Murat Dizbay

Colistin and tigecycline susceptibility among multidrug-resistant Acinetobacter baumannii isolated from ventilator-associated pneumonia

Multidrug-resistant (MDR) Acinetobacter baumannii is one of the most important pathogens in intensive care units related to morbidity and mortality, especially in ventilator-associated pneumonia (VAP). In this study, 80.5% of isolates were MDR. The antimicrobial susceptibilities for 12 different antibiotics of MDR A. baumannii isolated from VAP were tested. Among the MDR A. baumannii isolates, resistance rates were found to be 95.5%, 72.7%, 80.3%, 71.2% and 68.2% for ciprofloxacin, cefepime, imipenem, meropenem and cefoperazone/sulbactam, respectively. Netilmicin resistance was detected in 30.3% of the isolates. Resistance rates for colistin and tigecycline were 0% and 25.8%, respectively. It is obvious that new alternative drugs are needed for the treatment of MDR A. baumannii-related VAP owing to high resistance to carbapenems, quinolones, aminoglycosides and cefoperazone/sulbactam. Although colistin appears to be a good choice, adverse reactions and unavailability of colistin limit its wide usage in Turkey. Tigecycline, which will shortly be introduced commercially in Turkey, is very effective against MDR A. baumannii isolates and shows promising results to solve the problem, however resistance rates should be monitored closely.

Nosocomial imipenem-resistant Acinetobacter baumannii infections: Epidemiology and risk factors

Abstract The incidence, clinical characteristics, risk factors, antimicrobial susceptibility, and outcomes of nosocomial imipenem-resistant A. baumannii (IRAB) infections during a 5-y period (2003–2007) were retrospectively analyzed. A total of 720 patients with 925 episodes of A. baumannii infection were included in the study. A. baumannii infections were seen mostly in intensive care units. The incidence was 6.2 per 1000 admissions. The most common infections were pneumonias and bloodstream infections. Imipenem resistance among Acinetobacter strains increased significantly each y of the study (from 43.3% to 72.9%). Mortality was related to the presence of imipenem resistance, stay in intensive care unit, female gender, old age, and pneumonia. Haemodialysis, malignancy, and mechanical ventilation were significant risk factors for IRAB infections. Imipenem resistance was higher in strains isolated from patients with pneumonia. IRAB strains showed higher resistance rates to other antibiotics than imipenem-susceptible strains. The most active antimicrobial agents against A. baumannii were cefoperazone–sulbactam and netilmicin. The incidence of A. baumannii infections and imipenem resistance increased during the study period. IRAB infections should be considered in patients on mechanical ventilation and haemodialysis and in patients with malignancies.

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.

In vitro synergistic activity of tigecycline and colistin against XDR-Acinetobacter baumannii

The emergence of extensive drug-resistant (XDR) Acinetobacter baumannii limits the therapeutic options and leads to high mortality in intensive care units. Combined antibiotic therapy is frequently recommended for the treatment of these infections. Colistin (CO) and tigecycline (TIG), alone or in combination with other antimicrobials, are the most commonly used antibiotics in the treatment of these resistant infections. In this study, the in vitro synergistic activity of TIG and CO were tested for 25 XDR-A. baumannii strains isolated from ventilator-associated pneumonia by the Etest method. Resistance to CO was not detected, whereas 8% of the strains were resistant to TIG. The TIG–CO combination was more synergistic than TIG–rifampin and CO–rifampin according to the fractional inhibitory concentration index. No antagonism was detected between the drugs in the study. There was no strong correlation between the activity of the combinations with reference to strains or genotypes. Our results suggest that the combined use of TIG and CO may be useful for the treatment of XDR-A. baumannii infections.

Acinetobacter baumannii infection in patients with hematologic malignancies in intensive care unit: Risk factors and impact on mortality ☆

PURPOSE We investigated the characteristics of Acinetobacter baumannii infection in critically ill patients with hematologic malignancies. MATERIALS AND METHODS The prospectively collected data of patients with hematologic malignancies admitted to a medical intensive care unit of a university hospital from 2007 through 2010 were reviewed retrospectively. RESULTS One hundred twenty-eight patients were included in the study, among whom 35 (27%) developed 39 A baumannii infections. Pneumonia was the most common infection site of A baumannii. Presence of neutropenia, underlying hematologic malignancy, and the disease status did not affect the acquisition of the infection. Advancing age, prior exposure to aminoglycosides, central venous catheterization, and presence of nasogastric tube were the independent risk factors for the development of A baumannii infections. The mortality rate was higher in patients with A baumannii infections compared with the ones without (P = .009). However, in multivariate analysis, low Glasgow coma scale, prior immunosuppressive treatment, neutropenia, invasive mechanical ventilation, and severe sepsis were independently associated with mortality, whereas presence of A baumannii infection was not. CONCLUSIONS Despite the high mortality rate in critically ill patients with hematologic malignancies, presence of A baumannii infection was not an independent risk factor for mortality.

High incidence of Candida parapsilosis candidaemia in non-neutropenic critically ill patients: epidemiology and antifungal susceptibility.

