Vedat Turhan

Efficacy and Tolerability of Antibiotic Combinations in Neurobrucellosis: Results of the Istanbul Study

ABSTRACT No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.

The implications of the presence of osteomyelitis on outcomes of infected diabetic foot wounds.

Abstract Aim: To assess the effect of the presence of osteomyelitis in patients with a diabetic foot infection. Methods: We reviewed the records of diabetic patients hospitalized at our medical center for a foot infection over a 2-y period. Using clinical, imaging, and microbiology results, we classified each patient as having diabetic foot osteomyelitis (DFO) or not. We then compared several outcome criteria of interest between the 2 groups. Results: Among 73 eligible patients, 37 were in the DFO group (DFO group), while the other 36 were in the soft tissue infection group (STI group). In comparison to the STI group, the DFO group had a significantly longer length of stay (LOS) in the hospital (42 (28.5–51) days vs 19.5 (13.2–29.5) days, p < 0.001), longer duration of antibiotic therapy (46.6 ± 19.9 days vs 22.0 ± 14.6 days, p < 0.001), longer duration of intravenous antibiotic therapy (32.3 ± 16.3 days vs 13.6 ± 14.3 days, p < 0.001), longer duration of wound before admission (44 (31–64.5) days vs 33 (23–45.5) days, p = 0.034), and longer time to wound healing (239.8 ± 108.2 days vs 183.1 ± 73 days, p = 0.011). There were more surgical procedures in the DFO group than in the STI group (24/37 (64.8%) vs 11/36 (30.5%), p = 0.003), and during hospitalization, 22 patients in the DFO group and 5 patients in STI group underwent minor amputation (59.4% vs 13.8%, p < 0.001). Conclusion: The presence of osteomyelitis negatively affects both the treatment and outcome of diabetic foot infections.

Nosocomial infection characteristics in a burn intensive care unit: Analysis of an eleven-year active surveillance

AIMS The objective of this study was to describe nosocomial infection (NI) rates, risk factors, etiologic agents, antibiotic susceptibility, invasive device utilization and invasive device associated infection rates in a burn intensive care unit (ICU) in Turkey. METHODS Prospective surveillance of nosocomial infections was performed according to Centers for Disease Control and Prevention (CDC) and National Healthcare Safety Network (NHSN) criteria between 2001 and 2012. The data was analyzed retrospectively. RESULTS During the study period 658 burn patients were admitted to our burn ICU. 469 cases acquired 602 NI for an overall NI rate of 23.1 per 1000 patient days. 109 of all the cases (16.5%) died. Pseudomonas aeruginosa (241), Acinetobacter baumannii (186) and Staphylococcus aureus (69) were the most common identified bacteria in 547 strains. CONCLUSION Total burn surface area, full thickness burn, older age, presence of inhalation injury were determined to be the significant risk factors for acquisition of NI. Determining the NI profile at a certain burn ICU can lead the medical staff apply the appropriate treatment regimen and limit the drug resistance. Eleven years surveillance report presented here provides a recent data about the risk factors of NI in a Turkish burn ICU.

How reliable are cultures of specimens from superficial swabs compared with those of deep tissue in patients with diabetic foot ulcers

PURPOSE To assess the reliability of cultures of superficial swabs (SS) by comparing them with cultures of concomitantly obtained deep tissue (DT) specimens in patients with diabetic foot ulcers. METHODS We reviewed clinical and microbiological data from patients with diabetes who presented during a two-year period to our hyperbaric medicine center with a foot ulcer. We identified patients who had at least one concomitantly collected SS and DT pair of specimens sent for culture. RESULTS A total of 89 culture pairs were available from 54 eligible patients, 33 (61.1%) of whom were hospitalized. Wounds were infected in 47 (87.0%) of the patients and 28 (51.9%) patients had received antibiotic therapy within the previous month. Overall, 65 (73%) of the SS and DT pairs had identical culture results, but in 11 (16.9%) cases the cultures were sterile; thus, only 54 (69.2%) of the 78 culture-positive pairs had identical results. Compared with DT, SS cultures yielded ≥1 extra organism in 10 (11.2%) cases, missed at least one organism in 8 (9.0%), and were completely different in 6 (6.7%). When compared to DT culture results, SS cultures had a positive predictive value of 84.4%, negative predictive value of 44.0%, and overall accuracy of 73.0%. CONCLUSIONS In patients with diabetic foot ulcers, results of specimens for culture taken by SS did not correlate well with those obtained by DT. This suggests that SS specimens may be less reliable for guiding antimicrobial therapy than DT specimens.

