Saim Dayan

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 microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study

We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p <0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p <0.05). Combination of L-J and ACS was superior to using these tests alone (p <0.05). There were poor and inverse agreements between EZNs and L-J culture (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -0.299, p <0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources.

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.

Management of Brucella endocarditis: results of the Gulhane study

Brucella endocarditis (BE) is a rare but life-threatening complication of human brucellosis. The aim of this study was to investigate the course of BE along with the therapeutic interrelations. A total of 53 patients with BE hospitalised in 19 health institutions between 2006 and 2011 were included in the Gulhane study. Diagnosis of brucellosis was established by either isolation of Brucella sp. or the presence of antibodies, and the definition of endocarditis was made according to Dukes criteria. There were four treatment groups: ceftriaxone combined with oral antibiotics (Group 1); aminoglycosides combined with oral antibiotics (Group 2); oral antibiotic combinations (Group 3); and aminoglycoside plus ceftriaxone combined with an oral antibiotic (Group 4). Involvement rates of the aortic, mitral and tricuspid valves were 49.1%, 43.4% and 5.7%, respectively. Thirty-two patients (60.4%) had an underlying cardiac valvular problem, including previous prosthetic valve replacement (n=18). Medical treatment was provided to 32 patients (60.4%), whilst concordant medical and surgical approaches were provided to 21 patients (39.6%). Mortality in Group 1 was 15% (3/20), whilst in Group 2 it was 5.3% (1/19). In Group 3, 25.0% (3/12) of the cases died, whereas none of the cases in Group 4 died. In conclusion, mortality increased 47-fold with pericardial effusion and 25-fold due to congestive heart failure that developed after BE. Although mortality was lower in the aminoglycoside-containing arm (Groups 2 and 4), statistical analysis could not be performed owing to the small number of patients.

Diagnosis of chronic brucellar meningitis and meningoencephalitis: the results of the Istanbul-2 study

No detailed data exist in the literature on the accurate diagnosis of chronic brucellar meningitis or meningoencephalitis. A multicentre retrospective chart review was performed at 19 health centres to determine sensitivities of the diagnostic tests. This study included 177 patients. The mean values of CSF biochemical test results were as follows: CSF protein, 330.64 ± 493.28 mg/dL; CSF/ blood-glucose ratio, 0.35 ± 0.16; CSF sodium, 140.61 ± 8.14 mMt; CSF leucocyte count, 215.99 ± 306.87. The sensitivities of the tests were as follows: serum standard tube agglutination (STA), 94%; cerebrospinal fluid (CSF) STA, 78%; serum Rose Bengal test (RBT), 96%; CSF RBT, 71%; automated blood culture, 37%; automated CSF culture, 25%; conventional CSF culture, 9%. The clinician should use every possible means to diagnose chronic neurobrucellosis. The high seropositivitiy in brucellar blood tests must facilitate the use of blood serology. Although STA should be preferred over RBT in CSF in probable neurobrucellosis other than the acute form of the disease, RBT is not as weak as expected. Moreover, automated culture systems should be applied when CSF culture is needed.

HBsAg, anti-HCV, anti-HIV 1/2 and syphilis seroprevalence in healthy volunteer blood donors in southeastern Anatolia

INTRODUCTION This study investigated the seroprevalence of hepatitis B virus surface antigen (HBsAg), antibody against hepatitis C virus (anti-HCV), antibody against human immunodeficiency virus type 1/2 (anti-HIV 1/2), and antibody against Treponema pallidum (anti-Treponemal or syphilis antibody) in healthy volunteer blood donors, and assessed their distribution according to the years and genders. METHODOLOGY HBsAg, anti-HCV, anti-HIV ½, and syphilis screening results of a total of 266,035 healthy volunteer blood donors who had been admitted for blood donation to the Regional Blood Center of Dicle University Hospital between January 2000 and December 2010 were evaluated, retrospectively. HBsAg, anti-HCV, and anti-HIV 1/2 screening were performed using a fully automated device with the microparticle enzyme immunoassay method (MEIA). Syphilis screening was performed by Rapid Plasma Reagin (RPR) carbon test between January 2000 and December 2009, and by using a fully automated device with the MEIA method between January 2010 and December 2010. RESULTS Of 266,035 healthy volunteer blood donors, 259,384 (97.5%) were male and 6,651 (2.5%) were female. Statistically, there was not any significant difference between male and female genders for HBsAg, anti-HCV and syphilis seropositivities (P = 0.729, P = 0.748, and P = 0.861, respectively). HBsAg was found to be positive in 8,422 (3.17%), anti-HCV in 1,703 (0.64%), anti-HIV 1/2 in one (0.0004%) of 266,035 healthy volunteer blood donors, and syphilis antibody with RPR in 166 (0.07%) of 246,341 healthy volunteer blood donors. CONCLUSION Blood donor forms should be carefully tailored to improve the identification of possible risks of transfusion-transmitted infections.

