De-escalation of antimicrobial therapy for bacteraemia due to difficult-to-treat Gram-negative bacilli.

PURPOSE: To examine the status and clinical outcome of de-escalating antimicrobial therapy for bacteraemia due to hospital-acquired, Gram-negative bacilli that are difficult to treat. METHODS: Among 1,610 patients presenting with positive blood cultures collected at our medical centre over a 6-year period, 133 were infected with Serratia, Pseudomonas, Acinetobacter, Citrobacter or Enterobacter sp. (SPACES). We examined the appropriateness of an empiric initial administration of antimicrobials based on in vitro sensitivity, and the success and outcomes of a pathogen-directed de-escalation of therapy. The treatment was considered to be successfully de-escalated when the antimicrobial spectrum was narrowed according to a spectrum ranking or when ≥ 2 antimicrobials prescribed initially were lowered to one agent. Outcome measures included persistent, recurrent and metastatic infections, infection-related deaths and cost of antimicrobials. RESULTS: The treatment was initially appropriate in 79 of 133 patients (59 %), of whom 49 (62 %) were candidates for and 28 (57 %) underwent treatment de-escalation. No treatment failure was observed among these 28 patients, while 2 of 11 patients (18 %) whose treatment was not de-escalated died (p = 0.13). The median cost of antimicrobials was 250/patient lower in the de-escalated than in the non-de-escalated group (p < 0.001). CONCLUSIONS: Antimicrobial therapy for bacteraemia due to hard-to-treat SPACES was de-escalated in 57 % of candidates, based on the in vitro sensitivity, with no deaths and significantly lower costs of antimicrobial therapy.

Effects of renal function on the pharmacokinetics and pharmacodynamics of prophylactic cefazolin in cardiothoracic surgery.

The purpose of this investigation was to study the effects of renal function on the pharmacokinetics and pharmacodynamics (PK-PD) of free cefazolin administered prophylactically in cardiothoracic surgery. Patients received an initial 2-g dose of cefazolin, followed by 1-g doses 6, 12, 18 and 24 h after the first dose. In patients who underwent cardiopulmonary bypass, 1 g was added to the priming solution. In 35 patients with a normal estimated creatinine clearance (CLcr) ≥50 ml/min, a free cefazolin concentration <4 µg/ml was observed in 11.4, 5.7 and 54.3% of patients before the second dose, at the end and 24 h after operation, respectively. In contrast, only 7.4% of 27 patients with CLcr <49 ml/min had a free cefazolin concentration <4 µg/ml 24 h after the operation. There was a high negative correlation between CLcr and time above the target minimal inhibitory concentration (MIC) when the CLcr was <50 ml/min (r(2) = 0.807), and no correlation when the CLcr was ≥50 ml/min. Renal function has a significant impact on the PK-PD of prophylactic cefazolin in cardiothoracic surgery. The postoperative drug dosing intervals should be <6 h in order to achieve a 100% time above the MIC in patients with CLcr ≥ 50 ml/min.

De-escalation of antimicrobials in the treatment of bacteraemia due to antibiotic-sensitive pathogens in immunocompetent patients.

BACKGROUND: The aim of this study was to examine the safety and efficacy of de-escalating antimicrobial therapy in immunocompetent patients presenting with bacteraemia due to antibiotic-sensitive pathogens. METHODS: We screened 1,350 positive blood cultures identified in a single, 1,065-bed university hospital over 5 years, and retained 310 cases of bacteraemia due to antibiotic-sensitive pathogens, including (1) methicillin-sensitive staphylococci, (2) penicillin-sensitive streptococci, (3) ß-lactam-sensitive (a) Escherichia coli, and (b) Klebsiella species. The efficacy of appropriate initial empirical antimicrobial therapy, the performance of de-escalated pathogen-directed therapy, and the safety and efficacy of de-escalated therapy were evaluated. RESULTS: Among 270 appropriately treated patients, 16 (6%) died, versus 6 (15%) among 40 who were inappropriately treated (p = 0.04). While 201 of 270 patients (74%) who received appropriate initial empirical therapy were candidates for de-escalation, the treatment was de-escalated in only 79 (39%). De-escalation was associated with (1) a trend toward a lower (a) death rate (1 vs. 5%) and (b) treatment failure (4 vs. 10%), and (2) (a) a 4-day longer median duration and (b) a $50 higher median cost of antimicrobial therapy (p < 0.001). CONCLUSIONS: When the pathogen was sensitive to antimicrobial therapy and the initial empirical treatment was effective, de-escalation of antimicrobial therapy in immunocompetent patients with bacteraemia was safe and associated with acceptable outcomes. The rate of de-escalation of antimicrobial therapy was low.

