylococcus aureus'un etken oldugu karaciger apsesi.

Pyogenic liver abscesses usually develop secondary to biliary tract and intraabdominal infections and members of the Enterobacteriaceae family are usually implicated as the etiologic agents. In this report a case of hepatic abscess devoloped secondary to cervical lymphadenitis caused by Staphylococcus aureus, was presented. Twenty-one years old male patient was admitted to the hospital with complaints of fever, swelling and pain at the right side of the neck and difficulty in swallowing. Physical examination revealed painful submandibular lymphadenopathy with hyperemia. Upon demonstration of cystic lymphadenopathy by magnetic resonance imaging of the neck, the mass was aspirated. Gram-positive cocci with abundant leucocytes were detected in Gram stained smears of the aspiration material and methicillin-susceptible S. aureus (MSSA) was identified in the culture. Treatment with ampicillin/sulbactam (4 x 1.5 g/day) was initiated. However, since patient still had fever and abdominal pain, nausea and vomitting were also added to his complaints, abdominal ultrasonography and computerized tomography (CT) were done and abscesses were demonstrated in liver. The abscesses were drained under CT guidance and the fever of the patient resolved. Treatment with ampicillin/sulbactam was continued for 6 weeks. Although it was considered that the hematogenous spread of MSSA that led to cervical lymphadenitis caused the hepatic abscesses, the agent was neither isolated from the blood culture nor from the hepatic abscess material. It should always be taken into consideration that liver abscesses might accompany distant infections and antibiotic therapy alone might not be sufficient for the complete resolution of such infections.

[Etiologic agents and risk factors in nosocomial urinary tract infections]. / Nozokomiyal üriner sistem enfeksiyonlarinda etiyolojik etkenler ve risk faktörleri.

Nosocomial urinary tract infection (NUSI) is one of the most common hospital acquired infections. In this study, we aimed to determine the risk factors, frequency and the bacterial etiology of NUSI in hospitalized patients at Trace University Hospital, Turkey. Between September 1st 2004 to March 1st 2005, 104 NUSI episodes from 91 adult patients (mean age; 60.8 +/- 16.1 years; 46 were female) were determined among 8704 patients admitted to the hospital. During the study period, cumulative incidence of NUSI was 1.04% and episode rate of NUSI was 1.19%. The most important risk factors for NUSI were detected as urinary catheterization (78.8%), antimicrobial therapy within the previous 15 days (60.6%), fecal incontinence (33.7%) and surgical operations [29.8% (42% of them were urological pertainings)]. In 37.8% of the episodes urinary catheterization was considered as performed unnecessarily. In 26% of the episodes another infection (pneumoniae, abdominal infection, wound infection) accompanied. The causative microorganisms were resistant to the antibiotics used for therapy in 93.6% of the episodes. A total of 118 microorganisms (14 were polymicrobial) have been isolated from the urine cultures. The most frequently isolated ones were Escherichia coil (n: 48; 40.8%), Candida spp. (n: 27; 23%), Enterococcus spp. (n: 13; 11%), Pseudomonas aeruginosa (n: 9; 7.6%), Klebsiella pneumoniae (n: 8; 6.8%) and Acinetobacter spp. (n: 5; 4.2%). The highest susceptibility rates of E. coli isolates were against imipenem and nitrofurantoin (100%) and amikacin (97.7%), the lowest susceptibility rates were against ampicillin (26.7%) and amoxycillin-clavulonate (44.4%). No glycopeptid resistance was detected for Enterococcus spp. while the susceptibility rates to penicilin and nitrofurantoin were 38.5% and 63.6%, respectively. Since the number of the other bacterial species was low (<10) their antimicrobial resistance rates were not evaluated. Extended-spectrum beta-lactamase (ESBL) production was determined in 27% of E. coli and in 25% of K. pneumoniae isolates, and cases with ESBL producing strains had significiantly higher antibiotic consumption rate in the previous 15 days (p = 0.004). Blood cultures which were collected during NUSI episodes yielded positive results in 31.8%. The mortality rate due to NUSI was significantly higher in cases with bloodstream infection (p = 0.000). In conclusion, the high rates of NUSI associated with bloodstream infections and mortality detected have pointed out serious problems in our hospital, and indicated that more attention should be paid on urinary catheterisation, rational antibiotic usage and control of nosocomial infections.

[Retrospective evaluation of the cases prediagnosed as viral encephalitis in Trace University Hospital between the period of 2000-2005]. / Trakya üniversitesi tip fakültesi hastanesinde 2000-2005 yillari arasinda viral ensefalit ön tanili olgularin retrospektif degerlendirilmesi.