Analysis of antimicrobial consumption and cost in a teaching hospital

BACKGROUND The aim of this study is to compare the periods before and after the intervention applied using the ATC/DDD method in order to ascertain the rational use of antibiotics in a newly established hospital. METHOD The appropriateness of the hospitals antibiotic use, consumption rates and the costs were calculated and compared with other hospitals. Based on these data, an intervention has been planned in order to raise the quality of antibiotic use. The periods before and after the intervention were compared. Between 16 May 2011 and 23 May 2012, data were collected from all hospital units by the infectious diseases specialists and a point prevalence survey was conducted. Anatomical therapeutic chemical classification and the defined daily dose (DDD) methodology were used to calculate the antibiotic consumption. RESULTS On two specific days in 2011 and 2012, 194 out of 307 patients (63.2%) and 224 out of 412 patients (54.4%) received antibiotic treatment, respectively. In 2011 and 2012, the percentage of appropriate antibiotic use was 51% and 64.3%, respectively. Both in 2011 and 2012, inappropriate antibiotic use was found to be significantly higher in surgical clinics in comparison to the internal diseases clinics and the ICU. This was caused by the high rates of inappropriate perioperative antimicrobial prophylaxis observed in surgical clinics. During both years, approximately one-third of the antibiotics were prescribed for the purposes of perioperative prophylaxis, while 88.5% and 43.7% of these, respectively, were inappropriate and unnecessary. Cephalosporins, fluoroquinolones, combinations of penicillins (including β-lactamase inhibitors) and carbapenems were the most frequently prescribed antibiotics during the study periods. The mean total antibiotic consumption was 93.6 DDD/100 bed-days and 63.1 DDD/100 bed-days, respectively. The cost of total antibacterial consumption was € 7901.33 for all the patients (€ 40.72 per infected patient) and € 6500.26 (€ 29.01 per infected patient), respectively. CONCLUSION Each hospital should follow and assess their antibiotic use expressed in DDD in order to compare their antibiotic use with national and international hospitals (WHO, 2009 [14]).

Assessment of perioperative antimicrobial prophylaxis using ATC/DDD methodology

OBJECTIVES In the light of international experience and guidelines and in order to improve the quality of perioperative antimicrobial prophylaxis (PAP), various hospitals have set up their own multidisciplinary healthcare teams and have evaluated the density of PAP through close supervision and interventions. The aim of the present study was to compare the density, quality, and cost of PAP before and after an intervention implemented at our hospital in order to increase the quality of PAP. METHODS PAP was monitored using a form prepared in line with the international guidelines, which was completed by the infection control nurse under the supervision of the infectious diseases specialist. In order to reduce the frequent errors in our PAP procedures, an intervention was implemented, and the period before this intervention (January-April 2011) was compared with the post-intervention period 1 year later (January-April 2012). The density of PAP was calculated according to the Anatomical Therapeutic Chemical classification/defined daily dose (ATC/DDD) methodology. RESULTS A total of 2398 patients received PAP during this period. The most frequently used antibiotic before and after the intervention was cefazolin. Its use further increased after the intervention (p<0.001). After the intervention, the ratio of the correct timing of the first antibiotic dose increased from 91.7% to 99.0% (p<0.001), while the excessively long administration of PAP was reduced from 77.0% to 44.7% (p<0.001). The ratio of full compliance with the guidelines increased from 15.5% to 40.2% (p<0.001) and the rate of surgical site infections dropped from 18.5% to 12.0%. The density of antibiotic use dropped from 305.7 DDD/100 procedures=3.1 DDD/procedure to 162.1 DDD/100 procedures=1.6 DDD/procedure. CONCLUSION The quality of PAP may be improved through better compliance with healthcare guidelines, close supervision, and training activities. Also, surgical site infections and the cost of PAP may be reduced through more appropriate antibiotic use, thus contributing to the national healthcare budget.

