Prevention of hospital infections by intervention and training (PROHIBIT): results of a pan-European cluster-randomized multicentre study to reduce central venous catheter-related bloodstream infections.

PURPOSE: To test the effectiveness of a central venous catheter (CVC) insertion strategy and a hand hygiene (HH) improvement strategy to prevent central venous catheter-related bloodstream infections (CRBSI) in European intensive care units (ICUs), measuring both process and outcome indicators. METHODS: Adult ICUs from 14 hospitals in 11 European countries participated in this stepped-wedge cluster randomised controlled multicentre intervention study. After a 6 month baseline, three hospitals were randomised to one of three interventions every quarter: (1) CVC insertion strategy (CVCi); (2) HH promotion strategy (HHi); and (3) both interventions combined (COMBi). Primary outcome was prospective CRBSI incidence density. Secondary outcomes were a CVC insertion score and HH compliance. RESULTS: Overall 25,348 patients with 35,831 CVCs were included. CRBSI incidence density decreased from 2.4/1000 CVC-days at baseline to 0.9/1000 (p < 0.0001). When adjusted for patient and CVC characteristics all three interventions significantly reduced CRBSI incidence density. When additionally adjusted for the baseline decreasing trend, the HHi and COMBi arms were still effective. CVC insertion scores and HH compliance increased significantly with all three interventions. CONCLUSIONS: This study demonstrates that multimodal prevention strategies aiming at improving CVC insertion practice and HH reduce CRBSI in diverse European ICUs. Compliance explained CRBSI reduction and future quality improvement studies should encourage measuring process indicators.

Diagnosis of Upper and Lower Respiratory Tract Bacterial Infections with the Use of Multiplex PCR Assays.

The investigation of respiratory infections by molecular techniques provides important information about the epidemiology of respiratory disease, especially during the post-vaccination era. The objective of the present study was the detection of bacterial pathogens directly in clinical samples from patients with upper and lower respiratory tract infections using multiplex polymerase chain reaction (PCR) assays developed in our laboratory. Clinical samples taken over a three-year period (2007-2009) and obtained from 349 patients (adults (n = 66); children (n = 283)) with signs and symptoms of certain upper or lower respiratory tract infections, consisted of: bronchoalveolar lavages (BAL, n = 83), pleural fluids (n = 29), and middle-ear aspirates (n = 237). Overall, 212 samples (61%) were confirmed by culture and/or PCR. Among the positive samples, Streptococcus pneumoniae (mainly serotype 3) was predominant (104/212; 49.0%), followed by non-typable Haemophilus influenzae (NTHi) 59/212; 27.8%) and Streptococcus pyogenes (47/212; 22%). Haemophilus influenzae type b was detected in only three samples. The underlying microbiology of respiratory infections is gradually changing in response to various selective pressures, such as vaccine use and antibiotic consumption. The application of multiplex PCR (mPCR) assays is particularly useful since it successfully identified the microorganisms implicated in acute otitis media or lower respiratory tract infections in nearly 75% of patients with a positive result compared to conventional cultures. Non-culture identification of the implicated pneumococcal serotypes is also an important issue for monitoring pneumococcal infections in the era of conjugate pneumococcal vaccines.

Clinical impact of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay related to methicillin-resistant Staphylococcus aureus bloodstream infections.

Antimicrobial resistance is threatening the successful management of nosocomial infections worldwide. Despite the therapeutic limitations imposed by methicillin-resistant Staphylococcus aureus (MRSA), its clinical impact is still debated. The objective of this study was to estimate the excess mortality and length of hospital stay (LOS) associated with MRSA bloodstream infections (BSI) in European hospitals. Between July 2007 and June 2008, a multicenter, prospective, parallel matched-cohort study was carried out in 13 tertiary care hospitals in as many European countries. Cohort I consisted of patients with MRSA BSI and cohort II of patients with methicillin-susceptible S. aureus (MSSA) BSI. The patients in both cohorts were matched for LOS prior to the onset of BSI with patients free of the respective BSI. Cohort I consisted of 248 MRSA patients and 453 controls and cohort II of 618 MSSA patients and 1,170 controls. Compared to the controls, MRSA patients had higher 30-day mortality (adjusted odds ratio [aOR] = 4.4) and higher hospital mortality (adjusted hazard ratio [aHR] = 3.5). Their excess LOS was 9.2 days. MSSA patients also had higher 30-day (aOR = 2.4) and hospital (aHR = 3.1) mortality and an excess LOS of 8.6 days. When the outcomes from the two cohorts were compared, an effect attributable to methicillin resistance was found for 30-day mortality (OR = 1.8; P = 0.04), but not for hospital mortality (HR = 1.1; P = 0.63) or LOS (difference = 0.6 days; P = 0.96). Irrespective of methicillin susceptibility, S. aureus BSI has a significant impact on morbidity and mortality. In addition, MRSA BSI leads to a fatal outcome more frequently than MSSA BSI. Infection control efforts in hospitals should aim to contain infections caused by both resistant and susceptible S. aureus.

