Mortality predictors of Staphylococcus aureus bacteremia: a prospective multicenter study.

BACKGROUND: Staphylococcus aureus is one of the causes of both community and healthcare-associated bacteremia. The attributable mortality of S. aureus bacteremia (SAB) is still higher and predictors for mortality and clinical outcomes of this condition are need to be clarified. In this prospective observational study, we aimed to examine the predictive factors for mortality in patients with SAB in eight Turkish tertiary care hospitals. METHODS: Adult patients with signs and symptoms of bacteremia with positive blood cultures for S. aureus were included. All data for episodes of SAB including demographics, clinical and laboratory findings, antibiotics, and outcome were recorded for a 3-year (2010-2012) period. Cox proportional hazard model with forward selection was used to assess the independent effect of risk factors on mortality. A 28-day mortality was the dependent variable in the Cox regression analysis. RESULTS: A total of 255 episodes of SAB were enrolled. The median age of the patients was 59 years. Fifty-five percent of the episodes were considered as primary SAB and vascular catheter was the source of 42.1 %. Healthcare associated SAB was defined in 55.7 %. Blood cultures yielded methicillin-resistant S. aureus (MRSA) as a cause of SAB in 39.2 %. Initial empirical therapy was inappropriate in 28.2 %. Although overall mortality was observed in 52 (20.4 %), 28-day mortality rate was 15.3 %. Both the numbers of initial inappropriate empirical antibiotic treatment and the median hours to start an appropriate antibiotic between the cases of fatal outcome and survivors after fever onset were found to be similar (12/39 vs 60/216 and 6 vs 12 h, respectively; p > 0.05). High Charlson comorbidity index (CCI) score (p = 0.002), MRSA (p = 0.017), intensive care unit (ICU) admission (p < 0.001) and prior exposure to antibiotics (p = 0.002) all were significantly associated with mortality. The Cox analysis defined age [Hazard Ratio (HR) 1.03; p = 0.023], ICU admission (HR 6.9; p = 0.002), and high CCI score (HR 1.32; p = 0.002) as the independent predictive factors mortality. CONCLUSIONS: The results of this prospective study showed that age, ICU stay and high CCI score of a patient were the independent predictors of mortality and MRSA was also significantly associated with mortality in SAB.

Efficacy and tolerability of antibiotic combinations in neurobrucellosis: results of the Istanbul study.

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.

[Prospective evaluation of the risk factors, etiology and the antimicrobial susceptibilities of the isolates in nosocomial bacteremic patients]. / Nozokomiyal bakteriyemili hastalarda risk faktörleri, etiyoloji ve izole edilen etkenlerin antibiyotik duyarliliklarinin prospektif olarak degerlendirilmesi.

This study was aimed to assess the frequency, risk factors and etiology of bacteremia and antimicrobial susceptibilities of strains isolated from adult bacteremic patients hospitalized in Kocaeli University Hospital, Turkey during a 12-month period. Blood specimens obtained from a total of 2602 patients after at least 48 hours of hospitalization, were cultured in aerobic BACTEC 9120 and BACTEC 9050 (Becton-Dickinson, USA) automatized systems, and the identification and antibiotic susceptibilities of bacteria were performed by VITEK 1 (bioMerieux, France) system. Blood cultures of a total of 385 (14.7%) patients yielded bacterial growth; the contamination rate being 9.1% (238/2602) and nosocomial bacteria rate being 5.6% (147/2602). The distribution of the 147 (81 female, 67 male) bacteremic patients were as follows: 45% internal ward, 28% surgical ward and 27% intensive care unit. A total of 148 patients (81 female, 67 male) with no growth in their blood cultures were randomly chosen as the control group. The pathogens isolated from nosocomial bacteremias revealed 101 gram-positive bacteria (68.7%), 39 gram- negative bacilli (26.5%) and seven Candida species (4.7%). The most frequent gram-positive bacteria were staphylococci 84/101; 83.1%) and gram-negative bacteria were E. coli (14/39; 35.8%). Coagulase negative staphylococci (CNS) were isolated from 79% of the cultures evaluated as contaminants. Methicillin resistance was determined in 61.6% of S. aureus and 68.1% of CNS. Extended spectrum beta-lactamases were detected in 64% of E. coli, 62% of Pseudomonas spp., 47% of Klebsiella spp. and 24% of Acinetobacter spp. and resistance rates to ceftazidime and beta-lactam/beta-lactamase inhibitor combinations in these strains were 39-67%. The most effective drug group was found to be carbapenems with 3-26% resistance rates. The evalution of risk factors between patient and control groups revealed that mechanical ventilation (p < 0.05) and interventional catheters (except for intravenous catheters) (p < 0.05) were the most frequent sources of bacteremias. The most frequent focus of infection were the lungs (29.9%), followed by abdominal and catheter originated infections (23.8% each). The high rate of antibiotic resistance determined in the nosocomial bacterial isolates in our hospital indicated that antibiotic use policies in our setting should be taken under control. The high rate of contamination in blood cultures emphasize that more attention should paid for continous education about collection of blood culture specimens.