Evaluation of cutaneous palpebral anthrax

Abstract Context: Anthrax is a rare disease caused by Bacillus anthracis. Antrax is zoonotic disease and is often encountered in persons engaged in animal husbandry. Cutaneous anthrax is approximately 95% of anthrax in humans. Palbebral involvement is rare. Objective: In this study, we aimed to evaluate the clinical presentation, diagnosis and treatment of cases with cutaneous palpebral anthrax. Methods: In this study, the patients diagnosed of cutaneous palpebral anthrax between January 2000 and December 2012, were investigated and evaluated, retrospectively. Cutaneous palpebral anthrax was diagnosed by the presence of typical anthrax lesion and/or observation of gram-positive encapsulated bacilli in gram prepations and/or culture positive of samples taken from lesions. In the cases who were culture-negative and without bacilli in gram-staining, the diagnosis was based on the presence of characteristic clinical presentation with a history of severe scarring formation, swelling, black eschar and positive response to the treatment. Results: A total of 21 patients with cutaneous palpebral anthrax admitted to the two hospitals between January 2000 and December 2012. Eight patients were male (38.1%) and 13 patients were female (61.9%), and the mean age was 31 ± 21.2 (range 1–82 years). The most common symptoms on admission to the hospital were swelling and redness on the skin. Periorbital lesions were in the right eye in 14 cases and the most common eyelid involvement was seen in upper eyelid with 15 cases. The diagnosis was based on isolation of bacteria in five (23.8%) cases, detection of gram-positive bacilli in direct examination of characteristic lesion material in six (28.5%) cases. Ten (47.7%) cases were diagnosed by the characteristic appearance of the lesion. Malignant pustule was seen in all of our patients and seven cases (33.4%) had malignant edema. In the treatment, penicilin was used for 10 (47.7%) cases, ampicillin-sulbactam for five (23.8%) cases and, ciprofloxacin for three (14.3%) cases. Cicatricial ectropion was observed in 10 (47.7%) patients, lagophthalmos developed in four (19%) patients, and corneal scar in two (9.5%) patients. The distribution of the cases did not differ by the year but showed a density in the months from July to September (62.7%). Conclusion: Early diagnosis and high dose antibiotic treatment can facilitate the treatment and prevent development of eyelid complications including cicatricial ectropion, corneal scars and palpebral symphysis. Prolonged follow-up is necessary in patients who develop complications and surgical intervention.

The Place and the Efficacy of Infectious Disease Consultations in the Hospitals

Abstract Our study aims to determine the efficacy of infectious disease consultations and the interrelations between doctors in this social laboratory. This study was conducted at 34 centers located in 22 cities across Turkey and contributed by 210 infectious disease specialists (IDSs) and 970 non–infectious disease specialists (NIDSs), totaling 1180 medical doctors. Infectious disease specialists and NIDSs have separately contributed by responding to questionnaires designed specifically for the consultation process. It appears that a satisfactory collaboration has been established between IDSs and NIDSs during the consultation practices. There are some discrepancies in the perceptions of some of the NIDSs. These are the evaluation of patients holistically, the expectation of NIDSs in critical infection cases to start the therapy immediately, losing the support of drug companies by NIDSs, and the restriction of NIDSs in routine medical practice. On the other hand, NIDSs seem to have real problems in the diagnosis or treatment of infectious diseases. The consultation service provided by the IDSs in Turkey is widely accepted among other clinicians and appears to be of a crucial importance.