Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems.

Carbapenemase-producing Klebsiella pneumoniae strains (CP-Kps) are currently among the most important nosocomial pathogens. An observational study was conducted during 2009 to 2010 in two hospitals located in a high-prevalence area (Athens, Greece). The aims were (i) to evaluate the clinical outcome of patients with CP-Kp bloodstream infections (BSIs), (ii) to identify predictors of mortality, and (iii) to evaluate the various antibiotic schemes employed. A total of 205 patients with CP-Kp BSIs were identified: 163 (79.5%) were infected with KPC or KPC and VIM, and 42 were infected with VIM producers. For definitive treatment, 103 patients received combination therapy (two or more active drugs), 72 received monotherapy (one active drug), and 12 received therapy with no active drug. The remaining 18 patients died within 48 h after the onset of bacteremia. The all-cause 28-day mortality was 40%. A significantly higher mortality rate was observed in patients treated with monotherapy than in those treated with combination therapy (44.4% versus 27.2%; P=0.018). The lowest mortality rate (19.3%) was observed in patients treated with carbapenem-containing combinations. In the Cox proportion hazards model, ultimately fatal disease (hazards ratio [HR], 3.25; 95% confidence interval [CI], 1.51 to 7.03; P=0.003), the presence of rapidly fatal underlying diseases (HR, 4.20; 95% CI, 2.19 to 8.08; P<0.001), and septic shock (HR, 2.15; 95% CI, 1.16 to 3.96; P=0.015) were independent predictors of death. Combination therapy was strongly associated with survival (HR of death for monotherapy versus combination, 2.08; 95% CI, 1.23 to 3.51; P=0.006), mostly due to the effectiveness of the carbapenem-containing regimens.

Activity of plazomicin (ACHN-490) against MDR clinical isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. from Athens, Greece.

The in vitro activity of plazomicin was evaluated against 300 multidrug resistant (MDR) (carbapenemase and/or ESBL-producing) isolates from four hospitals in Athens, an area where carbapenemase-producing organisms are endemic. Most of the isolates were also resistant to the legacy aminoglycosides with the MIC50/MIC90 to tobramycin, amikacin and gentamicin being 32/>32, 32/>32 and 4/>8 µg/ml, respectively. ACHN-490 retained activity (MICs ≤ 4 µg/ml) against all isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp. tested with MIC50 and MIC90 of 1 and 2 µg/ml, respectively, irrespective of their MDR phenotype and it represents a promising alternative for the treatment of the most problematic Gram-negative pathogens.

Incidence and risk factors for central vascular catheter-related bloodstream infections in a tertiary care hospital.

This study evaluated the incidence of colonization and infection related to Central Vascular Catheters (CVC) in a tertiary care Greek hospital, as well as risk factors associated with catheter-related bloodstream infection (CRBSI). A total of 340 CVCs, were studied in relation to patient clinical and epidemiological data, CVC characteristics, and microbiological culture results. Risk factors were assessed. Pulsed field gel electrophoresis was used for the investigation of the clonal relationship of the isolates. The incidence for CRBSI and catheter colonization (CC) was 11.47 and 19.49 per 1,000 catheter days, respectively. Risk factors independently associated with CRBSI were use of corticosteroids, diabetes mellitus, solid organ neoplasm, long duration of catheterization, and changing the CVC dressing at intervals of 48 hours or more. Risk factors for CC were diabetes mellitus, hospitalization in ICU, and prolonged hospitalization. The predominant microorganisms isolated from CRBSI episodes were coagulase-negative staphylococci. All patients with CVC require constant infection surveillance and appropriate care by trained medical staff. Use of CVC for the shortest time possible, good hand hygiene and change of CVC dressing at intervals of less than 48 hours are infection prevention practices that need to be followed.

Successful salvage therapy of refractory HIV-related cryptococcal meningitis with the combination of liposomal amphotericin B, voriconazole, and recombinant interferon-γ.

We present 2 cases of HIV-related cryptococcal meningitis, persisting after 3 and 9 months, respectively, of standard treatment. Both patients were treated successfully with a salvage regimen consisting of the combination of liposomal amphotericin B (3 mg/kg), intravenous voriconazole, and subcutaneous recombinant interferon γ-1b (200 µg thrice weekly). Voriconazole was administered at an increased dose (5 mg/kg, twice daily) to overcome interactions with co-administered ritonavir. In both patients, resolution of clinical signs and symptoms, as well as sterilization of cerebrospinal fluid cultures occurred after 10 weeks of salvage therapy. No major side effects were encountered. At the end of treatment, both patients were placed on maintenance therapy with oral fluconazole; no recurrence has been observed after 4 years of follow-up.

