The revival of fosfomycin.

Fosfomycin, originally named phosphonomycin, was discovered in Spain in 1969. There are three forms of fosfomycin: fosfomycin tromethamine (a soluble salt) and fosfomycin calcium for oral use, and fosfomycin disodium for intravenous use. Fosfomycin is a bactericidal antibiotic that interferes with cell wall synthesis in both Gram-positive and Gram-negative bacteria by inhibiting the initial step involving phosphoenolpyruvate synthetase. It has a broad spectrum of activity against a wide range of Gram-positive and Gram-negative bacteria. It is highly active against Gram-positive pathogens such as Staphylococcus aureus and Enterococcus, and against Gram-negative bacteria such as Pseudomonas aeruginosa and Klebsiella pneumoniae. Its unique mechanism of action may provide a synergistic effect to other classes of antibiotics including beta-lactams, aminoglycosides, and fluoroquinolones. Oral fosfomycin is mainly used in the treatment of urinary tract infections, particularly those caused by Escherichia coli and Enterococcus faecalis. Intravenous fosfomycin has been administered in combination with other antibiotics for the treatment of nosocomial infections due to multidrug-resistant (MDR) Gram-positive and Gram-negative bacteria. Fosfomycin has good distribution into tissues, achieving clinically relevant concentrations in serum, kidneys, bladder wall, prostate, lungs, inflamed tissues, bone, cerebrospinal fluid, abscess fluid, and heart valves. Fosfomycin is well tolerated, with a low incidence of adverse events. Further randomized controlled trials are needed in order to evaluate the efficacy of intravenous fosfomycin for the management of nosocomial infections due to MDR pathogens.

Colistin: recent data on pharmacodynamics properties and clinical efficacy in critically ill patients.

Recent clinical studies performed in a large number of patients showed that colistin "forgotten" for several decades revived for the management of infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB) and had acceptable effectiveness and considerably less toxicity than that reported in older publications. Colistin is a rapidly bactericidal antimicrobial agent that possesses a significant postantibiotic effect against MDR Gram-negative pathogens, such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. The optimal colistin dosing regimen against MDR GNB is still unknown in the intensive care unit (ICU) setting. A better understanding of the pharmacokinetic-pharmacodynamic relationship of colistin is urgently needed to determine the optimal dosing regimen. Although pharmacokinetic and pharmacodynamic data in ICU patients are scarce, recent evidence shows that the pharmacokinetics/pharmacodynamics of colistimethate sodium and colistin in critically ill patients differ from those previously found in other groups, such as cystic fibrosis patients. The AUC:MIC ratio has been found to be the parameter best associated with colistin efficacy. To maximize the AUC:MIC ratio, higher doses of colistimethate sodium and alterations in the dosing intervals may be warranted in the ICU setting. In addition, the development of colistin resistance has been linked to inadequate colistin dosing. This enforces the importance of colistin dose optimization in critically ill patients. Although higher colistin doses seem to be beneficial, the lack of colistin pharmacokinetic-pharmacodynamic data results in difficulty for the optimization of daily colistin dose. In conclusion, although colistin seems to be a very reliable alternative for the management of life-threatening nosocomial infections due to MDR GNB, it should be emphasized that there is a lack of guidelines regarding the ideal management of these infections and the appropriate colistin doses in critically ill patients with and without multiple organ failure.

Pharmacokinetic evaluation of colistin sodium.

IMPORTANCE OF THE FIELD: Although colistin has recently played a key role in the treatment of nosocomial infections due to multidrug resistant Gram-negative pathogens, there is a lack of clinical studies examining colistin pharmacokinetics (PKs) in humans. This refers to all routes of colistin administration in clinical practice. Colistin PK data are also limited in critically ill patients. AREAS COVERED IN THIS REVIEW: Literature search took into account data dealing with colistin PK obtained from animal studies performed during previous decades (1970s, 1980s and 1990s) and from recent human studies performed during the last decade. WHAT THE READER WILL GAIN: Valuable information on pharmacodynamics (PD)/PK of colistin used in the treatments of nosocomial infections due to multidrug resistant Gram-negative pathogens, mostly Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. A better understanding of PKs could offer significant improvement of colistin use in humans, especially optimization of colistin doses in different routes of administration in order to maximize clinical efficacy and minimize adverse effects and rate of resistance. TAKE HOME MESSAGE: There is a lack of human studies on colistin PK and PD. Significant PD parameters best predicting colistin efficacy and their optimal values such as C(max):MIC ratio, AUC/MIC and T > MIC have not yet been clearly defined. It should be noted that further investigation on colistin PK/PD in vitro and in vivo models is required.

Multidrug-resistant Gram-negative infections: the use of colistin.