Abstract The epidemiological and antifungal susceptibility data for 35 episodes of candidemia in intensive care units (ICU) in 2007 were evaluated by prospective active surveillance. The incidence of fungaemia was 39.1 cases per 1000 ICU admissions and 2.85 cases per 1000 patient-days. The crude mortality was 65.7%; 70.8% of the fatalities occurred within 7 days of admission to the ICU. Only 2 species were isolated, Candida parapsilosis (77.1%) and Candida albicans (22.9%). There was no association between mortality and patient characteristics, prior antifungal usage, Candida subspecies or antifungal resistance (p > 0.05). Of the isolates, 5.7% were resistant to fluconazole and caspofungin, and 3.4% to voriconazole and amphotericin B. In molecular analysis of the isolates, 2 clusters of C. parapsilosis in the neurology and anaesthesiology ICUs were detected by randomly amplified polymorphic DNA (RAPD), suggesting a nosocomial transmission. In conclusion, a high incidence and high mortality rate of C. parapsilosis candidaemia were found in the ICUs. An excessive use of invasive procedures, total parenteral nutrition and broad-spectrum antibiotics in the ICUs, combined with a lack of proper infection control measures, may possibly explain the high incidence of C. parapsilosis candidaemia in our hospital.

Nosocomial fungemia due to Trichosporon asteroides: firstly described bloodstream infection

Trichosporon spp. are oppurtunistic yeasts that cause deep-seated, mucosa-associated, and superficial infections in immunocompromised patients. It is well known that Trichosporon asteroides is mainly responsible of superficial infections and does not cause systemic infections in humans so far. In this study, we present the first case of disseminated infection due to Trichosporon asteroides in an intensive care patient. Yeast colonies were isolated from the specimens of blood, urine, aspiration fluid of the endotracheal tube and catheter tip swabs of the patient. Conventional mycological studies were not adequate for the identification of the isolate to the species level. The genetic identification of the yeast isolate was performed and the DNA sequence of the isolate exactly matched the corresponding sequence of the Trichosporon asteroides rRNA gene from the GenBank DNA database (accession numbers: AB018017, AF075513). Therefore, our isolate was identified as Trichosporon asteroides as a causative agent of deep-seated fungemia.

Molecular investigation of a fungemia outbreak due to Candida parapsilosis in an intensive care unit

We investigated a nosocomial cluster of four Candida parapsilosis fungemia episodes that occurred in a neurological intensive care unit over a two-week period. The four infected patients had received parenteral nutrition through central lines, and all four had catheter-related candidemia. All of the isolates were susceptible to all of the antifungals tested, including amphotericin B, fluconazole, voriconazole, and caspofungin. They had strictly related fingerprints, based on randomly amplified polymorphic DNA analysis. Additional DNA sequencing data revealed that they were same strain. Although no isolate of Candida parapsilosis was recovered from other clinical, surveillance, or environmental samples, nosocomial spread of this yeast ceased, following the reinforcement of infection-control measures. Candida parapsilosis may require an intravascular foreign body to cause fungemia, but this outbreak shows that it can be transmitted nosocomially and can cause epidemics.

Tigecycline: Its potential for treatment of brucellosis

The in vitro efficacy and synergistic activity of tigecycline in comparison with other antimicrobials used in brucellosis, were tested for 16 Brucella melitensis strains by the E-test method. Tigecycline had the lowest minimal inhibitory concentration levels, and rifampin the highest, in the study. Tigecycline also provided the better synergistic activity compared to doxycycline according to the fractional inhibitory concentration index. The results of this in vitro study suggest tigecycline as a therapeutic alternative for brucellosis. These observations need to be supported with clinical studies.

Colistin therapy in critically ill patients with chronic renal failure and its effect on development of renal dysfunction

Recently, colistin has become a salvage therapy in the treatment of serious Intensive Care Unit infections owing to the emergence of extensively drug-resistant (XDR) bacterial isolates. This study aimed to show the effectiveness of colistin in critically ill patients with renal failure. A prospective case-control study of 94 patients admitted to medical intensive care units of a university hospital from December 2008 to June 2010 was conducted. All patients had infections with XDR Acinetobacter baumannii or Pseudomonas aeruginosa and received colistin. Cases comprised 39 patients with chronic renal failure (CRF) and controls were other patients without CRF. Apart from the male dominancy in the CRF group, there was no statistical difference between the two groups regarding demographic characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and site and type of infection. In patients who completed colistin therapy, bacteriological cure was seen in 87% of patients with CRF and 95% of patients without CRF (P=0.890). Mortality in patients with CRF was similar to that in patients without CRF (44% and 42%, respectively) (P=0.999). Nephrotoxicity developed in 23.6% of patients in the control group. Concomitant nephrotoxic agents and total defined daily dose of colistin did not affect the development of nephrotoxicity. The mortality rate was 38% in patients with nephrotoxicity, similar to the mortality rate in patients without nephrotoxicity (36%) (P=0.999). In conclusion, in critically ill patients with CRF, colistin therapy, although used at a reduced dosage, was as effective as in patients without CRF.