Administration Of Antibiotic Therapy Research Articles

THE RESULTS OF MECHANICAL HEART SUPPORT SYSTEMS «INCOR» IMPLANTATION

The aim of investigation isestimation of mechanical heart support system «INCOR» implantation ef fi cacy. Materials and methods. The Institute of Circulation Pathology has clinical experience of mechanical circulatory support systems «INCOR» (Berlin Heart AG) implantation in 12 patients (10 men and 2 women) with severe heart failure during the period from November 2006 to October 2012. The main indication for the use of mechanical support of the left ventricle was a left ventricular failure with marked dilatation of the left heart: end-diastolic volume (EDV), LV – 283 ± 58 ml, end-systolic volume (ESV) – 233 ± 57 ml, ejection fraction (EF) – 16 ± 7%, with preserved function of the right ventricle (RV) (RV ejection fraction 35 ± 12%). Results. All patients showed a signi fi cant improvement in central hemodynamics in early postoperative period, reducing the volume of the heart chambers: LV EDV from 283 ± 58 to 183 ± 94 ml; LV ESV with 234 ± 57 to 157 ± 65 ml, increased right ventricular ejection fraction (RV EF ) (from 35 ± 12 to 43 ± 17%). Improve the function of the right ventricle oc- curred mainly due to the expense of left ventricular unloading and pulmonary circulation. In addition, there was a signi fi cant improvement in clinical status of patients – regression of symptoms of heart failure, a recovery of the liver and kidney function. Despite the ongoing anticoagulation and antiplatelet therapy under constant parameters of coagulation, there was some complications. Uterine bleeding occurred in 1 patient (16.6%), which required the abolition of anticoagulants and antiplatelet, uterine artery embolization, and as a result has led to thrombosis and stop system «INCOR». Four patients (33.3%) had severe thromboembolic complications – acute cerebrovascular accident (CVA). In 1 patient (8%) there was a hemorrhagic stroke due to rupture of intracerebral aneurysms with a breakthrough into the lateral ventricle of the brain. In 3 patients (25%) the late period (3–6 months after implan- tation) was accompanied by a purulent-septic complications, which required of antibiotic therapy administration. Time of INCOR functioning ranged from 17 to 948 days. Six patients (50%) underwent successful orthotopic car- diac transplantation at 180–948 days after left ventricle bypass system implantation. The remaining patients died from various complications: three patients from severe thromboembolic stroke, one patient died from hemorrha- gic stroke due to rupture of intracerebral aneurysms with a breakthrough into the lateral ventricle of the brain, one patient death was due to progressive right heart failure, another death occurred on background of chronic sepsis. Conclusion. Thus, implantable system for circulatory support «INCOR» using achieves signi fi cant regression of heart failure manifestations. But sadly, holding a mechanical heart support is associated with the risk of severe complications, such as thromboembolism, hemorrhagic stroke, sepsis and increase biventricular failure.

PRM9 - The implementation of the extract of centaria islandica in patients suffering from egzacerbation of chronic pharyngitis

The objective of this paper is to establish if the implementation of Isla lozenges influences the intensity of sore throat sensation in patients suffering from egzacerbation of chronic pharyngitis and whether their use influences the need of antibiotic therapy administration. The number of 60 patients with egzacerbation of chronic pharyngitis has been observed. 30 of them used Isla lozenges during 10 days/ 6 times a day, while the remaining 30 did not take any. According to the VAS scale (0-10 cm) the intensity of sore throat sensation was determined at the beginning of the disease and after 10 days. Also, it was determined in how many patients it was necessary to introduce antibiotic therapy. The average value of sore throat sensation in the initial stage in the group in which Isla lozenges were administered was 6.80, while in the group that did not take them was 6.60; p> 0,05. After ten days of trial, the average value in the group that took Isla lozenges was 1.60; p< 0,05. In the group that did not take the lozenges, the average sore troat sensation was 5.90 after ten days; p> 0,05. The average values of sore troat sensation after 10 days of Isla lozenges implementation were statistically significantly lower in comparison to the second group; p< 0,05. The group in which Isla lozenges were given for 10 days, 5 patients needed additional antibiotic therapy, whereas it was 14 patients in the second group; p< 0,05. Implementation of Isla lozenges in patients with egzacerbation of chronic pharyngitis statistically significantly lowers the intensity of sore throat sensation as well as the need for later antibiotic therapy administration. This research was supported by Provincial Secretariat for Science and Technological Development, Autonomous Province of Vojvodina project No 114-451-3551/2013-01