Increasing incidence of Gram-negative organisms in bacterial agents isolated from diabetic foot ulcers

INTRODUCTION In the present study, we sought to identify the bacterial organisms associated with diabetic foot infections (DFIs) and their antibiotic sensitivity profiles. METHODOLOGY We retrospectively reviewed the records of wound cultures collected from diabetic patients with foot infections between May 2005 and July 2010. RESULTS We identified a total of 298 culture specimens (165 [55%] wound swab, 108 [36%] tissue samples, and 25 [9%] bone samples) from 107 patients (74 [69%] males and 33 [31%] females, mean age 62 ± 13 yr) with a DFI. Among all cultures 83.5% (223/267) were monomicrobial and 16.4% (44/267) were polymicrobial. Gram-negative bacterial isolates (n = 191; 61.3%) significantly outnumbered Gram-positive isolates (n = 121; 38.7%). The most frequently isolated bacteria were Pseudomonas species (29.8%), Staphylococcus aureus (16.7%), Enterococcus species (11.5%), Escherichia coli (7.1%), and Enterobacter species (7.1%), respectively. While 13.2% of the Gram-negative isolates were inducible beta-lactamase positive, 44.2% of Staphylococcus aureus isolates were methicillin resistant. CONCLUSIONS Our results support the recent view that Gram-negative organisms, depending on the geographical location, may predominate in DFIs.

Mortality indicators in pneumococcal meningitis: therapeutic implications

BACKGROUND The aim of this study was to delineate mortality indicators in pneumococcal meningitis with special emphasis on therapeutic implications. METHODS This retrospective, multicenter cohort study involved a 15-year period (1998-2012). Culture-positive cases (n=306) were included solely from 38 centers. RESULTS Fifty-eight patients received ceftriaxone plus vancomycin empirically. The rest were given a third-generation cephalosporin alone. Overall, 246 (79.1%) isolates were found to be penicillin-susceptible, 38 (12.2%) strains were penicillin-resistant, and 22 (7.1%) were oxacillin-resistant (without further minimum inhibitory concentration testing for penicillin). Being a critical case (odds ratio (OR) 7.089, 95% confidence interval (CI) 3.230-15.557) and age over 50 years (OR 3.908, 95% CI 1.820-8.390) were independent predictors of mortality, while infection with a penicillin-susceptible isolate (OR 0.441, 95% CI 0.195-0.996) was found to be protective. Empirical vancomycin use did not provide significant benefit (OR 2.159, 95% CI 0.949-4.912). CONCLUSIONS Ceftriaxone alone is not adequate in the management of pneumococcal meningitis due to penicillin-resistant pneumococci, which is a major concern worldwide. Although vancomycin showed a trend towards improving the prognosis of pneumococcal meningitis, significant correlation in statistical terms could not be established in this study. Thus, further studies are needed for the optimization of pneumococcal meningitis treatment.