Epidemiological characteristics of infections caused by Bacteroides, Prevotella and Fusobacterium species: a prospective observational study.

In order to investigate differences among infections due to Gram-negative anaerobic bacteria (Bacteroides, Prevotella and Fusobacterium spp.), clinical, epidemiological, and microbiological data were collected and evaluated from 206 anaerobic infections. The most frequently isolated species was Bacteroides fragilis. The majority of the cases were intra-abdominal infections (49%) followed by skin and soft tissue infections (24.7%). Logistic regression analysis showed that Bacteroides spp. strains were more often isolated from intra-abdominal infections (p = 0.002), whereas Prevotella spp. were isolated more frequently from cases with shorter duration of hospitalization (p = 0.026), and less frequently from bloodstream infections (p = 0.049). In addition, Bacteroides spp. were associated with coinfection due to Enterobacteriaceae species (p = 0.007), whereas Prevotella spp. were associated with coinfection due to Staphylococcus spp. (p = 0.002). Patients with an infection due to B. fragilis, were more frequently admitted in a general surgical ward (p = 0.017), or have been treated with a 2nd generation cephalosporin before anaerobic infection onset (p = 0.05). Total mortality was 10.9% and was associated with bacteremia (p = 0.026), and hematological (p = 0.028), or solid organ malignancy (p = 0.007). Metronidazole resistance was detected only among Prevotella spp. (16.2%) and B. fragilis group (0.8%) isolates. In conclusion, this study indicated differences between infections due to the most frequently isolated Gram-negative anaerobic species, differences that may affect the design and implementation of empirical antimicrobial chemotherapy guidelines.

Detection of metallo-ß-lactamase genes in clinical specimens by a commercial multiplex PCR system.

hyplex®-MBL ID Multiplex PCR-ELISA, a novel method for identifying metallo-ß-lactamase genes directly in clinical specimens, was evaluated using a consecutive collection of 326 samples from three hospitals in Greece characterized by high prevalence of VIM producers. The method exhibited high sensitivity (98.0%) and specificity (98.6%) and was proven reliable in detecting bla(VIM) genes in blood, urine, pus, and sputum samples that, as confirmed by conventional methods, contained various VIM-producing species. Future multicenter studies should be considered for the thorough evaluation of this method and its potential diagnostic utility.

Lethal Strongyloides stercoralis superinfection in an immunocompromised patient.

In this article, we describe the case of a 49-year-old male gypsy on hemodialysis that was referred to our center due to high fever, breathlessness, and productive cough with bloody sputum. Forty-five days before hospitalization, he was treated for vasculitis with prednisolone and intravenous cyclophosphamide. Soon after admission he was resuscitated and intubated after a cardiac arrest. A large worm load of Strongyloides stercoralis larvae was identified in the sputum. The patient was treated with thiopental 25 mg/kgBW/12 h through a Levine tube and died 24 h later.

Enterobacteriaceae bloodstream infections: presence of integrons, risk factors, and outcome.

A prospective observational study was conducted to identify factors associated with bloodstream infections (BSIs) caused by integron-carrying Enterobacteriaceae and to evaluate the clinical significance of integron carriage. Consecutive patients with Enterobacteriaceae BSIs were identified and followed up until discharge or death. Identification of blood isolates and susceptibility testing were performed by the Wider I automated system. int-1-specific PCR, conserved-segment PCR, and DNA sequencing were used to determine the presence, length, and content of integrons. The relatedness among the isolates was examined by pulsed-field gel electrophoresis. Two hundred fifty episodes of Enterobacteriaceae BSI occurred in 233 patients; 109 (43.6%) were nosocomial, 82 (32.8%) were community acquired, and 59 (23.6%) were health care associated. Integrons were detected in 11 (13.4%) community-acquired, 24 (40.7%) health care-associated, and 46 (42.2%) nosocomial isolates. Integron-carrying organisms were more likely to exhibit resistance to three or more classes of antimicrobials (odds ratio [OR], 9.84; 95% confidence interval [95% CI], 5.31 to 18.23; P < 0.001) or to produce extended-spectrum beta-lactamases (OR, 5.75; 95% CI, 2.38 to 13.89; P < 0.001) or a VIM-type metallo-beta-lactamase (P, 0.003). Inter- or intraspecies integron transfer and cross-transmission of integron-carrying clones were observed. Use of cotrimoxazole (OR, 4.77; 95% CI, 1.81 to 12.54; P < 0.001) and a nosocomial or other health care setting (OR, 3.07; 95% CI, 1.30 to 7.22; P, 0.01) were independently associated with BSIs caused by integron-carrying Enterobacteriaceae. Patients with a nonurinary source of bacteremia (OR, 9.46; 95% CI, 2.77 to 32.32; P < 0.001) and a Pitt bacteremia score of > or =4 (OR, 23.36; 95% CI, 7.97 to 68.44; P < 0.001) had a significantly higher 14-day mortality rate, whereas integron carriage did not affect clinical outcomes. These findings may have implications affecting antibiotic policies and infection control measures.