До питання етіологічної діагностики тонзилофарингітів у дітей

У статті проведений літературний аналіз сучасного стану проблеми ранньої діагностики тонзилофарингітів у дитячому віці, а саме своєчасної етіологічної діагностики захворювання. Висвітлені питання етіології, епідеміології, клініки, диференціальної діагностики, параклінічної діагностики, напрямки лікування тонзилофарингітів у дітей. Основна увага була приділена літературному огляду проблем і сучасним можливостям швидкої етіологічної діагностики тонзиліту в дітей, а також принципам раціональної антибактеріальної терапії та методам профілактики захворювання з позицій доказової медицини. У роботі наголошується на тому, що особливе значення має рання діагностика стрептококової етіології тонзилофарингіту, яка дозволяє на самому початку захворювання призначити обґрунтовану антибактеріальну терапію. Це призведе до скорочення тривалості хвороби, істотного зниження ризику ранніх ускладнень і значного скорочення періоду заразності пацієнта, що, у свою чергу, знижує ймовірність поширення стрептококової інфекції. Золотим стандартом виявлення β-гемолітичного стрептокока з метою призначення антибактеріальної терапії є стрептотест. Використання експрес-тестових систем у клініці дитячих інфекційних хвороб повинно покращити ранню етіологічну діагностику тонзилофарингітів у дітей і тим самим сприяти своєчасному адекватному призначенню лікування, що в кінцевому результаті має значно знизити ризик розвитку ускладнень та сприяти позитивному економічному ефекту.

Role of empirical and targeted therapy in hospitalized patients with bloodstream infections caused by ESBL-producing Enterobacteriaceae.

Bloodstream infection (BSI) due to extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae are a major cause of in-hospital mortality. The effect on survival of empirical and targeted antibiotic therapy in these patients remains controversial. A prospective cohort study was conducted analyzing data from 94 patients (age 59 ± 21 years) with BSI due to ESBL producing strains (Sixty-one E. coli, 26 K. pneumoniae, 4 Proteus spp and 3 Enterobacter spp). Risk factors associated with 21-day mortality at univariate analysis were: recent administration of antibiotic therapy (p=0.049), higher SOFA score (p=0.05), ICU stay (p <0.01), hypotension at presentation (p =0.001) or septic shock (p <0.001) and bacteremia from source other than urinary tract (p=0.03). Regardless of antibiotic class used, no differences in survival were noted between patients receiving or not adequate initial antimicrobial treatment (37.1% vs 23.7% p=0.23); on the other hand, compared with the administration of other in vitro active antibiotics, the use of carbapenem as definitive therapy was associated with a significantly lower 21-day mortality (54.3% vs 28.5% p=0.02). These findings suggest that the administration of an adequate initial therapy is not associated with mortality in hospitalized patients with BSI due to Enterobacteriaceae. The severity of clinical conditions at presentation and the administration of carbapenems as definitive therapy seems to be really important in affecting the outcome of patients with BSI due to ESBL producing strains.

Aggressive versus conservative initiation of antibiotics

Sepsis identification in critically ill patients is still a difficult task, and the right time to administer antibiotics after clinical signs have been detected remains an unsolved issue. Nevertheless, in cases of severe sepsis, early use of appropriate antibiotics seems logical, and many retrospective studies have shown a relation between delay in administration of antibiotic therapy and increased risk of death.1–3 Tjasa Hranjec and colleagues4 reported the results of a quasi-experimental study that compared outcomes of treatment with either an aggressive empirical antibiotic strategy or a more conservative strategy for patients admitted to a surgical intensive-care unit (ICU) with sepsis.