Hantavirus Infection in Istanbul, Turkey

To the Editor: More than 20 serotypes of hantavirus have been identified, and 11 infect humans. Puumala virus (PUUV), Dobrava virus (DOBV), and Seoul virus cause different forms of hemorrhagic renal syndrome (1,2). DOBV is endemic to Turkey and countries in the Balkan region. Approximately 10,000–12,000 cases of infection with PUUV and DOBV occur in European Russia each year (3). Initial case reports identified a hantavirus epidemic (laboratory confirmed) in February 2009 that involved 12 persons in Bartin and Zonguldak in western Turkey near the Black Sea. The hantavirus responsible for this epidemic was a PUUV subtype (4). We report a man infected with DOBV in Turkey who died 2 days after admission to an intensive care unit (ICU). The patient was a 22-year-old man who lived near Istanbul, Turkey. He was admitted to the Silivri State Hospital in March 2010 because of fatigue, diffuse pain, nausea, and vomiting. Approximately 2 hours after admission, ecchymotic rashes developed on his upper extremities and spread to other areas. His general condition worsened, and 15 hours later, he was transferred to the ICU of the Emergency Service of Gulhane Military Medical Academy Haydarpasa Training Hospital. His medical history did not include exposure to rodents or any travel. At admission to the ICU, his general condition was poor, and his speech was garbled and incoherent. He had a body temperature of 37.2°C, a pulse of 140 beats/min, an arterial blood pressure of 90/60 mm Hg, diffuse hemorrhagic foci, and a disseminated ecchymotic rash. Laboratory test results showed the following: 13,200 leukocytes/mm3, 92% polymorphonuclear leukocytes, hemoglobin 11.6 mg/dL, 385,000 platelets/mm3, alanine aminotransferase 62 IU/mL, aspartate aminotransferase 170 IU/mL, creatine phosphokinase 2,115 IU/L, lactate dehydrogenase 1,109 IU/L, urea 65 mg/dL, creatinine 3.78 mg/dL, prothrobin time 24.8 s, activated partial thromboplastin time 116.3 s, potassium 2.9 mEq/L, C-reactive protein 326 mg/dL, and erythrocyte sedimentation rate 132 mm/h. Subsequently, urinary output decreased and respiratory functions worsened. He then lost consciousness and was subjected to mechanic ventilation. Lumbar puncture was not performed because of risk for bleeding (high international normalized ratio values for blood coagulation and thrombocytopenia). Cranial computed tomographic scan did not show any pathologic changes. Treatment with ceftriaxone, 4 g/day intravenously, was initiated, and the dose was adjusted according to creatinine clearance because of suspected meningococcemia. A single dose of prednisolone, 80 mg intravenously, was given concomitantly. Bacterial growth was not observed in cultures of urine and blood samples. The Hanta Profile 1 EUROLINE Test (Euroimmun, Luebeck, Germany) was used to detect immunoglobulin (Ig) G and IgM against 3 hantavirus serotypes (PUUV, DOBV, and Hantaan virus). Results of a hantavirus IgM immunoblot test were positive for DOBV. The QIAamp viral RNA Mini Extraction Kit (QIAGEN, Hilden, Germany) was used for extraction of viral RNA. PUUV and DOBV RNA in serum and urine samples were investigated by using an in-house real-time PCR (Rotorgene; QIAGEN). DOBV RNA was detected in urine samples by PCR (Table). Table Detection of Dobrava virus in 22-year-old patient, Turkey* Meningococcemia, acute hemorrhagic fever, and Crimean-Congo hemorrhagic fever were considered in the differential diagnosis for the patient. Other diseases were excluded by biochemical, serologic, and microbiologic test results. Hantavirus infection was diagnosed in this patient on the basis of criteria recommended by the European Network for Diagnostics of Imported Viral Diseases (5). On the second day of treatment, the patient died of cardiopulmonary arrest. The patient had worked as a security guard in a new prison located in an area that had contained oak and hornbeam forests. DOBV is carried by rodents (Apodemus flavicollis), and the habitat of this rodent in Europe is open oak or beech forest. In a field study performed in rural areas of Turkey near the Black Sea and Aegean Sea, hantavirus was detected in Microtus spp. voles (6). In another study performed in regions near the Aegean Sea, DOBV was detected in 7 (3.5%) of 200 patients with acute or chronic renal failure (7). However, information about specific regions in Turkey in which hantavirus is endemic is limited. Hantavirus infections, which were first identified in northwestern Turkey in 2009 and subsequently in Istanbul, should be considered in the diagnosis of patients who have fever and bleeding. Because of recent emergence of hantavirus in Turkey, areas to which this virus is endemic and where risk for infection is highest have not been identified. Therefore, all inhabitants at high risk for infection (forest workers, military personnel, farmers, persons living in or near a forest, persons handling wood) should be informed about this risk.

Ribavirin is not effective against Crimean-Congo hemorrhagic fever: observations from the Turkish experience.