The importance of a judicious and early empiric choice of antimicrobial for methicillin-resistant Staphylococcus aureus bacteraemia.

The purpose of this investigation was to examine the impact of antimicrobial regimens administered for hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia on the all-cause, 14-day mortality. We retrospectively examined the characteristics of the most effective empiric antimicrobial therapy in 87 consecutive patients, hospitalised at a single institution between April 2003 and March 2008, who presented with clinically and microbiologically confirmed MRSA bacteraemia. The all-cause mortality was measured 14 days after the diagnosis was made. The administration of an effective antimicrobial against MRSA <48 h after the collection of blood cultures was the single, significant predictor of survival (odds ratio 3.85; 95% confidence interval 1.37-10.80; p = 0.01). The survival of patients treated with vancomycin versus other antimicrobial agents was similar. Among subgroups treated with vancomycin, the lowest mortality (6%) was observed among patients treated (a) within 48 h after the collection of blood cultures and (b) with doses sufficient to keep the blood concentrations in the area under the 0-24 h curve >400 µg h/ml (≥2.0 g/day). The empiric administration of antimicrobials effective against MRSA bacteraemia within 48 h after the collection of blood cultures increased the 14-day survival. If vancomycin is chosen, ≥2.0 g/day should be administered, starting within 48 h.

Eradication of the commensal intestinal microflora by oral antimicrobials interferes with the host response to lipopolysaccharide.

The host components and commensal microorganisms of the intestinal microenvironment play roles in the development and maintenance of the host defence. Recent observations have suggested that toll-like receptors (TLRs) are involved in the recognition of innate immunity against intestinal microbes. However, little is known regarding the role of TLR in the maintenance of systemic host defence by intestinal microorganisms. We studied the expression and function of TLR4 and TLR2 on alveolar and peritoneal macrophages in mice after 3 weeks of oral administration of streptomycin and cefotaxime. After active treatment, the intestinal microorganisms were nearly completely eradicated, and the surface expression of TLR4 and TLR2 on the peritoneal macrophages was prominently downregulated. When the actively treated mice were challenged with lipopolysaccharide (LPS), a TLR4 ligand, the host response was markedly impaired. Our results suggest that the oral administration of antimicrobials downregulates the expression of surface TLR on the peritoneal macrophages and modulates the host immune responses against LPS by modifying the intestinal environment.

Transillumination by light-emitting diode facilitates peripheral venous cannulations in infants and small children.

BACKGROUND: Transillumination facilitates the visualization of peripheral veins in infants and children. The clinical usefulness of light-emitting diode (LED)-powered devices has not been thoroughly studied. METHODS: We randomly assigned 136 infants and children weighing <15 kg, undergoing general anesthesia, to red LED-powered transillumination (TM group, n=67) vs. the usual method (UM group, n=69) of peripheral venous cannulations. Venous puncture was performed following anesthesia induction with sevoflurane and nitrous oxide. The primary and secondary study endpoints were the rate of successful cannulations at initial attempt, and the duration of insertion attempts, respectively. RESULTS: The median score of the estimated cannulation difficulty before attempted puncture was similar in both groups. The success rates at first attempt were 75% and 61% (NS) and mean+/-SD times to successful venous access were 47+/-34 and 68+/-66 s (NS) in the TM and UM groups, respectively. The cannulation procedures were completed significantly earlier in the TM group than in the UM group (hazard ratio, 1.59; 95% confidence interval, 1.03-2.47; P=0.03). In the subgroup of infants and children <2 years old, venous cannulation was successful at first attempt in 73% and 49% in the TM group (n=44) and in the UM group (n=47), respectively (P=0.03). CONCLUSIONS: LED-powered transillumination devices facilitated peripheral venous cannulations in small infants and children.

Disseminated aspergillosis following resolution of Pneumocystis pneumonia with sustained elevation of beta-glucan in an Intensive Care Unit: a case report.

Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients receiving intensive care. The double-sandwich ELISA for galactomannan is reported to have a high sensitivity (96.5%) for the detection of invasive aspergillosis when a cut-off value of 0.8 ng/ml is used. However, we have experienced a case of lethal disseminated aspergillosis in a patient that presented with a negative galactomannan (GM) test and persistent elevation of beta-D glucan (BG) levels. A 63-year-old female was admitted to our Intensive Care Unit (ICU) in acute respiratory failure and elevated BG. She had been receiving medication for Good-pasture syndrome based on anti-glomerular basement membrane antibodies and myeloperoxidase-antineutrophil cytoplasmic antibodies for 9 months and was receiving long-term prednisolone therapy (20 mg/day). On admission, her trachea was immediately intubated, and a PCR analysis of the bronchoalveolar lavage sample revealed Pneumocystis jiroveci. Trimethoprimsulfamethoxazole therapy was started for Pneumocystis pneumonia. The levels of BG remained elevated (> 100 pg/ml) during the treatment period despite the clinical resolution of Pneumocystis pneumonia, raising concerns of another complicated invasive fungal disease; consequently, fosfluconazole was administered empirically. The serum BG levels, however, did not decrease. Blood cultures did not detect a fungal infection. Serum GM levels measured by a double-sandwich ELISA on the 6th, 11th, and 24th days in the ICU were negative (< 0.2 ng/ml). The patient ultimately died of multiple organ failure on the 45th ICU day. Postmortem examination revealed a disseminated fungal infection with aggressive vascular invasion of the lungs, heart, and brain. In situ hybridization with a 568-bp probe of the alkaline proteinase sequence of Aspergillus fumigatus showed specific positive staining within the fungus present in the infected lung tissue, revealing that this patient may have had a systemic infection by A. fumigatus or A. flavus. This is a case of serum GM-negative disseminated aspergillosis pathologically proven by autopsy. Persistent elevated BG levels (> 100 pg/ml) refractory to trimethoprim-sulfamethoxazole and fosfluconazole may suggest possible Aspergillus infection and should prompt the initiation of empiric anti-aspergillosis therapies in patients at risk for fungal infection.

Successful treatment of traumatic spinal epidural haematoma with fluoroscopically-guided percutaneous drainage: a report of two cases.

We report two cases of spinal epidural haematoma that were successfully treated with percutaneous drainage. The patients initially presented with severe backache and progressive neurological symptoms due to traumatic epidural haematoma. After fluoroscopically-guided percutaneous drainage and irrigation, rapid physical decompression and full recovery was observed in both patients. To the best of our knowledge, this is the first report indicating that traumatic spinal epidural haematoma can be successfully treated with fluoroscopically-guided percutaneous drainage. Because percutaneous puncture under fluoroscopy is less invasive than surgery, we recommend considering this procedure as a non-operative treatment option for epidural haematoma.

Arterial ketone body ratio for the assessment of the severity of illness in pediatric patients following cardiac surgery.

PURPOSE: The purpose of this study was to assess whether the arterial ketone body ratio (AKBR) can be effectively used to evaluate the severity of illness in children following cardiac surgery. MATERIALS AND METHODS: AKBR was measured in 157 consecutive pediatric patients following heart surgery on the odd numbers of postoperative days. The relationship between AKBR and patient outcome was analyzed using the data of 141 patients with cardiopulmonary bypass. RESULTS: Initial AKBR was frequently lower than 1.0, and this was associated with the increases in total ketone body counts. Insufficient glucose metabolism appeared to contribute to the low initial AKBR. As a result, the specificity of initial AKBR as a mortality predictor was lower than that of initial blood lactate. In the sequential analysis of AKBR for the 48 patients with PICU stay longer than 5 days, patients showing a sustained lower level <1.0 had significantly higher development of organ dysfunction (liver, heart) and greater mortality (56%). CONCLUSIONS: Sustained postoperative decrease in AKBR <1.0 represents lethal outcome. The analysis of AKBR trend in combination with a measurement of blood lactate level in early postoperative period appears to be useful for the assessment of the severity of illness in pediatric patients following heart surgery.

Hypoxic gas therapy using nitrogen in the preoperative management of neonates with hypoplastic left heart syndrome.

OBJECTIVE: To evaluate the efficacy of hypoxic gas therapy using nitrogen, where the fraction of inspired oxygen (Fio2) was reduced to <0.21 in patients with univentricular parallel circulation. DESIGN: Case report. SETTING: A pediatric intensive care unit at a university hospital. PATIENTS: Two neonatal patients with hypoplastic left heart syndrome admitted to the pediatric intensive care unit preoperatively. INTERVENTIONS: Nitrogen insufflation by using continuous-flow respiratory support. MEASUREMENTS AND MAIN RESULTS: We reduced the Fio2 in these patients by giving additional nitrogen to relieve pulmonary overcirculation and systemic hypoperfusion suspected by transcutaneous arterial oxygen saturation >90%, systemic arterial hypotension, and low urine output in the preoperative course. The improvement of systemic hemodynamics concomitant with decreases in transcutaneous arterial oxygen saturation <85% was accomplished by controlling Fio2 between 0.14 and 0.18. These infants were able to undergo Norwood's surgery after several days without complications relating to Fio2 reduction. CONCLUSION: Hypoxic gas therapy with nitrogen was effective clinically in preventing pulmonary overcirculation in neonatal patients with univentricular and parallel circulation.

