Extensively drug-resistant Acinetobacter baumannii bacteraemia in a multidisciplinary intensive care unit during a 6-year period: Risk factors for fulminant sepsis.

OBJECTIVES: This study aimed to determine potential host-, pathogen-, infection- and treatment-related risk factors that might predict a fulminant fatal course of bacteraemia caused by extensively drug-resistant Acinetobacter baumannii (XDR-Aba). METHODS: Eighty-seven patients with monomicrobial growth of XDR-Aba in blood cultures within a 6-year period (2011-2016) were studied. Patients were divided into three groups according to ICU outcome: Group A (n=40) consisted of patients who survived; Group B (n=10) included patients with fulminant sepsis who died early (≤48h); and Group C (n=37) included patients who died later (>48h) after the onset of bacteraemia. RESULTS: Regarding patient co-morbidities, patients who died from fulminant XDR-Aba bacteraemia had a significantly higher prevalence of chronic renal failure compared with patients who survived (40.0% vs. 7.5%; P=0.029). Patients with fulminant sepsis showed more severe organ dysfunction based on SOFA score compared with survivors (10.83±2.93 vs. 6.65±3.6; P=0.013). The primary to secondary bacteraemia ratio and appropriate treatment were similar among the three outcome groups. Patients with fulminant bacteraemia displayed higher rates of colistin-, tigecycline- and pandrug-resistant strains, although not statistically significant. CONCLUSIONS: Patients suffering from a fulminant course of XDR-Aba bacteraemia showed significantly higher rates of chronic renal failure and multiple organ dysfunction. Resistance patterns of XDR-Aba isolates and receipt of appropriate treatment did not affect outcomes. Further studies including larger samples of patients along with investigation of specific virulence determinants of individual Aba strains are needed.

Sequence-based identification, genotyping and EUCAST antifungal susceptibilities of Trichosporon clinical isolates from Greece.

Trichosporon yeasts constitute emerging pathogens, implicated in organ-specific and systemic infections. In this first, comprehensive study of Trichosporon clinical isolates in Greece, 42 isolates were identified by sequencing the hypervariable D1/D2 domain of the Large Subunit (LSU) rDNA gene, while Trichosporon asahii were genotyped by sequencing the Intergenic Spacer 1 region, and antifungal susceptibilities were determined by the EDef 7.2 (EUCAST) method, in parallel with the CLSI standard. Trichosporon asahii was the primary species (37 isolates) followed by Trichosporon coremiiforme, Trichosporon dermatis, Trichosporon loubieri and Trichosporon mycotoxinivorans. One strain remained unidentified. Seven T. asahii genotypes were recorded. The major genotypes were: genotypes 4 (29%) and 3 (26%) followed by 1, 5 and 7 (9.5% each). Two novel genotypes were identified designated as 10 and 11. EUCAST MIC ≥2 mg/L was recorded in 58% of the isolates (amphotericin B), 41% (itraconazole), 41% (posaconazole) and 38% (voriconazole). Fluconazole MICs of ≥32 mg/L were recorded in 23.8% of the isolates. Analysis of variance performed on absolute values showed that the amphotericin B, itraconazole, posaconazole and voriconazole MICs of T. asahii were equivalent. Typically higher MIC values were displayed by fluconazole. Antifungal susceptibilities of the seven different genotypes were homogeneous. Agreements between EUCAST and CLSI ranged from 88.1 to 97.62%. Overall, the high MICs recorded among the Trichosporon isolates for all tested drugs justify routine susceptibility testing of clinical isolates.

Carbapenem-resistant versus carbapenem-susceptible Acinetobacter baumannii bacteremia in a Greek intensive care unit: risk factors, clinical features and outcomes.

BACKGROUND: There has been an increasing incidence of carbapenem-resistant Acinetobacter baumannii (CRAB) infections in recent years. The objective of this study was to determine specific risk factors for and outcome of bacteremia due to CRAB isolates among our ICU patients with A. baumannii bacteremia. PATIENTS AND METHODS: Among 96 patients with ICU-acquired A. baumannii bacteremia, 30 patients with CRAB were compared with the remaining 66 with carbapenem-susceptible A. baumannii (CSAB) isolates. RESULTS: Recent ventilator-associated pneumonia (VAP) due to CRAB (OR 16.74, 95% CI 3.16-88.79, p = 0.001) and a greater number of intravascular devices (OR 3.93, 95% CI 1.9-13.0, p = 0.025) were independently associated with CRAB bacteremia acquisition. Patients with CRAB bacteremia had a lower severity of illness on admission than those with CSAB. Although, by univariate analysis, patients with CRAB were more likely to have had exposure to colistin, carbapenems and linezolid, multivariate analysis did not revealed any significant association. The mortality was not different between patients with CRAB and CSAB bacteremia (43.3 vs. 46.9%, p = 0.740). Severity of organ failure (OR 1.42, 95% CI 1.20-1.67, p = 0.001), and increased white blood cell (WBC) count (OR 1.09, 95% CI 1.01-1.19, p = 0.036), at bacteremia onset were independently associated with mortality. CONCLUSION: VAP due to CRAB and excess use of intravascular devices are the most important risk factors for CRAB bacteremia in our ICU. Severity of organ failure and WBC count at A. baumannii bacteremia onset are independently associated with mortality.

