Increasing numbers of admissions for sepsis impose a heavy burden on health care systems worldwide, while novel therapies have proven both expensive and ineffective. We explored the long-term ...mortality and hospitalization costs after adjunctive therapy with intravenous clarithromycin in ventilator-associated pneumonia (VAP). Two hundred patients with sepsis and VAP were enrolled in a published randomized clinical trial; 100 were allocated to blind treatment with a placebo and another 100 to clarithromycin at 1 g daily for three consecutive days. Long-term mortality was recorded. The hospitalization cost was calculated by direct quantitation of imaging tests, medical interventions, laboratory tests, nonantibiotic drugs and antibiotics, intravenous fluids, and parenteral and enteral nutrition. Quantities were priced by the respective prices defined by the Greek government in 2002. The primary endpoint was 90-day mortality; cumulative hospitalization cost was the secondary endpoint. All-cause mortality rates on day 90 were 60% in the placebo arm and 43% in the clarithromycin arm (P = 0.023); 141 patients were alive on day 28, and mortality rates between days 29 and 90 were 44.4% and 17.4%, respectively (P = 0.001). The mean cumulative costs on day 25 in the placebo group and in the clarithromycin group were €14,701.10 and €13,100.50 per patient staying alive, respectively (P = 0.048). Respective values on day 45 were €26,249.50 and €19,303.10 per patient staying alive (P = 0.011); this was associated with the savings from drugs other than antimicrobials. It is concluded that intravenous clarithromycin for three consecutive days as an adjunctive treatment in VAP and sepsis offers long-term survival benefit along with a considerable reduction in the hospitalization cost. (This study has been registered at ClinicalTrials.gov under registration no. NCT00297674.).
The serine protease activated protein C (APC) possesses prominent anticoagulant and anti-inflammatory actions. In this study, we investigated the effect of inhaled recombinant human (rh) APC in a ...murine lung injury model. Animals inhaled 10 mg of
Pseudomonas lipopolysaccharide (LPS) in 3 mL normal saline (NS); 30 min prior to LPS, mice were pretreated with inhaled rhAPC (4 mg/3 mL NS; APC
+
LPS group) or NS (LPS group). A control animal group inhaled vehicle (NS) twice. 24 h later, total cells and cell-types, protein content, and the cytokines tumor necrosis factor-α, interleukin (IL)-6, macrophage inflammatory protein-1α, and mouse keratinocyte-derived chemokine (a homolog of human IL-8) were estimated in bronchoalveolar lavage fluid (BALF). Lung pathology given as total histology score (THS), wet/dry lung weight ratios, and lung vascular cell adhesion molecule (VCAM)-1 expression were additionally assessed. rhAPC inhalation attenuated the aerosolized LPS-induced increases of: total cells, neutrophils and macrophages in BALF, lung tissue VCAM-1 protein levels, and THS. Total protein levels and cytokines in BALF, and wet/dry weight ratios were increased in the LPS group, but rhAPC pretreatment did not significantly alter the LPS-induced responses. In conclusion, in this murine septic model of lung injury, inhaled rhAPC appears to attenuate lung inflammation, without reversing the observed increases in lung permeability and BALF cytokines. This effect may be associated with leukocyte trafficking modifications, related, at least in part, to VCAM-1 reduction.