[Pulmonary nocardiosis with a large solitary cavitary nodule caused by Nocardia cyriacigeorgica in a patient receiving corticosteroid therapy]. / Kortikosteroid tedavisi alan hastada Nocardia cyriacigeorgica'nin neden oldugu soliter kaviter nodül yapan pulmoner nokardiyoz.

Nocardiosis is a rare disease generally caused by members of Nocardia asteroides complex, particularly in immunosupressed patients. Nocardia cyriacigeorgica is a newly described member of this complex. In this article, a case of pulmonary nocardiosis with a large solitary cavitary nodule caused by N. cyriacigeorgica, in a patient receiving corticosteroid therapy was presented. A 29 years old male patient receiving prednisolone for 5 months was admitted to our hospital with fever, cough, right thoracic pain and night sweats. Computed tomography scan of chest demonstrated a large solitary cavitary nodule in the right lower lobe. Gram stained smear of the sputum revealed gram-positive, beaded, branched filamentous bacilli. On the third day of his admission, a catalase positive, oxidase negative and immotile bacilli, compatible with Nocardia spp., were isolated from the sputum sample taken at the day of admission. The isolated bacterium was identified as N. cyriacigeorgica by reference laboratory (Lyon, France). Oral trimethoprim (320 mg/day) and sulfamethoxazole (1600 mg/day) therapy given for three months, resulted in complete cure of the lesion without any sequela. This was the fourth case of pulmonary nocardiosis caused by N. cyriacigeorgica reported from Turkey. Microbiological examination of sputum is the most important tool for the diagnosis. Treatment with appropriate antibiotics may achieve complete cure even in large cavitary lesions. In conclusion, pulmonary nocardiosis should be considered in differential diagnosis of solitary cavitary nodules, especially in immunocompromised patients.

Effect of vancomycin, teicoplanin, and cefuroxime on Staphylococcus epidermidis adherence to intraocular lenses.