[Anesthetic management for surgery of patients with metastatic brain tumors associated with lung tumors].

We had four patients who received anesthesia for metastatic brain tumors. All patients were complicated with primary lung tumors which had caused several respiratory problems. Respiratory failure and intratracheal hemorrhage from lung tumors were the severest complications during and after the operation. Two patients suffered from pneumonia at early postoperative stage and died of respiratory failure within eighty days after the operation. We consider that these preoperative findings of atelectasis and hemosputum are important signs that could predict those severe complications. To avoid postoperative respiratory complications in patients with atelectasis, the anesthetist should perform careful perioperative management such as active preoperative pulmonary physical therapy and should choose anesthetics which do not affect postoperative consciousness and respiration, and should perform intensive postoperative respiratory care. To prevent pulmonary hemorrhage, the fiberoptic bronchoscopy is useful for the diagnosis and the therapy. We also consider that the long operation aggravates postoperative complications. Planning of operation and performing operative procedure in a shortest time possible are also important.

[Anesthetic management of a patient with progressive spinal muscular atrophy].

Various problems especially weakness of respiratory muscle and abnormal reaction to muscle relaxant exist during the management of anesthesia for the patients with neuromuscular disease with the disturbance of motor neurons. We had a patient for trans-urethral resection of prostate with spinal progressive muscular atrophy. Using nitrous oxide-oxygen with halothane, and without muscle relaxant, we succeeded in avoiding respiratory failure, aspiration and other serious complications. By measuring serum sodium, rapid discovery and treatment of water intoxication could be achieved.

[A case of rhabdomyolysis after open heart surgery in a child].

Rabdomyolysis usually occurs after trauma and release of myoglobin from the damaged muscle, i.e.; after ishchemic myopathy due to arterial occlusion or malignant hyperthermia. We encountered a pediatric case of rhabdomyolysis after Ross-Konnos' operation in an 8-yr-old girl with aortic regurgitation. After the first weaning from cardiopulmonary bypass (CPB), ventricular fibrillation occurred due to an insufficiency in coronary blood flow and CPB was resumed with rapid cooling of body temperature. The total CPB lasted for 5 hr 43 min. After the second weaning from CPB, myoglobinuria was found. Furthermore, blisters and abrasions appeared on her back and CPK levels were abnormally elevated (maximum 19,132 IU.l-1) without any elevation of body temperature in the postoperative course. Rhabdomyolysis due to intraoperative hypoperfusion was suspected and diuretics were administrated with a large amount of crystalloid to maintain urine output. The patient showed a good clinical course without acute renal failure. The course of this case suggests that rhabdomyolysis is one of rare complications of CPB and an early correct diagnosis of rhabdomyolysis and forced diuresis at an early stage are important to avoid acute renal failure.

[Usefulness of transcutaneous gas monitoring during hemorrhagic shock].

This study was undertaken to confirm whether transcutaneous (tc) gas analysis during hemorrhagic shock could be used as an alternative to mixed venous gas analysis. Tc gases were measured and correlated with arterial and mixed venous gases in 10 anesthetized dogs during hemorrhagic shock and volume resuscitation. Throughout this experiment PtcO2 correlated well with PvO2 (r = 0.78, P less than 0.01), while PaO2 remained mostly constant, and PtcCO2 correlated well with PvCO2 (r = 0.82, P less than 0.01) rather than with PaCO2 (r = 0.63, P less than 0.01). A more detailed observation showed that during progressively decreased cardiac output, PtcO2 became lower than PvO2 and PtcCO2 became higher than PvCO2. We inferred from these observations that the changes of tc and mixed venous gases reflected those gases in tissues and that during severe shock maldistribution of peripheral blood flow prevented mixed venous gases from coming into equilibrium with tissue and tc gases. We conclude that the measurement of tc gases during shock is a more convenient and more reliable monitor of tissue gases than mixed venous analysis.

[The usefulness of transcutaneous gas monitoring during hemorrhagic shock; discrepancy between the two transcutaneous gas tensions of anterior thorax and femur].