Background. We describe the emergence and spread of Klebsiella pneumoniae carbapenemase 2 (KPC-2)–producing K. pneumoniae at a Greek University hospital. Methods. Isolates with a carbapenem minimum ...inhibitory concentration >1 µg/mL and a negative EDTA-imipenem disk synergy test result were submitted to boronic acid disk test and to polymerase chain reaction (PCR) for KPC gene and sequencing. Records from patients who had KPC-2–producing K. pneumoniae isolated were retrospectively reviewed. Clinical isolates were submitted to molecular typing using pulsed-field gel electrophoresis, and the β-lactamase content was studied using isoelectric focusing and PCR. Results. From January 2007 through December 2008, 50 patients (34 in the intensive care unit ICU) were colonized (n=32) or infected (n=18) by KPC-2–producing K. pneumoniae. Increasing prevalence of KPC-2–producing K. pneumoniae coincided with decreasing prevalence of metallo-β lactamase–producing isolates in our ICU. Multidrug resistance characterized the studied isolates, with colistin, gentamicin, and fosfomycin being the most active agents. Besides KPC-2, clinical isolates encoded TEM-1-like, SHV-11, SHV-12, CTX-M–15, and LEN-19 enzymes. Four different clonal types were detected; the predominant one comprised 41 single patient isolates (82%). Sporadic multiclonal cases of KPC-2–producing K. pneumoniae infection were identified from September 2007 through May 2008. The outbreak strain was introduced in February 2008 and disseminated rapidly by cross-transmission; 38 patients (76%) were identified after August 2008. Fourteen cases of bacteremia, 2 surgical site infections, 2 lower respiratory tract infections (1 bacteremic), and 1 urinary tract infection were identified. Most patients received a colistin-containing combination treatment. Crude mortality was 58.8% among ICU patients and 37.5% among non-ICU patients, but attributable mortality was 22.2% and 33.3%, respectively. Conclusions. The emergence of KPC-2–producing K. pneumoniae in Greek hospitals creates an important challenge for clinicians and hospital epidemiologists, because it is added to the already high burden of antimicrobial resistance.
Objectives Infections due to multidrug-resistant (MDR) Gram-negative pathogens in the ICU have prompted the use of colistin, an antibiotic forgotten for decades. The aim of this retrospective ...observational study was to record and present the emergence of colistin-resistant Klebsiella pneumoniae (CRKB) in a Greek ICU. Methods In a new university tertiary hospital, the first patients admitted in the ICU were already colonized or infected with MDR pathogens, and this led to frequent colistin use as part of empirical or microbiologically documented therapy. Colistin resistance was defined as MIC >4 mg/L by the Etest method. All CRKB isolated in surveillance cultures or clinical specimens in the ICU during the period 2004–5 were recorded along with patients' characteristics. Results Eighteen CRKB were isolated from 13 patients over a 16 month period, representing either colonizing or infective isolates. Patients' mean age was 70 years, with a mean APACHE II score at admission of 22. They all had a long hospitalization (median 69 days) and a long administration of colistin (median 27 days). Colistin-resistant isolates were implicated as pathogens in two bacteraemias, a ventilator-associated pneumonia and two soft tissue infections. Repetitive extragenic palindromic PCR identified six distinct clones, and horizontal transmission was also documented. Conclusions Selective pressure due to extensive or inadequate colistin use may lead to the emergence of colistin resistance among K. pneumoniae isolates, jeopardizing treatment options in the ICU, potentially increasing morbidity and mortality of critically ill patients and necessitating prudent use of colistin.
OBJECTIVE To evaluate the efficacy of copper-coating in reducing environmental colonization in an intensive-care unit (ICU) with multidrug-resistant-organism (MDRO) endemicity DESIGN Interventional, ...comparative crossover trial SETTING The general ICU of Attikon University hospital in Athens, Greece PATIENTS Those admitted to ICU compartments A and B during the study period METHODS Before any intervention (phase 1), the optimum sampling method using 2 nylon swabs was validated. In phase 2, 6 copper-coated beds (ie, with coated upper, lower, and side rails) and accessories (ie, coated side table, intravenous i.v. pole stands, side-cart handles, and manual antiseptic dispenser cover) were introduced as follows: During phase 2a (September 2011 to February 2012), coated items were placed next to noncoated ones (controls) in both compartments A and B; during phase 2b (May 2012 to January 2013), all copper-coated items were placed in compartment A, and all noncoated ones (controls) in compartment B. Patients were randomly assigned to available beds. Environmental samples were cultured quantitatively for clinically important bacteria. Clinical and demographic data were collected from medical records. RESULTS Copper coating significantly reduced the percentage of colonized surfaces (55.6% vs 72.5%; P<.0001), the percentage of surfaces colonized by MDR gram-negative bacteria (13.8% vs 22.7%; P=.003) or by enterococci (4% vs 17%; P=.014), the total bioburden (2,858 vs 7,631 cfu/100 cm2; P=.008), and the bioburden of gram-negative isolates, specifically (261 vs 1,266 cfu/100 cm2; P=.049). This effect was more pronounced when the ratio of coated surfaces around the patient was increased (phase 2b). CONCLUSIONS Copper-coated items in an ICU setting with endemic high antimicrobial resistance reduced environmental colonization by MDROs. Infect Control Hosp Epidemiol 2017;38:765-771.