Epidemiology, risk factors for and outcome of candidaemia among non-neutropenic patients in a Greek intensive care unit.

To determine the epidemiology, risk factors for and outcome of candidaemia in critically ill patients, a matched case-control study was performed in a 25-bed intensive care unit (ICU) from August 2004 to January 2006. Candidaemia occurred in 33 patients; each patient was matched to four controls according to admission illness severity, diagnostic category and length of ICU stay. Candida non-albicans species predominated (67.7%). The presence of acute respiratory distress syndrome (ARDS) was the only independent risk factor for candidaemia development (OR, 2.93; 95% CI 1.09-7.81, P = 0.032). Mortality was 60.6% among patients with candidaemia and 22% among controls (P < 0.001). The presence of candidaemia (OR, 9.37; 95% CI 3.48-25.26, P < 0.001) and the illness severity on admission (acute physiologic and chronic health evaluation II score, OR, 1.17; 95% CI 1.12-1.24, P < 0.001) were independently associated with mortality. Among candidaemic patients, risk factors for mortality were the severity of organ dysfunction (sequential organ failure assessment score, OR, 1.57; 95% CI 1.00-2.46, P = 0.05) and a low serum albumin level (OR, 0.74; 95% CI 0.59-0.94, P = 0.012) both of them occurred on candidaemia onset. We conclude that in critically ill patients matched for illness severity and length of ICU stay, the only independent risk factor for candidaemia was the presence of ARDS. Mortality was independently associated with acquisition of candidaemia and with the illness severity at candidaemia onset.

Identification of staphylococci by Phoenix: validation of a new protocol and comparison with Vitek 2.

Because of their frequent isolation in the routine laboratory and their increasing clinical significance, fast and accurate species identification of staphylococci may be required; this can only be achieved by automated systems. A total of 147 clinical isolates (52 Staphylococcus aureus, 50 Staphylococcus epidermidis, and 45 other coagulase-negative staphylococci [CoNS]) were first identified by molecular methodology and then comparatively tested by Vitek 2 (new colorimetric identification card) and Phoenix using the novel 0.25 McFarland and the standard 0.50 McFarland inoculum protocols. All S. aureus isolates were accurately identified. Vitek 2 identified correctly all S. epidermidis and 93.3% of the other CoNS, whereas the respective rates were 86% and 82.2% for Phoenix's standard and 92% and 82.2% for the novel protocol. It appears that both systems provide excellent identification of S. aureus, but Vitek 2 recognizes CoNS species more accurately than Phoenix. The 0.25 McFarland protocol does not improve system performance.

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.

Poststernotomy sternal osteomyelitis and mediastinitis by Trichosporon asahii: a rare occurrence with a grave prognosis.

Post-sternotomy infectious complications, including superficial and deep wound infections, sternal osteomyelitis and mediastinitis, are rarely caused by fungi. Trichosporon asahii is the main Trichosporon species that causes systemic infection in humans. Most cases involved neutropenic patients with hematologic malignancies. We report a unique case of a non-cancer, non-neutropenic but severely ill patient who developed an ultimately lethal T. asahii infection after sternotomy. We speculate that our patient had been colonized with the fungus and his surgical site infection may have been related to his emergency revascularization surgery. Therapy with liposomal amphotericin failed to sterilize the bloodstream despite in vitro susceptibility results. The addition of voriconazole helped sterilizing the bloodstream without changing the outcome. Physicians must be aware of the continuously expanding spectrum of infections with this emerging difficult-to-treat fungal pathogen.

An outbreak of hemodialysis catheter-related bacteremia with sepsis caused by Streptococcus agalactiae in a hemodialysis unit.

BACKGROUND: Rates of invasive group B Streptococcus (GBS; Streptococcus agalactiae) disease in adults are on the rise. Invasive GBS disease can be community- or healthcare-associated. We report an outbreak of GBS catheter-related bacteremia in a hemodialysis (HD) unit. MATERIALS AND METHODS: Two patients undergoing HD at the same outpatient HD unit were admitted on the same day (within a few hours of each other) with catheter-related GBS bacteremia. A retrospective study was undertaken at the HD unit to address risk factors for febrile illness on the last HD session day. A detailed questionnaire was completed by all HD patients treated on the same day as the two GBS patients and by all members of the nursing and medical staff. Medical and nursing records of the HD unit were reviewed, as well as infection control and catheter care practices. Patients and staff members submitted swabs for culture. RESULTS: No rectal or vaginal culture of any HD patient or staff member was positive for GBS. The development of recent febrile disease was significantly associated with the presence of a hemodialysis catheter (p=0.028) and care for more than 30min by a specific nurse during the last two HD sessions (p=0.007). CONCLUSIONS: We speculate that the GBS strain was transmitted from one patient to the other through the hands of medical personnel. No such outbreak has ever been reported in HD patients. The importance of strict infection control practices in HD units and the avoidance of catheters for long-term HD should be emphasized.