Nurse-Driven Protocols for Febrile Pediatric Oncology Patients

Infection is a frequent complication experienced by many children with cancer, with potentially life-threatening consequences that may result in hospitalization, prolonged length of stay, and increased mortality. The need for prompt assessment and early intervention for infection is widely recognized by ED staff as best practice; however, the average length of time to antibiotic administration varies widely in published studies. An interdisciplinary quality improvement initiative including physician, nursing, and pharmacy leaders was created to streamline the identification and treatment for this high-risk population. Based on published evidence for best practice and national recognition of the need for rapid treatment, the goal was set for administration of antibiotic therapy to less than 60 minutes after ED arrival. This project was conducted at 2 emergency departments in a pediatric health care system with 520 beds and a level I and level II trauma designation. Approximately 154,000 patients are seen annually. In the emergency departments, 271 staff members, including registered nurses, paramedics, and patient care technicians, required education about using the newly designed process. Records from all patients with fever and a known history of pediatric cancer who presented to the emergency departments were included in the retrospective review, including patients with solid tumors, acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myelogenous leukemia. Exclusion criteria included patients in known remission, those with prior antibiotic therapy at another facility, congenital neutropenia, or parental concern or objection to treatment. A retrospective medical record review of febrile oncology patients treated from September 2008 until May 2012 was conducted to evaluate the impact of this evidence-based practice change to streamline the "door to drug" process. The average length of time until antibiotic administration, nurses' compliance initiating the protocol, and ED length of stay were determined. The review included 2758 medical records. During the study period from 2008 to 2012, one emergency department's average time for drug administration dropped from 103 to 44 minutes, and the second dropped from 141 to 61 minutes. Both campuses also improved their protocol compliance, with ED 1 increasing from 24% to 78% and ED 2 improving from 30% to 84%. This quality initiative has direct application for all ED leaders who treat children with cancer. High-risk patients can benefit from a streamlined nurse-initiated process that decreases negative consequences of fever. Collaboration by interdisciplinary leadership within the health care facility, as well as key stakeholder buy-in, is imperative to achieve a process that may lead to decreased hospital stay and reduced systemic infection or mortality for these vulnerable patients.

Pharmacological stabilization of hypoxia inducible factors (HIF) enhances endothelial immunity against invasive gram positive bacterial pathogens

Bloodborne bacteria that target and invade the endothelium can cause life threatening syndromes such as meningitis and endocarditis. Even timely administration of antibiotic therapy may be ineffective if the infectious agent is a “superbug”, such as methicillin‐resistant Staphylococcus aureus (MRSA). Hypoxia‐inducible transcription factors (HIF) regulate energy homeostasis and cellular adaptation to low oxygen stress. The HIF‐1 isoform is also activated in response to infectious stimuli and augments the innate immune functions of white blood cells. Hypoxia mimicry through administration of the HIF‐stabilizing drug AKB‐4924 was previously shown to enhance the antibacterial activity of phagocytes and skin cells against MRSA, uncovering a new strategy in the treatment of superbugs. We show here that AKB‐4924 is also an effective activator of isoforms HIF‐1 and HIF‐2 in cultured endothelial cells. Pretreatment of cells rendered them more resistant to invasion by pathogenic Staphylococcus and Streptococcus, while concurrent treatment of sick cells limited the intracellular replication of these bacteria. Confirming a role of HIF in maintenance of the endothelial barrier against bloodborne disease, mice with endothelium‐targeted HIF deletions accumulated greater bacterial loads in organs including brains and hearts during bacteremic infection assays.