PURPOSE: To compare the adherence of Staphylococcus epidermidis on AcrySof (Alcon) and poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) treated with vancomycin, teicoplanin, and cefuroxime. SETTING: Kocaeli University, School of Medicine, Kocaeli, Turkey. METHODS: The lenses were contaminated with S epidermidis solutions containing 10(8) colony-forming units. Intraocular lenses were placed in sterile triptic soy broth after being held in antibiotic solutions for 15 minutes. After that, sonication and vortex procedures were performed to remove all the attached bacteria that could not be removed by antibiotics. Ten microliters from each broth were taken and inoculated into sheep blood agar. The colonies were counted overnight. The statistical analyses were made using Mann-Whitney U and Kruskal-Wallis tests, and a P value less than 0.05 was considered statistically significant. RESULTS: Regarding the inhibitory effect of antibiotics on bacterial adhesion, there was no statistically significant difference between AcrySof and PMMA lenses. In the cefuroxime group, the mean numbers of colony-forming units on AcrySof and PMMA lenses were 35.2 +/- 6.94 and 30.8 +/- 18.69, respectively (P>.05). In the teicoplanin group, the mean number of colony-forming units on AcrySof lenses was 100.1 +/- 20.97 and 70.6 +/- 43.75 on the PMMA lenses. The adherence in the vancomycin group was 245 +/- 273.74 colony-forming units for AcrySof lenses and 159.8 +/- 101.94 for PMMA lenses (P>.05). Regarding the inhibitory effect of antibiotics, cefuroxime was the most effective, followed by teicoplanin and vancomycin, respectively. Overall, the mean numbers of colony-forming units on the lenses that were held in cefuroxime, teicoplanin, and vancomycin solutions were 33.0 +/- 13.90, 85.35 +/- 36.66, and 202.4 +/- 205.74, respectively (P = .000). CONCLUSIONS: The results suggest that cefuroxime, teicoplanin, and vancomycin significantly inhibit bacterial adherence to IOLs. The effect of cefuroxime on adherence inhibition was significantly higher than that of teicoplanin and vancomycin. Bacterial adherence is an important factor in bacterial virulence. Antibiotics, especially cefuroxime, can successfully inhibit bacterial adherence.

An outbreak of SHV-5 producing Klebsiella pneumoniae in a neonatal intensive care unit; meropenem failed to avoid fecal colonization.

An outbreak of extended-spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae (ESBL-Kp) in a neonatal intensive care unit prompted a prospective surveillance study between 12th September and 6th October 2003. Surveillance was carried out by obtaining stool samples twice a week. The DNA relatedness of the isolates was shown by random amplified polymorphic DNA comparison (ERIC-PCR). ESBL production was identified by clavulanate synergy, isoelectric focusing, PCR and sequence analysis. During the study period, 49 neonates were hospitalized in the neonatal intensive care unit (NICU). In the first 20-day period, five neonates were infected with ESBL-Kp. The first patient treated with third generation cephalosporin and the second patient treated with meropenem died. While all three infected survivors were clinically improving, the digestive tracts were being colonized by SHV-5 producing Klebsiella. In the next period of the study, five neonates were colonized by ESBL-Kp as well. Univariate comparison of risk factors between colonized and non-colonized neonates was not significant. A total of 24 colonally related ESBL-Kp have been recovered from clinical materials and stool samples. This study demonstrated that parenterally applied meropenem, though successful in treating the systemic illness, might fail to protect the digestive tract from colonization of ESBL-Kp.

A national survey of surgical antibiotic prophylaxis in Turkey.

OBJECTIVE: To assess the quality of antibiotic prophylaxis for clean and clean-contaminated elective surgical procedures. DESIGN: A cross-sectional, country-wide survey. SETTING: Thirty-six hospitals in 12 cities in Turkey. PARTICIPANTS: Four hundred thirty-nine surgeons from 6 different specialties who performed selected procedures of interest. METHODS: A random sample of surgeons from different hospitals was selected. A standardized data collection form was used to record the type of procedure, the names, doses, timing of the first doses, and duration of antibiotics, important decisive factors, and problems in the management of prophylactic antibiotic use for surgical procedures. RESULTS: Fifty-five percent of surgeons addressed completed the survey. For clean-contaminated procedures, 6% of surgeons did not use antibiotic prophylaxis, whereas 88% used more than a single dose. Inappropriate antibiotics were chosen for 32% of procedures. In 39% of procedures, the first dose of antibiotics was not administered during induction of anesthesia. Duration of prophylaxis was longer than 24 hours in 80% and longer than 48 hours in 46% of all procedures. Only 112 surgeons (26%) were using definitely appropriate prophylaxis in all ways. Multivariate analysis revealed that surgeons in university hospitals (OR, 2.353; CI95, 1.426-3.884; P = .001) and general surgeons (OR, 4.986; CI95, 2.890-8.604; P < .001) used antibiotic prophylaxis more appropriately. Patients not covered by health insurance (OR, 0.417; CI95 0.225-0.772; P < .001) were associated with inappropriate prophylaxis. CONCLUSION: Given the high frequency of antibiotics prescribed for surgical prophylaxis in Turkey, adherence to surgical prophylaxis guidelines is urgently needed.