Community-acquired methicillin-resistant Staphylococcus aureus as a cause of rapidly progressing pyelonephritis with pyonephrosis, necessitating emergent nephrectomy.

In this article, we describe the first, to our knowledge, reported case of severe bacteremic upper urinary tract infection with pyonephrosis-in the context of prior chronic urinary tract disease-caused by community-acquired methicillin-resistant Staphylococcus aureus (MRSA). The patient presented with fever and constitutional symptoms, and computed tomography revealed extensive renal parenchymal infection along with a staghorn calculus and dilatation of the pyelocalyceal system. His clinical condition rapidly deteriorated, and he developed uncontrollable sepsis, necessitating an emergent nephrectomy. Significant pyonephrosis was noted during surgery. Blood cultures yielded MRSA, and molecular analysis (by polymerase chain reaction) of the MRSA strains from blood and wound fluid showed that they were Panton-Valentine leukocidin positive and they also possessed SCCmecA type IV. Postoperatively, the patient was treated with intravenous vancomycin for 3 weeks and had a favorable outcome.

Primary sternal osteomyelitis caused by Nocardia nova: case report and literature review.

A 51 year old woman without significant past medical history or risk factors for Nocardia infection developed primary Nocardia nova sternal osteomyelitis with mediastinal abscess, diagnosed with open biopsy. She required prolonged antibiotic therapy and had a favorable outcome. Primary sternal osteomyelitis develops in the absence of a contiguous focus of infection, as opposed to secondary sternal osteomyelitis, which is usually a complication of sternotomy. Staphylococcus aureus probably still is the most common cause of both forms of sternal osteomyelitis. Nocardia species invade humans usually through the respiratory tract and can cause a variety of localized infections through the hematogenous route. Pulmonary involvement may or may not coexist. Immunosuppressed patients are more prone to infection by Nocardia species, although cases involving seemingly immunocompetent patients are not rare. This is the first reported case in the English literature of primary sternal osteomyelitis due to Nocardia nova or any other Nocardia species.

Primary sternal osteomyelitis caused by Nocardia nova: case report and literature review

A 51 year old woman without significant past medical history or risk factors for Nocardia infection developed primary Nocardia nova sternal osteomyelitis with mediastinal abscess, diagnosed with open biopsy. She required prolonged antibiotic therapy and had a favorable outcome. Primary sternal osteomyelitis develops in the absence of a contiguous focus of infection, as opposed to secondary sternal osteomyelitis, which is usually a complication of sternotomy. Staphylococcus aureus probably still is the most common cause of both forms of sternal osteomyelitis. Nocardia species invade humans usually through the respiratory tract and can cause a variety of localized infections through the hematogenous route. Pulmonary involvement may or may not coexist. Immunosuppressed patients are more prone to infection by Nocardia species, although cases involving seemingly immunocompetent patients are not rare. This is the first reported case in the English literature of primary sternal osteomyelitis due to Nocardia nova or any other Nocardia species.

Fatal post-traumatic zygomycosis in an immunocompetent young patient.

Zygomycosis, a relatively uncommon infection, usually occurs among immunocompromised individuals. It has been reported only rarely in trauma patients. A fatal case is reported of pulmonary and rapidly progressive cutaneous zygomycosis in a young, otherwise healthy farmer, with multiple bone fractures, wounds and soft tissue injuries after an accident with an agricultural machine in the field. Rhizopus spp. was isolated from both cultures of bronchial washings and wound samples. The diagnosis was confirmed by histopathological examination of tissue specimens from a large wound. Despite systemic antifungal therapy and surgical debridement, the patient's condition deteriorated and he died from refractory septic shock.

Prolonged use of carbapenems and colistin predisposes to ventilator-associated pneumonia by pandrug-resistant Pseudomonas aeruginosa.