Persistence of ultrasound alterations after antibiotic treatment with levofloxacin in patients with male accessory gland infection

No studies have evaluated the ultrasound features of the male sex accessory glands in infertile patients with bacterial male accessory gland infection (MAGI) according to the microbiological outcomes of bacterial cultures (absent, partial or complete) following antibiotic therapy administration. Therefore, the aim of this study was to evaluate the ultrasound characteristics of the prostate, seminal vesicles, and epididymal tracts after treatment with levofloxacin (a common quinolone antibiotic), in patients with infections caused by Escherichia coli (a Gram-negative bacterium) according to the Naber's classification, which includes the following categories: eradication, eradication with superinfection, persistence and persistence with superinfection. The study was conducted in 100 patients aged 25±8 years (range: 20-40 years) with bacterial MAGI and bacterial cultures positive only for E. coli (colony forming units ≥10(6) per ml). Retrospective analysis was conducted only on patients treated with oral levofloxacin (500mg) administered once daily for 28 days who were recruited over the last 5 years. Following antibiotic treatment, patients with microbiological persistence or persistence with superinfection had a significantly higher percentage of ultrasound abnormalities suggestive of prostato-vesiculitis (PV) (30.2% and 36.0%, respectively) or prostato-vesiculo-epididymitis (PVE) (60.2% and 70.0%, respectively) compared with patients with microbiological eradication (PV=10.2% and PVE=8.2%, respectively) or eradication with superinfection (PV=18.8% and PVE=21.2%, respectively). In conclusion, patients with microbiological persistence or persistence plus superinfection showed the highest prevalence of complicated forms of MAGI (PV and PVE), compared with patients with microbiological eradication or eradication with superinfection.

Uncommon Cause of Chest Pain in a Renal Transplantation Patient With Autosomal Dominant Polycystic Kidney Disease: A Case Report

Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of end-stage renal disease (ESRD) and, because of its intrinsic systemic involvement, its treatment can be a medical and surgical challenge. This condition is often associated with the presence of hepatic cysts and their prevalence generally increases with age. Most patients remain asymptomatic, but some of these will develop complications associated with enlargement and infection of their cysts. Chest pain is a rare manifestation of these complications and, after exclusion of more common cardiovascular and pulmonary causes, should raise the suspicion of an infected hepatic cyst in these patients. We report the case of a 62-year-old male who underwent a kidney transplantation from a cadaveric donor in 1997 (etiology of the ESRD was ADPKD), and was admitted to the emergency department with complaints of chest pain radiating to both shoulders and the interscapular region. An echocardiogram was showed compression of the right atrium by a large liver cyst without associated ventricular dysfunction. Computer tomography–guided drainage of the cyst was performed and an Enterobacter aerogenes sensitive to carbamapenemes was isolated from respective cultures. The patient presented a favorable clinical outcome with prolonged administration of antibiotic therapy according to the antibiotic susceptibility testing. There was no need for surgical intervention.

Short- vs Long-Course Antibiotics for Acute Exacerbations of Chronic Bronchitis

The increasing prevalence of acute exacerbations of chronic bronchitis (AECB) is a significant public health problem, costing the United States health care system over $1.9 billion in 2008. While AECB is mainly treated with antibiotics, the ideal duration of antibacterial treatment remains unclear. Antibiotic overprescription, growing prevalence of bacterial resistance to antibiotics worldwide, and difficulties with patient adherence are ongoing issues. The purpose of this literature review is to identify the most effective duration of antibiotic therapy administration (short- vs long-course antibiotic therapy) for patients with AECB, synthesizing the findings for clinical application.

Septic arthritis of the knee: the use and effect of antibiotics prior to diagnostic aspiration

Septic arthritis of the native knee joint and total knee arthroplasty both cause diagnostic and treatment issues. There is no gold standard test to diagnose a joint infection and the use of joint aspiration is commonly relied on. It is widely accepted by orthopaedic surgeons that antibiotics should be withheld until aspiration has been performed to increase the odds of identifying an organism. Patients often present to other specialties that may not be as familiar with these principles.Our study found that 25 (51%) of the 49 patients treated for septic arthritis of the native or prosthetic knee in our unit over a 3-year period had received antibiotics prior to discussion or review by the on-call orthopaedic service. Patients were significantly less likely to demonstrate an organism on initial microscopy (entire cohort: p=0.001, native knees: p=0.006, prosthetic knees: p=0.033) or on subsequent culture (entire cohort: p=0.001, native knees: p=0.017, prosthetic knees: p=0.012) of their aspirate if they had received antibiotics. The sensitivity of microscopy in all patients dropped from 58% to 12% when patients had received antibiotics (native knees: 46% to 0%, prosthetic knees: 72% to 27%). The sensitivity of the culture dropped from 79% to 28% in all patients when the patient had received antibiotics (native knees: 69% to 21%, prosthetic knees: 91% to 36%).This study demonstrated how the management of patients with suspected cases of septic arthritis of the knee may be compromised by empirical administration of antibiotics. These patients were significantly less likely to demonstrate an organism on microscopy and culture of their initial aspirate. There is a significant high false negative rate associated with knee aspiration with prior administration of antibiotic therapy.