Risk factors for and influence of bloodstream infections on mortality: a 1-year prospective study in a Greek intensive-care unit.

To determine the incidence, risk factors for, and the influence of bloodstream infections (BSIs) on mortality of patients in intensive-care units (ICUs), prospectively collected data from all patients with a stay in an ICU >48 h, during a 1-year period, were analysed. Of 572 patients, 148 developed a total of 232 BSI episodes (incidence 16.3 episodes/1000 patient-days). Gram-negative organisms with high level of resistance to antibiotics were the most frequently isolated pathogens (157 strains, 67.8%). The severity of illness on admission, as estimated by APACHE II score (OR 1.07, 95% CI 1.04-1.1, P<0.001), the presence of acute respiratory distress syndrome (OR 3.57, 95% CI 1.92-6.64, P<0.001), and a history of diabetes mellitus (OR 2.37, 95% CI 1.36-4.11, P=0.002) were risk factors for the occurrence of BSI whereas the development of an ICU-acquired BSI was an independent risk factor for death (OR 1.76, 95% CI 1.11-2.78, P=0.015). Finally, the severity of organ dysfunction on the day of the first BSI episode, as estimated by SOFA score, and the level of serum albumin, independently affected the outcome (OR 1.44, 95% CI 1.22-1.7, P<0.001 and OR 0.47, 95% CI 0.23-0.97, P=0.04 respectively).

Ongoing epidemic of blaVIM-1-positive Klebsiella pneumoniae in Athens, Greece: a prospective survey.

OBJECTIVES: To determine the current frequency and study the characteristics of VIM-1-producing Klebsiella pneumoniae isolates from bloodstream infections in Greek hospitals. METHODS: All blood isolates of K. pneumoniae were prospectively collected during 2004-06 in three teaching hospitals located in Athens. MICs of antibiotics were determined by the Etest. Extended-spectrum- (ESBL) and metallo-beta-lactamase (MBL) production was examined by clavulanate- and EDTA-based techniques, respectively. Isolates were typed by PFGE of XbaI-digested genomic DNA. Detection of bla(VIM-1) and mapping of the VIM-1-encoding integrons were performed by PCR and sequencing. Beta-lactamase activities were analysed by IEF and imipenem hydrolysis was assessed by spectrophotometry. VIM-1-encoding plasmids were transferred to Escherichia coli by conjugation and transformation and characterized by Inc/rep typing and RFLP. RESULTS: Sixty-seven (37.6%) of 178 K. pneumoniae blood isolates were bla(VIM-1)-positive (VPKP); 77.8% of these were from ICUs. All VPKP isolates were multidrug-resistant. The MICs of carbapenems for VPKP varied from the susceptible range to high-level resistance overlapping with those of MBL-negative isolates. The EDTA-imipenem synergy methods had reduced sensitivity in detecting VPKP isolates when the MICs were in the susceptible range. ESBL production was common among VPKP isolates (n = 45, 67.2%) as indicated by resistance to aztreonam and confirmed by a clavulanate-based double-disc synergy test. The responsible ESBL was always an SHV-5-type enzyme as indicated by IEF. PFGE identified eight clusters (A-H) of VPKP isolates with related (>80%) patterns, as well as four unique types. Both inter-hospital spread of several clones and genotypic similarities among susceptible, ESBL-positive and VPKP isolates were also observed. Location of bla(VIM-1) and expression of VIM-1 were studied in 12 isolates representing the eight PFGE clusters. In all isolates, bla(VIM-1) was part of a class 1 integron that also carried aacA4, dhfrI, aadA and sulI. In eight isolates (clusters C, D, G and H), the bla(VIM-1) integron was located in transferable IncN plasmids. A cluster F isolate carried a VIM-1-encoding, self-transferable plasmid that was not typeable by Inc/rep typing. VIM-1-encodingreplicons were not identified in three isolates (PFGE clusters A, B and E). VPKP isolates exhibited differences in imipenem-hydrolysing activities which, however, were not correlated with the respective carbapenem MICs. CONCLUSIONS: A multiclonal epidemic of bla(VIM-1)-carrying K. pneumoniae is under way in the majorhospitals in Greece. Microorganisms producing both VIM-1 and SHV-5 constitute the prevalent multidrug-resistant population of K. pneumoniae in this setting.