Expression stability of six housekeeping genes: A proposal for resistance gene quantification studies of Pseudomonas aeruginosa by real-time quantitative RT-PCR.

Constantly expressed genes are used as internal controls in relative quantification studies. Suitable internal controls for such studies have not yet been defined for Pseudomonas aeruginosa. In this study, the genes ampC, fabD, proC, pbp-2, rpoD and rpoS of P. aeruginosa were compared in terms of expression stability by real-time quantitative RT-PCR. A total of 23 strains with diverse resistance phenotypes were studied. Stability of expression among the housekeeping genes was assessed on the basis of correlation coefficients, with the best-correlated pair accepted as being the most stable one. Eventually, proC and rpoD formed the most stable pair (r = 0.958; P < 0.001). Next, in four ciprofloxacin-selected nfxC-like mutants, levels of oprD, oprM and oprN mRNA were compared with those of their wild-type counterparts. The comparison was made after correcting the raw values by the geometric mean of the internal control genes proC and rpoD. The level of oprN mRNA was significantly up-regulated, while the oprD gene was down-regulated (although this difference was statistically insignificant), in the mutants. This expression pattern was consistent with that of the expected expression profile of nfxC-type mutants; this experiment therefore lends further support to the use of proC and rpoD genes simultaneously as internal controls for such studies.

Comparison in a rat thigh abscess model of imipenem, meropenem and cefoperazone-sulbactam against Acinetobacter baumannii strains in terms of bactericidal efficacy and resistance selection.

BACKGROUND: We compared imipenem, meropenem and cefoperazone-sulbactam against hospital originated A. baumannii strains in terms of bactericidal efficacy and selection of resistant mutants during treatment in a rat thigh abscess model. METHODS: A total of 18 strains were inoculated in 54 animals (one strain for three animals). Randomly selected 10 among these 18 strains were inoculated in another 10 rats as the control group. Imipenem, meropenem and cefoperazone-sulbactam were the antibiotics compared. After four days of treatment, Wistar albino rats (200 to 250 g) were sacrificed and the abscess materials were processed for mean colony counts and for the presence of resistant mutants. RESULTS: The mean CFUs per gram (mean +/- (std. deviation) [x10(4)]) of the abscess were: 9,14 (25,24), 2,11 (3,78), 1,20 (1,70) in the imipenem (n = 17), meropenem (n = 18) and cefoperazone-sulbactam (n = 17) groups, respectively. The differences were not significant. On the other hand, no resistant mutant was detected in abscess materials. CONCLUSION: This study indicated; first, cefoperazone-sulbactam is comparable to carbapenems in bactericidal efficacy in this particular abscess model and second, emergence of resistance due to spontaneous mutations is not at least a frequent phenomenon among A. baumannii.

Isolated necrotizing epiglottitis: report of a case in a neutropenic patient and review of the literature.

Isolated necrotizing epiglottitis (INE) is an unusual condition that may develop in immunocompromised patients. Only 3 cases of INE have been reported in the English-language literature; this is the fourth case, one in a 27-year-old woman who had neutropenia due to cytomegalovirus infection. Stenotrophomonas maltophilia and Candida albicans were isolated from the culture of necrotic material. The features of INE are discussed here by reviewing the literature and by examining the characteristics of this case.

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.

Genetic and enzymatic properties of metallo-beta-lactamase VIM-5 from a clinical isolate of Enterobacter cloacae.

A VIM-5-producing Enterobacter cloacae isolate (EDV/1) was identified in a collection of clinical strains stored before 2002. The gene, bla(VIM-5), was located on a 2,712-bp BamHI-HindIII fragment of a 23-kbp (approximately) nonconjugative plasmid (pEDV5) in a class 1 integron as a single gene cassette.