OBJECTIVE: We present our experience with five cases of pandrug-resistant Pseudomonas aeruginosa ventilator-associated pneumonia (VAP) and analysis of risk factors. DESIGN AND SETTING: Case-control study in a 15-bed intensive care unit (ICU). PATIENTS AND PARTICIPANTS: The study included 5 cases and 20 controls. Each case patient was matched to four contemporary controls according to gender, prior hospital admissions, hospitalization duration, ICU admission cause, Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Function Assessment (SOFA) scores on ICU admission, and length of ICU stay, and mechanical ventilation duration until first VAP episode by a multidrug-resistant bacterium. MEASUREMENTS AND RESULTS: Recorded variables included age, gender, daily APACHE II and SOFA scores, patient medication, treatment interventions, positive cultures and corresponding antibiograms, occurrence of infection, sepsis, and septic shock, other ICU-associated morbidity, length of ICU stay and mechanical ventilation, and patient outcome. Healthcare worker and environmental cultures, and a hand-disinfection survey were performed. Pandrug-resistant P. aeruginosa isolates belonged to the same genotype and were bla (VIM-1)-like gene positive. The outbreak resolved following reinforcement of infection-control measures (September 27). The sole independent predictor for pandrug-resistant P. aeruginosa VAP was combined use of carbapenem for more than 20 days and colistin use for and more than 13 days (odds ratio 76.0; 95% confidence interval 3.7-1487.6). An additional risk factor was more than 78 open suctioning procedures during 6-26 September (odds ratio 16.0; 95% confidence interval 1.4-185.4). CONCLUSIONS: Prolonged carbapenem-colistin use predisposes to VAP by pandrug-resistant P. aeruginosa. Cross-transmission may be facilitated by open suctioning.

Molecular investigation of an outbreak of multidrug-resistant Acinetobacter baumannii, with characterisation of class 1 integrons.

We investigated a multidrug-resistant Acinetobacter baumannii outbreak in the Intensive Care Unit (ICU) of a tertiary care hospital in Greece over a 3-month period. Molecular typing of the outbreak isolates from 31 patients revealed that two distinct genotypes were involved. Nine isolates, belonging to both genotypes, were resistant to carbapenems. Samples from the ICU environment and from the hands of personnel were collected to identify possible contamination. Class 1 integrons of 3.1, 2.5 and 2.2 kb were amplified from the clinical and environmental isolates. The 3.1 kb integron carrying five gene cassettes was found for the first time in A. baumannii. The outbreak ceased after implementation of hygienic measures in the ICU, including complete cleaning and disinfection.

In vitro biocompatibility between mitomycin-C (MMC) and bacillus Calmette-Guerin (BCG).

BACKGROUND: Mitomycin-C (MMC) and bacillus Calmette-Guerin (BCG) intravesical instillations are widely and effectively used as adjuvant treatment for superficial bladder cancer. In an attempt to improve the efficacy of intravesical therapy, MMC and BCG have also been used in a sequential or an alternating mode. The aim of this study was to assess the in vitro biocompatibility between these agents. MATERIALS AND METHODS: The effect of MMC on BCG clumping tendency was assessed by estimating the number of colony forming units (CFU) of BCG in suspension, during incubation at 37 degrees C for 3 h, with repeated recordings of the suspension optical density (OD). Preparations containing either BCG plus MMC or BCG plus an equivalent amount of sterile water were cultivated using the non-radiometric system BACTEC MGIT 960. The final concentrations of the agents, following transfer of the preparations into the tubes of the system, were 1.25 mg/ml for BCG and 1 mg/ml for MMC. During the cultivation process, the tubes of the system were automatically checked every 60 min for fluorescence emission, which is an indication of mycobacteria growth. A comparative cultivation of the same preparations on Lowenstein-Jensen solid medium was also performed. RESULTS: The OD of the BCG preparation remained almost unaffected for 3 h and was minimally altered by inclusion of MMC. After 34-38 h of cultivation in the BACTEC MGIT 960 system, all 7 cultures of the BCG+sterile water preparations became positive. In contrast, no BCG+MMC specimen became positive after an incubation period of 42 days. Following re-cultivation of the 7 negative BCG+MMC specimens, 6 remained negative, whereas 1 specimen became positive after an incubation period of 22 days. On Löwenstein-Jensen medium, growth of mycobacteria was noted only in the BCG+sterile water specimens and not in the BCG+MMC specimens. CONCLUSION: The results of this study indicate that, although MMC has no apparent effect on BCG tendency to form clumps in suspension, it may inhibit its growth in vitro. However, this does not necessarily compromise BCG anti-tumour activity. As the in vivo interaction of the drugs may be different, the efficacy of the combined BCG+MMC treatment should be defined in clinical trials.

Stenotrophomonas maltophilia meningitis, bacteremia and respiratory infection.

Stenotrophomonas maltophilia is an increasingly recognized cause of nosocomial infection of special interest because of its resistance to multiple antimicrobial agents. We report a case of generalized infection by S. maltophilia, including meningitis, bacteremia and respiratory tract infection, in a patient who had undergone multiple neurosurgical procedures and who was treated with trimethoprim-sulphamethoxazole.