Differences in the evolution of imipenem susceptibility among Klebsiella pneumoniae and Escherichia coli isolates during a 6-year period in a tertiary care hospital.

The evolution of imipenem disk-diffusion susceptibility results of 2652 strains of Klebsiella pneumoniae and 7596 Escherichia coli isolated during the period 2000-2005 were analysed. Screening for production of metallo-beta-lactamases was performed using the EDTA-synergy method. The percentage rate of K. pneumoniae isolates having a zone diameter < or =25 mm increased from 20% in 2000 to 41% in 2005, whereas the respective rate of isolates having a zone diameter > or =30 mm decreased from 48 to 23%. These changes were more evident during 2000-2002, followed in 2003 by the isolation of the first imipenem-resistant strains. Regarding E. coli, a similar decrease was observed (the rates of isolates having a zone diameter < or =25 mm and > or =30 mm changed from 7% and 68% in 2000, to 32% and 36% in 2005, respectively) following the respective changes of K. pneumoniae. A total of 20 K. pneumoniae strains, but no E. coli, were confirmed as metallo-beta-lactamase producers. In conclusion, a decrease of the imipenem susceptibility prior to the isolation of the first resistant strains in a tertiary care hospital was detected, as well as differences in this decrease between the two species. These findings indicate that monitoring of the evolution of imipenem susceptibility in real-time may help in unveiling forthcoming resistance and in implementing the appropriate diagnostic techniques.

Septic arthritis due to Roseomonas mucosa in a rheumatoid arthritis patient receiving infliximab therapy.

We report a case of septic arthritis due to Roseomonas mucosa in a rheumatoid arthritis patient receiving infliximab therapy. This is the first report of septic arthritis due to R. mucosa, and infliximab therapy might be a predisposing factor because this infection was never reported in the pre-anti-tumor necrosis factor alpha therapy period.

Campylobacter fetus bacteraemia in a healthy individual: clinical and therapeutical implications.

Campylobacter species are well-recognized common causes of gastrointestinal infections. While Campylobacter jejuni is probably the most common Campylobacter isolated in humans, Campylobacter fetus is rather infrequent and mostly related with bacteraemia. Even on such occasions, it seems that immunocompetent individuals are spared. We report a case of C. fetus bacteraemia in a healthy-except for impaired fasting glucose (IFG) levels-farmer, presenting as an acute febrile syndrome and treated successfully as brucellosis.

Changes in the epidemiology of methicillin-resistant Staphylococcus aureus in a Greek tertiary care hospital, over an 8-year-period.

A total of 1019 non-replicate, consecutively isolated methicillin-resistant Staphylococcus aureus (MRSA) strains were collected from in-patients of a tertiary care general hospital in Athens, Greece, during the period 1994-2001. The susceptibility, resistance phenotypes and the dissemination of these isolates among hospital wards were studied. Total MRSA and gentamicin-resistant MRSA, as a proportion of the S. aureus isolates, increased from 33 and 9% in 1994 to 50.1 and 33.3% in 2001, respectively. Three main multi-resistant phenotypes predominated, representing 50.9% of the total MRSA isolates in 2001. MRSA strains susceptible to all antibiotics tested decreased to 1.9% in 1997 and again increased to 13.5% in 2001. A gradual decrease in the susceptibility of vancomycin during the 8-year-period was detected, but no vancomycin resistant S. aureus strains were isolated.