Application of the sequential organ failure assessment (SOFA) score to bacteremic ICU patients.

BACKGROUND: Patients admitted to intensive care units (ICUs) are at a high risk of acquiring blood stream infections. We examined whether SOFA score on ICU admission and on the day of bacteremia can predict the occurrence of bacteremia and the outcome of bacteremic ICU patients. PATIENTS AND METHODS: All patients admitted to a multidisciplinary ICU for more than 48 h from January 1, 2002 to December 31, 2004, were prospectively studied. Demographic, clinical and laboratory data were recorded on admission for all patients and additionally, on the day of the first bacteremic episode for those patients who developed bacteremia. Accordingly, APACHE II and SOFA scores were calculated on the same day. RESULTS: A total of 185 patients developed one or more episodes of bacteremia, giving an incidence of 9.6 per 1,000 ICU days. The ICU mortality rate was 43.9% for bacteremic and 25.8% for the remaining patients (p < 0.001). Admission SOFA score was independently associated with the occurrence of bacteremia (OR = 1.20, 95% CI: 1.11-1.26, p < 0.001). Among bacteremic patients, SOFA score on the day of bacteremia was the only independent prognostic factor for outcome (OR = 1.44, 95% CI: 1.21-1.71, p < 0.001). When all patients were included in the multivariate analysis, admission SOFA (OR = 1.3, CI: 1.16-1.38, p < 0.001), APACHE II (OR = 1.1, CI: 1.02-1.11, p = 0.003) score and the presence of bacteremia (OR = 1.8, CI: 1.1-2.9, p = 0.023) were independently associated with the outcome. CONCLUSION: Admission SOFA score is independently associated with the occurrence of ICU-acquired bacteremia, whereas it is not sufficient to predict the outcome of patients who subsequently will develop this complication. However, SOFA score on the first day of bacteremia is an independent prognostic factor for outcome in these patients.

Detection of enterococcal surface protein gene (esp) and amplified fragment length polymorphism typing of glycopeptide-resistant Enterococcus faecium during its emergence in a Greek intensive care unit.

The emergence of glycopeptide-resistant Enterococcus faecium (GREF) in a Greek intensive care unit was studied by amplified fragment length polymorphism analysis and esp gene detection. Three GREF clones harboring the esp gene were recovered from 17 out of 21 patients, indicating the dissemination of genetically homogenous and virulent strains of GREF.

Bacterial susceptibilities to piperacillin/tazobactam in a tertiary care hospital: 5-year review.

Several factors influence the speed of development of antibacterial resistance, among which is the amount of antibiotic consumption. During the 3-year period 1998-2000, the consumption of piperacillin/tazobactam (pip/tazo) increased by 85% in our hospital. Five years ago we conducted a comparative in vitro study to evaluate susceptibilities of microorganisms to pip/tazo. The objective of the present study was to re-evaluate in vitro susceptibilities to pip/tazo, compared to other beta-lactams, and the potential impact its increased consumption might have on its susceptibility patterns. The study was performed between November 2000 and April 2001. As in 1996, of the beta-lactams studied, pip/tazo and imipenem had the highest susceptibility rates against selected pathogens (>90% susceptibility rates). P. aeruginosa susceptibilities to both imipenem and pip/tazo were high (97% for both). P. aeruginosa susceptibilities to cefepime were lower. Despite its increased use, pip/tazo retained its initially observed high susceptibility rates for the study pathogens.

Extended-spectrum beta-lactamase types in Klebsiella pneumoniae and Escherichia coli in two Greek hospitals.

Seventy-nine Klebsiella pneumoniae and 124 Escherichia coli clinical strains, isolated consecutively during August-October 2001 in two Greek hospitals, were examined for production of extended-spectrum beta-lactamases (ESBLs). Seventy-one (35%) isolates (46 K. pneumoniae and 25 E. coli) were ESBL-positive by phenotypic methods. Isoelectric focusing of beta-lactamases and PCR assays for bla genes showed that SHV-5-type ESBLs were the most frequent (45 isolates, 22%) followed by CTX-M (24 isolates, 12%) and IBC (three isolates, 1.5%). The latter two ESBL types may have been established recently in this setting.

Aspergillus bronchitis causing atelectasis and acute respiratory failure in an immunocompromised patient.

Aspergillus tracheobronchitis is an uncommon clinical form of invasive aspergillosis with fungal infection limited entirely or predominantly to the tracheobronchial tree. We report a case of Aspergillus fumigatus bronchitis, diagnosed by fiberoptic bronchoscopy, with fungal growth completely occluding the left main bronchus leading to lung collapse and acute respiratory failure in a 60-year-old male with erythroleukemia and profound granulocytopenia.