The emergence of nosocomial infections due to multidrug-resistant Gram-negative bacteria led to the revival of 'forgotten' antibiotics, such as polymyxins. Colistin, mainly colistimethate sodium (polymyxin E), has been predominantly used. Recent studies suggest that colistin administered as monotherapy or combination therapy is an effective and safe antimicrobial agent for multidrug-resistant Gram-negative bacteria infections. The reported colistin nephrotoxicity is 20% or lower. Although colistin is commonly administered intravenously, it can also be administered via inhalation for pneumonia/ventilator-associated pneumonia treatment or by the intraventricular/intrathecal route for meningitis/ventriculitis treatment. Randomized controlled trials are needed to answer clinical questions such as the appropriate colistin dose, to compare colistin monotherapy with combination therapy, and to determine the exact therapeutic role of aerosolized or intrathecal/intraventricular administration of colistin.

Impact of obesity on outcome of patients undergoing off-pump coronary artery bypass grafting using aorta no-touch technique.

We prospectively examined 1359 adult patients undergoing isolated coronary revascularization with the Pi-circuit technique, consisting of beating heart, aorta no-touch, use of composite grafts, and off-pump arterial revascularization. Patients were divided into two groups based on body weight; Group A consisting of 295 (21.7%) obese patients [body mass index (BMI) > or =30 kg/m(2)] and Group B of 1064 (79.3%) non-obese patients (BMI <30 kg/m(2)). Advanced age and emergency surgery favored the non-obese group [63.0+/-10.4 vs. 65.3+/-9.6 years (P<0.0005) and 10.2% vs. 17.1% (P=0.004), with an increase in the number of octogenarians among them (1.7% Group A vs. 5.4% in Group B, P=0.11)]. The use of double internal mammary arteries (90.5% in Group A vs. 86.9% in Group B, P=0.109), the mean number of distal anastomoses (2.8+/-0.9 in Group A vs. 2.7+/-0.9 in Group B, P=0.5) and the number of sequential anastomoses performed (28.1% in Group A vs. 31% in Group B, P=0.3) were similar. No difference in morbidity rates was detected. All cause in-hospital mortality was comparable. Survival was similar in both groups also. Obesity is not a risk factor for morbidity and mortality in this group of patients.

A bibliometric analysis by geographic area of published research in several biomedical fields, 1995-2003.

We summarized the findings of several studies of ours to compare the quantity and quality of published research from around the world for the years 1995 to 2003. We evaluated the number of articles published and their mean journal impact factor. We also studied the research productivity of various areas adjusted for gross domestic product (GDP) and population. We found that Western Europe leads the world in published research on infectious diseases-microbiology (82,342 articles [38.8%]) and in cardiopulmonary medicine (67,783 articles [39.5%]), whereas the United States ranks first in the fields of preventive medicine, public health and epidemiology both in quantity (23,918 articles [49.1%]) and quality of published papers. However, after adjustments for GDP, Canada ranked first, with the United States and Oceania following closely behind. All of the developing regions had only small research contributions in all of the biomedical fields examined.

An evaluation of McCoy balloon laryngoscopy in patients with moderate-to-major endotracheal intubation difficulty.

UNLABELLED: We hypothesized that combined McCoy-balloon laryngoscopy may facilitate airway management relative to McCoy or balloon laryngoscopy. In 10 anesthetized/paralyzed patients with prior intubation difficulty scale scores of >5, McCoy-balloon laryngoscopy versus conventional/balloon/McCoy laryngoscopies resulted in greater laryngeal aperture exposure (2.3 +/- 0.6 versus 0.6 +/- 0.2/1.4 +/- 0.4/1.5 +/- 0.6 cm2, respectively), lower intubation difficulty scale score (0.00 (0.00-0.00) versus 6.00 (6.00-8.25)/1.50(0.00-4.00)/2.00(0.75-5.00), respectively, median [interquartile range]), and 9%-74% shorter time to intubation confirmation (P < 0.05-0.001 for all). Balloon and McCoy laryngoscopies improved laryngoscopic/intubating conditions relative to conventional laryngoscopy. In patients with moderate-to-major conventional airway management difficulty, McCoy-balloon laryngoscopy further improves laryngoscopic/intubating conditions. IMPLICATIONS: This study shows that, in patients with moderate-to-major conventional airway management difficulty, combined McCoy-balloon laryngoscopy results in improved laryngoscopic/intubating conditions when compared with the conventional, McCoy, and balloon laryngoscopic techniques. McCoy-balloon laryngoscopy combines the merits of McCoy and balloon laryngoscopy and can be recommended for patients with moderate-to-major intubation difficulty.

Determinants of candidemia and candidemia-related death in cardiothoracic ICU patients.