In this study, a total of 17 adult patients ((> or =18 years old; 12 male, 5 female) with encephalitis followed up in neurology and infectious diseases clinics of Trace University Hospital between the years 2000-2005 were retrospectively analyzed. The most common signs and symptoms were confusion (n: 13; 76.4%), nausea and vomiting (n: 13; 76.4%), disorientation (n: 12; 70%), fever and headache (n: 11; 64.7%), amnesia (n: 10; 58.8%), convulsions (n: 9; 52.9%), agitation (n: 7; 41%), dysphasia and aphasia (n: 6; 35.2%), nuchal stiffness (n: 5; 29.4) and focal neurological signs (n: 1; 5.8%). Six of the patients were admitted to the hospital during summer, six during winter, four during spring and one during autumn. Eleven (64.7%) of the patients had electroencephalographic signs compatible with encephalitis. Encephalitis related signs were detected in 83.3% (10/12) of the patients by cranial magnetic resonance imaging and in 58.3% (7/12) by computerized tomography. Cerebrospinal fluid (CSF) examination revealed low glucose levels in 17.6% (3/17), high protein levels in 47% (8/17) and increased white blood cells with a predominance of lymphocytes in 41.2% (7/17) of the cases. CSF findings were within normal limits in 23.5% (4/17) of the patients. Empirical acyclovir treatment was given to all patients. One patient died at the acute phase of the infection while all the other 16 recovered. Since none of the CSF samples yielded bacterial growth, all of the patients were diagnosed as viral encephalitis. However, no investigation was performed to identify the viral etiology and this was the major limitation owing to the inadequacy of laboratory facilities during the study period and/or unawareness of the physicians about viral identification methods.

[Short communication: Evaluation of the flu vaccine administered to health care workers in Trakya University Hospital in 2006]. / Kisa bildiri: Trakya Universitesi Hastanesi saglik Calisanlarina 2006 yilinda uygulanan grip asisinin degerlendirilmesi.

After the detection of human cases of highly pathogenic avian influenza A (H5N1) virus in Eastern Turkey in January 2006, Turkish Ministry of Health has had declared "National Plans of Activity for Pandemic Influenza". All health-care facilities were recommended to develop contingency plans. Then the essential activities were started in August 2006 in Trakya University, Faculty of Medicine (Edirne, Trace region of Turkey), and institutional education about pandemic influenza and preventive measures was implemented to health care workers (HCWs). In November 2006, health care workers were offered inactivated flu vaccine (Vaxigrip, Sanofi Pasteur, France) supplied by the Ministry of Health. The aim of this questionary survey was to evaluate the visions and conceptions of health care workers about influenza vaccination during the vaccination campaign. All the participants were informed by using an information form including the indications, contraindications and possible adverse reactions of flu vaccine, and were requested to complete the questionnaire about influenza vaccination according to their own perception before vaccination. Vaccine recipients were also invited to the vaccination unit if they had any adverse reaction. A total of 1041 HCWs (560 female, 481 male; mean age: 32.8 +/- 8.2 years) completed the questionnaire. Of them 884 subjects (85%) have accepted to be vaccinated, while 157 subjects (15%) have not. It was determined that 72 HCWs (6.9%) had been administered flu vaccine in 2005, and 38 (3.7%) have had an underlying chronic disease requiring medical therapy. Six subjects (16%) with an underlying chronic disease were vaccinated in 2005, while 66 HCWs (6.6%) without any chronic disease received vaccination voluntarily. Seven workers (0.7%) declined vaccination as they defined hypersensitivity to egg, and 84 workers (8%) had influenza vaccine voluntarily before the campaign in 2006. Sixty six workers (6.3%) have refused to be vaccinated as they considered influenza vaccination ineffective to protect against flu. Two workers (0.2%) had allergic skin reactions such as erythema and itching after vaccination. It can be concluded that influenza vaccination of the health care workers is a part of infection control policies and it is also a matter of patient safety. The implementation of necessary education programmes and attempts to emphasize the importance of vaccination of health care workers especially dealing with high risk patients, would be of crucial importance to decrease the morbidity and mortality due to influenza infections.

[Mediterranean spotted fever due to contact with dog-tick]. / Köpek kenesi ile temas sonrasinda gelisen akdeniz benekli atesi.