Prostatastanzbiopsien

The aim of the study was to evaluate the best anesthesia for transrectal prostate biopsy, the complications after biopsy, and the influence of the biopsy on the clinical outcome after radical prostatectomy. The analysis included 1,383 patients after radical prostatectomy. With respect to compliance the biopsy should be performed under anesthesia. The most efficient procedure for pain reduction is analgosedation. Periprostatic local anesthetic in combination with the application of a lidocaine-containing jelly is in alternative use. Antibiotic prophylaxis should be given in consideration of possible antibiotic resistance due to recently administered antibiotic therapy. The percentage of R1 resection is higher if only one prostate biopsy can detect the carcinoma and leads immediately to radical prostatectomy. When several biopsies are necessary to detect the carcinoma the percentage of R1 resection is lower. Repeated prostate biopsies have no effect on the patients' outcome after radical prostatectomy. The best time for radical prostatectomy in relation to urinary incontinence is 8 weeks after prostate biopsy.

Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) is the most frequent nosocomial infection in the intensive care unit (ICU), with an incidence ranging from 8% to 38%. Patients who acquire VAP have higher mortality rates and longer ICU and hospital stays. Because there are other potential causes of fever, leukocytosis, and pulmonary infiltrates, clinical diagnosis of VAP is overly sensitive. The only alternative approach to the clinical diagnosis of VAP is the Clinical Pulmonary Infection Score (CPIS). Employing quantitative cultures of respiratory secretions in the diagnosis of VAP leads to less antibiotic use and probably to lower mortality. With respect to microbiologic diagnosis, however, it is not clear that the use of invasive sampling using bronchoscopy is associated with better outcomes. Delayed administration of antibiotic therapy is associated with an increased mortality, and inadequate antibiotic therapy is also associated with higher mortality. Therefore, prompt initiation of adequate antibiotic therapy is a cornerstone of the treatment of VAP. The initial antibiotic therapy should be based on the most common organisms in each hospital and the most likely pathogens for that specific patient. When final cultures and susceptibilities are available, de-escalation to less broad spectrum antibiotics should be done. Since clinical improvement usually takes 2 to 3 days, clinical responses to the initial empirical therapy should be evaluated by day 3. A short course of antibiotic therapy appears to be equivalent to a traditional course of more than 14 days, except when treating non-fermenting gram-negative organisms. If patients receive initially adequate antibiotic therapy, efforts should be made to shorten the duration of therapy to as short as 7 days, provided that the etiologic pathogen is not a non-fermenting gram-negative organism.

Impact of the implementation of a sepsis protocol for the management of fluid-refractory septic shock: A single-center, before-and-after study