STUDY OBJECTIVES: To develop and prospectively validate models of independent predictors of candidemia and candidemia-related death in cardiothoracic ICU (CICU) patients. DESIGN: (1) An initial, prospective, one-center, case-control, independent predictor-model determining study; and (2) a prospective, two-center, model-validation study. SETTING: The initial study was performed at the 14-bed CICU of the Onassis Cardiac Surgery Center, Athens, Greece; the model-validation study was performed at the Onassis Cardiac Surgery Center CICU and the 12-bed CICU of Henry Dunant General Hospital, Athens, Greece. PATIENTS: In the initial study, 4,312 patients admitted to the Onassis Center CICU between March 1997 and October 1999 were considered for enrollment; 30 candidemic and 120 control patients (case/control ratio, 1/4) matched according to potential confounders were ultimately enrolled. In the model-validation study, 2,087 patients admitted to the Onassis and Henry Dunant CICUs between November 1999 and May 2002 were prospectively enrolled. MEASUREMENTS AND RESULTS: Models of predictors of candidemia and associated death were constructed with stepwise logistic regression and subsequently validated. Independent candidemia predictors were ongoing invasive mechanical ventilation (IMV) > OR =10 days, hospital-acquired bacterial infection and/or bacteremia, cardiopulmonary bypass duration > 120 min, and diabetes mellitus. Model performance was as follows: sensitivity, 53.3%/57.9%; specificity, 100%/100%; positive predictive value (PPV), 100%/100%; negative predictive value (NPV), 88.9%/99.6%; and accuracy, 90.1%/99.6% (initial/model-validation study values, respectively). IMV > or =10 days and hospital-acquired bacterial infection/bacteremia were the two strongest candidemia predictors. APACHE (acute physiology and chronic health evaluation) II score > or =30 at candidemia onset independently predicted candidemia-related death with 80.0%/85.7% sensitivity, 80%/75% specificity, 66.7%/66.7% PPV, 88.9%/88.9% NPV, and 80.0%/78.9% accuracy (initial/model-validation study values, respectively). CONCLUSIONS: We provided a set of easily determinable independent predictors of the occurrence of candidemia in CICU patients. Our results provide a rationale for implementing preventive measures in the form of independent predictor control, and initiating antifungal prophylaxis in high-risk CICU patients.

Prone position improves lung mechanical behavior and enhances gas exchange efficiency in mechanically ventilated chronic obstructive pulmonary disease patients.

UNLABELLED: Pronation might favorably affect respiratory system (rs) mechanics and function in volume-controlled, mode-ventilated chronic obstructive pulmonary disease (COPD) patients. We studied 10 COPD patients, initially positioned supine (baseline supine [supine(BAS)]) and then randomly and consecutively changed to protocol supine (supine(PROT)), semirecumbent, and prone positions. Rs mechanics and inspiratory work (W(I)) were assessed at baseline (0.6 L) (all postures) and sigh (1.2 L) (supine(BAS) excluded) tidal volume (V(T)) with rapid airway occlusion during constant-flow inflation. Hemodynamics and gas exchange were assessed in all postures. There were no complications. Prone positioning resulted in (a) increased dynamic-static chest wall (cw) elastance (at both V(Ts)) and improved oxygenation versus supine(BAS), supine(PROT), and semirecumbent, (b) decreased additional lung (L) resistance-elastance versus supine(PROT) and semirecumbent at sigh V(T), (c) decreased L-static elastance (at both V(Ts)) and improved CO(2) elimination versus supine(BAS) and supine(PROT), and (d) improved oxygenation versus all other postures. Semirecumbent positioning increased mainly additional cw-resistance versus supine(BAS) and supine(PROT) at baseline. V(T) W(I)-sub-component changes were consistent with changes in rs, cw, and L mechanical properties. Total rs-W(I) and hemodynamics were unaffected by posture change. After pronation, five patients were repositioned supine (supine(POSTPRO)). In supine(POSTPRO), static rs-L elastance were lower, and oxygenation was still improved versus supine(BAS). Pronation of mechanically ventilated COPD patients exhibits applicability and effectiveness and improves oxygenation and sigh-L mechanics versus semirecumbent ("gold standard") positioning. IMPLICATIONS: By assessing respiratory mechanics, inspiratory work, hemodynamics, and gas exchange, we showed that prone positioning of mechanically ventilated chronic obstructed pulmonary disease patients improves oxygenation and lung mechanics during sigh versus semirecumbent positioning. Furthermore, certain pronation-related benefits versus preprone-supine positioning (reduced lung elastance and improved oxygenation) are maintained in the postprone supine position.

Acute postoperative pulmonary thromboembolism as a result of intravascular migration of a pigtail ureteral stent.

IMPLICATIONS: The symptomatic obstruction of a pulmonary arterial branch secondary to the intravascular migration of a pigtail ureteral stent is reported. This iatrogenic complication may cause dyspnea, chest pain, or both after uneventful urologic procedures involving ureteral stents.