Background. Because clarithromycin provided beneficiary nonantibiotic effects in experimental studies, its efficacy was tested in patients with sepsis and ventilator-associated pneumonia (VAP). ...Methods. Two hundred patients with sepsis and VAP were enrolled in a double-blind, randomized, multicenter trial from June 2004 until November 2005. Clarithromycin (1 g) was administered intravenously once daily for 3 consecutive days in 100 patients; another 100 patients were treated with placebo. Main outcomes were resolution of VAP, duration of mechanical ventilation, and sepsis-related mortality within 28 days. Results. The groups were well matched with regard to demographic characteristics, disease severity, pathogens, and adequacy of the administered antimicrobials. Analysis comprising 141 patients who survived revealed that the median time for resolution of VAP was 15.5 days and 10.0 days among placebo- and clarithromycin-treated patients, respectively (P=.011); median times for weaning from mechanical ventilation were 22.5 days and 16.0 days, respectively (P=.049). Analysis comprising all enrolled patients showed a more rapid decrease of the clinical pulmonary infection score and a delay for advent of multiple organ dysfunction in clarithromycin-treated patients, compared with those of placebo-treated patients (P=.047). Among the 45 patients who died of sepsis, time to death was significantly prolonged in clarithromycin-treated compared with placebo-treated patients (P=.004). Serious adverse events were observed in 0% and 3% of placebo- and clarithromycin-treated patients, respectively (P=.25). Conclusions. Clarithromycin accelerated the resolution of VAP and weaning from mechanical ventilation in surviving patients and delayed death in those who died of sepsis. The mortality rate at day 28 was not altered. Results are encouraging and render new perspectives on the management of sepsis and VAP.
Background
A previous randomized study showed that clarithromycin decreases the risk of death due to ventilator-associated pneumonia and shortens the time until infection resolution. The efficacy of ...clarithromycin was tested in a larger population with sepsis.
Methods
Six hundred patients with systemic inflammatory response syndrome due to acute pyelonephritis, acute intra-abdominal infections or primary Gram-negative bacteraemia were enrolled in a double-blind, randomized, multicentre trial. Clarithromycin (1 g) was administered intravenously once daily for 4 days consecutively in 302 patients; another 298 patients were treated with placebo. Mortality was the primary outcome; resolution of infection and hospitalization costs were the secondary outcomes.
Results
The groups were well matched for demographics, disease severity, microbiology and appropriateness of the administered antimicrobials. Overall 28 day mortality was 17.1% (51 deaths) in the placebo arm and 18.5% (56 deaths) in the clarithromycin arm (P = 0.671). Nineteen out of 26 placebo-treated patients with septic shock and multiple organ dysfunctions died (73.1%) compared with 15 out of 28 clarithromycin-treated patients (53.6%, P = 0.020). The median time until resolution of infection was 5 days in both arms. In the subgroup with severe sepsis/shock, this was 10 days in the placebo arm and 6 days in the clarithromycin arm (P = 0.037). The cost of hospitalization was lower after treatment with clarithromycin (P = 0.044). Serious adverse events were observed in 1.3% and 0.7% of placebo- and clarithromycin-treated patients, respectively (P = 0.502).
Conclusions
Intravenous clarithromycin did not affect overall mortality; however, administration shortened the time to resolution of infection and decreased the hospitalization costs.
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