Mediterranean spotted fever (MSF) is one of the tick-borne rickettsial infections caused by Rickettsia conorii. It is transmitted to humans by brown dog ticks (Rhipicephalus sanguineus). In this case report, a 16-years-old male patient who was diagnosed as MSF after an exposure to dog-tick in Bartin province (located at middle Black Sea region of Turkey) has been presented. His history revealed that, five days before admission to the hospital (on June, 2007) he had cleaned dog-ticks from his dog, and after 12 hours he found a stucked tick on his leg and he took it out right away with a tweezer. High fever, headache and generalized maculopapular rash including soles and palms and a black-colored lesion at the tick bite site developed three days later. In clinical examination, there was a black escar circled with a red-purple colored halo in front of the right tibia at the site of the tick bite showing high similarity to "tache noire" which was specific to MSF. Indirect immunofluorescence assay (IFA) for Rickettsia yielded negative result in the serum sample collected on admission day, however, it was found positive at 1/512 titer in the serum sample collected 10 days after admission. The patient has recovered completely without any complication after 10 days of doxycycline therapy. The aim of this presentation is to point out that MSF should be considered for the differential diagnosis of a patient with a history of tick bite, fever, maculopapular rash, headache, myalgia, arthralgia and especially with black escar during summer months in our country where the incidence of tick-borne infections has been increasing since recent years.

Acute abdomen caused by brucellar hepatic abscess.

Brucellosis is a zoonotic infection that is transmitted from animals to humans by ingestion of infected food products, direct contact with an infected animal, or aerosol inhalation. The disease is endemic in many countries, including the Mediterranean basin, the Middle East, India, Mexico, Central and South America and, central and southwest Asia. Human brucellosis is a systemic infection with a wide clinical spectrum. Although hepatic involvement is very common during the course of chronic brucellosis, hepatic abscess is a very rare complication of Brucella infection. We present a case of hepatic abscess caused by Brucella, which resembled the clinical presentation of surgical acute abdomen.

Prospective evaluation of rickettsioses in the Trakya (European) region of Turkey and atypic presentations of Rickettsia conorii.

In 2004 between the months of May-November, 11 patients with spotted fever group (SFG) rickettsioses were admitted to the Trakya University Hospital in Edirne, Turkey. SFG rickettsioses were diagnosed clinically. Before treatment, punch biopsy from skin lesions, especially from the eschar, was performed. Serum specimens were tested by IFA using a panel of nine rickettsial antigens, including SFG rickettsiae and R. typhi. Western blotting and standard PCR were also performed. The average age of the 11 patients (4 male and 7 female) was 51 years. All the patients had high fever; 10 (91%) had maculopapular rash; 8 (73%) had rash in the palms or on the soles. Five patients had a unique eschar; two had double eschars (64%). Two patients presented with multiple organ failure and one of them died. All the patients had significant antibody titers against SFG rickettsiae. PCR experiments of skin biopsies were positive in six (60%) of 10 skin biopsy samples and DNA sequencing of the positive PCR products gave 100% homology with Rickettsia conorii Malish 7 for opmA and gltA. Trakya Region in an endemic area for rickettsioses. In this series, three patients presented with life-threatening diseases and one of them died. This patient was the first fatal case (2.8%). Atypic and serous life-threatening presentations of rickettsioses must be kept in mind for the differential diagnosis of febrile disease in Turkey.

Meningitis due to bacillus anthracis.

The first case of haemorrhagic meningitis due to Bacillus anthracis in the European part of Turkey is reported here. B. anthracis, sensitive to penicillin, was isolated from the cerebrospinal fluid and blood cultures. Although appropriate therapy was administered, the patient died two days after hospitalization.

[Species and biovar distribution of Brucella isolates in Trakya University Hospital between 1997-2002]. / Trakya Universitesi Hastanesinde 1997-2002 yillari arasinda saptanan Brucella izolatlarinin tür ve biyovar dagilimi.

The aim of this study was to evaluate the species and biovar distribution of Brucella spp. isolated from blood cultures in Clinical Microbiology Laboratory of Trakya University Hospital, between 1997-2002. A total of 48 Brucella spp. have been isolated from 14.815 patients (0.3%), and the strains were identified according to CO2 requirement, H2S production, basic fuchsin and thionin sensitivity, lysis by Tbilisi phages, and presence of agglutination with monospecific A and M antisera. As a result, 47 (97.9%) isolates were identified as B. melitensis, and one as B. abortus (2.1%). Forty two (89.4%) of B. melitensis isolates were biovar 3, and five (10.6%) were biovar 1, while the single isolate of B. abortus was identified as an atypical strain.