Summary Crimean–Congo hemorrhagic fever (CCHF) is a viral infection associated with a high mortality rate. Ribavirin is the only drug used in the treatment of this disease. Studies investigating the effectiveness of ribavirin in CCHF have been retrospective and to date have included only a small number of cases. In recent years, due to climate changes, the number of cases of CCHF in Turkey has increased, and experience in the treatment of CCHF has improved. Several studies have evaluated the efficacy of ribavirin in Turkey, including one randomized controlled trial and two studies with a large number of cases. In these studies, ribavirin therapy was not shown to decrease mortality rates; the mortality rate was 2–9% in patients treated with ribavirin and 5.6–11% in those who were not treated with this drug. These findings suggest that patients with CCHF should be followed with supportive care only until randomized controlled trials with larger groups have been conducted.

Performance of the probe-to-bone test in a population suspected of having osteomyelitis of the foot in diabetes.

BACKGROUND We investigated the validity of probe-to-bone testing in the diagnosis of osteomyelitis in a selected subgroup of patients clinically suspected of having diabetic foot osteomyelitis. METHODS Between January 1, 2007, and December 31, 2008, inpatients and outpatients with a diabetic foot ulcer were prospectively evaluated, and those having a clinical diagnosis of foot infection and at least one of the osteomyelitis clinical suspicion criteria were consecutively included in this study. RESULTS Sixty-five patients met the inclusion criteria and were prospectively enrolled in the study. Forty-nine patients (75.4%) were hospitalized, and the remaining 16 (24.6%) were followed as outpatients. Osteomyelitis was diagnosed in 39 patients (60.0%). Probe-to-bone test results were positive in 30 patients (46.1%). The positive predictive value for the probe-to-bone test was fairly high (87%), but the negative predictive value was only 62%. The sensitivity and specificity of the test were 66% and 84%, respectively. White blood cell counts and mean C-reactive protein levels did not statistically significantly differ between groups. However, erythrocyte sedimentation rates greater than 70 mm/h reached statistical significance between groups. Wound area and depth were not found to be statistically significantly different between groups. CONCLUSIONS Positive probe-to-bone test results and erythrocyte sedimentation rates greater than 70 mm/h provide some support for the diagnosis of diabetic foot osteomyelitis, but it is not strong; magnetic resonance imaging or bone biopsy will probably be required in cases of doubt.

Hyperbaric Oxygen as Adjunctive Therapy in Experimental Mediastinitis

BACKGROUND Mediastinitis is a dreaded complication of cardiac surgical procedures. The purpose of our study was to research the role of hyperbaric oxygen therapy (HBO) in the treatment of experimental mediastinitis and to investigate whether it potentiates the antibiotic effects of linezolid, teicoplanin, and vancomycin. METHODS The study included nine groups; an uncontaminated and a contaminated untreated control groups, and seven contaminated groups that received HBO or systemic antibiotics with linezolid, vancomycin, or teicoplanin, or a combination therapy consisting of one of these antibiotics and HBO. There were six adult male Wistar rats in each group. Contaminated groups were inoculated with 0.5 mL 10(8) CFU/mL methicillin resistant Staphylococcus aureus in the mediastinal and in the sternal layers. The antibiotic treatment continued 7 d. Twelve hours later at the end of the treatment, the rats were sacrificed, a sternotomy was performed for each rat and tissue samples from the upper ends of the sternum were aseptically obtained and evaluated microbiologically. RESULTS There was no difference between the therapeutic efficacy of linezolid, teicoplanin, or vancomycin (P>0.05). When the groups were analyzed separately, treatment with a combination of HBO and antibiotic therapy reduced the bacterial count in comparison with HBO or antibiotic treatment alone (P<0.05). The combination of teicoplanin or vancomycin and HBO, respectively, was not more effective in reducing the bacterial count in comparison with the combination of linezolid and HBO (P>0.05). CONCLUSIONS Linezolid and teicoplanin therapy was found as effective as standard vancomycin therapy for methicillin resistant Staphylococcus aureus (MRSA) mediastinitis. Adjunctive HBO offered additional benefit to the antibiotic treatment of mediastinitis.