We measured transcutaneous gas tensions of both anterior thorax and femur. The differences between the two transcutaneous gas tensions were compared, as well as the relationship between the two transcutaneous and mixed venous blood gas tensions, in 10 dogs during hemorrhagic shock. The changes in femoral transcutaneous gas tensions correlated better with the changes in mixed venous gas tensions. The correlation between the two transcutaneous gas tensions were fairly good (oxygen tensions; r = .827, carbon dioxide tensions; r = .867). However, the discrepancy between the two gas tensions became greater in severe shock. Hence, oxygen tensions became smaller and carbon dioxide tensions became greater on femur than on anterior thorax. This indicates the possibility of "maldistribution of blood flow", which has already been detected between vital organs and skin, also exists between peripheral and central skin. Therefore, transcutaneous gas tensions should be monitored at peripheral skin, where gas tensions show greater changes and reflect systemic perfusion precisely than at central skin, during shock.

[Assessment of oxygen transport in individual splanchnic organs using critical oxygen extraction].

Vulnerability in individual organs under ischemic stress can be assessed by critical oxygen extraction (critical O2ER). We measured critical O2ER in the whole-body, total splanchnic organs, liver and gut using a biphasic regression model of the oxygen delivery-consumption relationship in 7 dogs subjected to hemorrhagic stress under 1% isoflurane anesthesia. The difference in critical O2ER between the whole-body and total splanchnic organs was not significant, while hepatic critical O2ER was significantly larger than that of the gut (P < 0.05), 89.7 +/- 2.4% (mean +/- SD) and 66.1 +/- 5.1%, respectively. This finding indicated that the liver functions well under ischemic conditions due to its excellent ability to extract oxygen. The anatomical character of the sinusoid and the microcirculatory improving effect of isoflurane may affect the ability of oxygen extraction of the liver. The critical threshold of hepatic venous oxygen saturation as a marker of hepatic oxygen imbalance was considered to be below 10%.

[Perioperative assessment of blood lactate levels in pediatric heart surgery].

Measuring arterial lactate concentration is a prompt, easy and relatively non-invasive way to estimate tissue oxygen metabolism. We evaluated whether perioperative levels of the arterial lactate concentrations can reflect the general severity of a pediatric patient's condition. A consecutive series of 112 patients, aged 5 days to 17 years (median age: 12 months), admitted to our pediatric intensive care unit (PICU) following cardiac surgery under cardiopulmonary bypass were studied. Arterial blood lactate concentration was measured preoperatively, immediately upon termination of the cardiopulmonary bypass (postCPB), immediately following the operation, and 16th hours postoperatively (D1). Trends within arterial lactate concentrations were examined in relation to mortality rates, the duration of PICU stays and the patient's ages. The studied population had a mortality rate of 5.7% (6 patients). Lactate levels increased significantly and exceeded 4.0 mmol.l-1 during postCPB measurements in a majority of the patients. The increases in lactate levels are affected by the changes in interorgan blood flow, blood glucose levels and/or blood pH in addition to the effects of the CPB-priming lactated Ringer's solution. Thus, higher cut off values have to be determined, and lower probabilities assigned, when using postCPB lactate levels to predict the severity of an outcome. Significantly and sustained increases in D1 lactate levels were noted in neonates, patients with longer PICU stays (> 15 days) and those died later. Hyperlactemia greater than 2.2 mmol.l-1 at D1 predicted death with a sensitivity of 82% and a specificity of 72%. The measurement of early postoperative lactate levels, reflecting postoperative ability to eliminate intraoperative hyperlactemia, is a better way of assessing the severity of a pediatric patient's condition following cardiac surgery. The ideal time to measure early postoperative lactate levels should be determined by further research.

Cardiovascular changes during continuous hyperthermic peritoneal perfusion.

Changes in blood temperature, hemodynamics, and oxygen transport were evaluated in 11 patients during continuous hyperthermic peritoneal perfusion (CHPP), a technique in which the peritoneal cavity is perfused continuously with heated solution to treat intraperitoneal cancer. CHPP was undertaken 46.8 min after the resection of cancer. Blood temperature, measured with a thermistor of a pulmonary artery catheter, reached 39.2 degrees C. Heart rate increased to 100.7 +/- 21.4 bpm (mean +/- SD) and the cardiac index to 4.61 +/- 0.80 L.min-1.m-2. Mean arterial pressure decreased to 75.5 +/- 10.8 mm Hg and systemic vascular resistance index to 1239 +/- 394 dynes.s.cm-5.m2. Oxygen consumption greatly increased to 139.1 +/- 35.2 mL.min-1.m-2, concurrently with a smaller increase in oxygen delivery to 619.7 +/- 83.7 mL.min-1.m-2 and a slight increase in oxygen extraction. Pulmonary oxygenation capacity was also disturbed. Although these cardiovascular changes were mainly due to systemic hyperthermia, other changes may be caused by splanchnic heating, abdominal distention, and pharmacologic action of methoxamine, propranolol, diltiazem, and fentanyl.