Enterococcal infections in a Greek intensive care unit: a 5-y study.

In this study we determined the incidence, resistance pattern, and mortality rate associated with infection caused by Enterococcus faecalis and Enterococcus faecium among patients in a multidisciplinary intensive care unit (ICU). A total of 111 patients with E. faecalis and 60 with E. faecium infections were identified during a 5-y period (1992-96). We observed an increase in the incidence of enterococcal infections (from 5.46 to 8.46 per 1000 patients-days, p = 0.0112), due mainly to the increased incidence of E. faecium (from 0.45 to 4.06 per 1000 patients-days, p = 0.002). Blood was the most common site of enterococcus isolation. E. faecium was more resistant to antibiotics than E. faecalis, but no vancomycin resistant enterococcus was isolated. Patients with E. faecium infection had a significantly higher mortality than patients with E. faecalis infection (66% vs. 41.5%, p = 0.0035 for infection from any site and 85.7 vs. 47.7%, p = 0.012 for bacteremic patients). r 4n- D I .- .- - .. . .

Diversity of beta-lactam resistance levels among related Klebsiella pneumoniae strains isolated in an intensive care unit.

Seven multiresistant Klebsiella pneumoniae strains isolated in an intensive care unit were studied. Susceptibility to beta-lactams was determined with the E test. Molecular-typing of the isolates was performed by a PCR-based technique (ERIC2-PCR). Sonic cell-extracts were used as beta-lactamase preparations. Beta-lactamase quantities were evaluated measuring nitrocefin hydrolysis. The similarity of the ERIC2-PCR patterns indicated that the seven isolates constituted a single clone. The levels of resistance to oximino-beta-lactams, however, were different. There were indications that the differences in susceptibilities were due, at least partly, to differences in the levels of expression of an extended-spectrum beta-lactamase (most likely SHV-5). Related K. pneumoniae isolates may exhibit different levels of resistance to beta-lactams. Therefore, comparison of resistance phenotypes is of limited usefulness in epidemiological investigations of nosocomial infections caused by resistant K. pneumoniae.

Efficacy and tolerance of roxithromycin versus clarithromycin in the treatment of lower respiratory tract infections.

In an open, randomized, parallel group study, the efficacy and tolerance of roxithromycin 300 mg po od was compared with clarithromycin 500 mg po bd in the treatment of 60 patients with lower respiratory tract infections (LRTI). The two groups were well-matched demographically. Fifty patients (25 per group) were clinically evaluable at the end of the study and a satisfactory response was found in 88% of those given roxithromycin and 80% of those given clarithromycin. All had received treatment for a minimum of 3 days. Only one (3.3%) of 30 patients in the roxithromycin group reported adverse events compared with seven (23.3%) of 30 in the clarithromycin group. Thus both roxithromycin and clarithromycin are effective in the treatment of LRTI but roxithromycin is better tolerated (P < 0.05) with the advantage of a once-daily dose.

Comparative in vitro evaluation of piperacillin/tazobactam in a tertiary care hospital.

Bacterial resistance is usually a serious problem in tertiary care hospitals. The aim of this in vitro study was to evaluate the beta-lactamase inhibitor combination piperacillin/tazobactam in a hospital environment with high bacterial resistance rates and compare it with other beta-lactam agents. Three hundred and sixty-two isolates from various clinical materials were studied during the period March-August 1996. Material for culture was collected from patients of all the wards of our hospital, with the majority being from the Intensive Care Unit (45%). Pathogenic Gram-positive and Gram-negative bacteria with high resistance rates and beta-lactamase production were studied (staphylococci, enterococci, Enterobacteriaceae, Pseudomonas). Significant bacterial resistance rates were identified for ceftazidime (50% for Klebsiellae, 60% for Enterobacter spp, 60% for Proteus spp, 33% for Pseudomonas spp, 75% for Acinetobacter spp) and ciprofloxacin (33% for both Klebsiellae and Enterobacter spp, 67% for Pseudomonas spp, 50% Acinetobacter spp). Fifty percent of Enterococcus isolates were resistance to ciprofloxacin but all of them were susceptible to piperacillin/tazobactam, amoxicillin/clavulanate and imipenem. The antibacterial activity of piperacillin/tazobactam (susceptibility rates 83 to 100% for Enterobacteriaceae, 83% for Pseudomonas spp and 75% for Acinetobacter spp) was higher than that of ceftazidime, piperacillin and ciprofloxacin. Imipenem, being mostly a reserve product, showed higher activity against Acinetobacter, Klebsiella and Enterobacter species.