Background: Evidence-based guidelines have been published for the acute management of severe sepsis and septic shock. Key goals of institution-driven protocols include timely fluid resuscitation and antibiotic selection, as well as source control. Objective: This study assessed the impact of a sepsis protocol on the timeliness of antibiotic administration, the adequacy of fluid resuscitation, and 28-day mortality in patients with fluid-refractory septic shock. Methods: This was a single-center, before-and-after study (18 months before July 2007 and 18 months after) with prospective data collection evaluating the outcomes of a sepsis protocol in adult patients with fluid-refractory septic shock. All patients received a fluid challenge and antibiotics; those who did not were excluded from this analysis. Preprotocol findings led to the development of the sepsis protocol, which emphasized fluid resuscitation, timely administration of antibiotic therapy, and collection of specimens for culture at the onset of septic shock. In the pre- and postprotocol phases of the study, data were collected prospectively and analyzed for demographic characteristics; Acute Physiology and Chronic Health Evaluation (APACHE) II score; appropriateness of fluid resuscitation; antibiotic use; number of vasopressor, ventilator, and intensive care unit (ICU) days; and 28-day mortality. Outcomes were measured prospectively at any time during the patient's hospital admission. The primary end points were the time to administration of antimicrobial therapy and the appropriateness of fluid resuscitation before and after implementation of the sepsis protocol. Results: A total of 118 patients were included in the analysis: 64 and 54 in the pre- and postprotocol groups, respectively. Patients in the preprotocol group were primarily women (53% [34/64]) and had a mean (SD) age of 61 (15.5) years and a mean APACHE II score of 28 (6.0). Patients in the postprotocol group were primarily men (54% [29/54]) and had a mean age of 52 (18.0) years and a mean APACHE II score of 27 (6.4). Implementation of the sepsis protocol resulted in a greater percentage of patients receiving timely antibiotic therapy (ie, within 4.5 hours of refractory shock; 85% [46/54] vs 56% [36/64]; P = 0.001) and adequate fluid resuscitation (72% [39/54] vs 31% [20/64]; P < 0.001) compared with the preprotocol group. Post hoc analysis found significant decreases in the number of vasopressor days (mean [SD], 3.8 [2.7] to 1.4 [1.5]; P < 0.001), ventilator days (9.1 [12.2] to 2.7 [4.0]; P < 0.001), and ICU days (12.3 [12.6] to 4.9 [3.9]; P < 0.001) in the postprotocol group. In-hospital mortality was not significantly different between the groups (survival 46% [28/61] before vs 54% [33/61] after the protocol). Multivariate analysis for predictors of in-hospital mortality identified an interval between shock and empiric antibiotic administration of >4.5 hours (odds ratio [OR] = 5.54; 95% CI, 1.91–16.07; P < 0.002), vasopressor duration in days (OR = 1.27; 95% CI, 1.01–1.59; P = 0.037), APACHE II score (OR = 1.14; 95% CI, 1.05-1.24; P = 0.003), and type of infection (community vs nosocomial, OR = 0.18; 95% CI, 0.05–0.61; P = 0.006) as significant predictors. The 28-day mortality decreased from 61% (39/64) to 33% (18/54) after implementation of the protocol ( P = 0.004). Conclusion: Implementation of a sepsis protocol emphasizing early administration of antibiotic therapy and adequate fluid resuscitation was associated with improved clinical outcomes and lower 28-day mortality in patients with fluid-refractory septic shock at this institution.

Cochrane review: Modes of administration of antibiotics for symptomatic severe urinary tract infections

AbstractBackgroundUrinary tract infection (UTI), worldwide, is a major source of disease in children and adults. As it may have long‐term consequences such as kidney failure and hypertension, it is important to treat patients with UTI adequately. Although standard management of severe UTI usually means intravenous (IV) therapy, at least initially, there are studies showing that oral therapy may also be effective.ObjectivesTo assess whether the mode of administration of antibiotic therapy for severe UTI has an effect on cure rate, reinfection rate and kidney scarring.Search strategyThe Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE and EMBASE were searched. No language restriction was applied. Reference lists of relevant articles and reviews were checked for additional studies and authors of relevant articles/abstracts were contacted for further information.Selection criteriaAll randomised controlled trials (RCTs) comparing different modes of antibiotic application for patients with severe UTI (children and adults) were considered.Data collection and analysisStudy quality was assessed and data extracted. Statistical analyses were performed using the random effects model and the results expressed as risk ratio (RR) for dichotomous outcomes or mean difference (MD) for continuous data with 95% confidence intervals (CI).Main resultsFifteen RCTs (1743 patients) were included. Studies compared oral versus parenteral treatment (1), oral versus switch treatment (initial intravenous (IV) or intramuscular (IM) therapy followed by oral therapy) (5), switch versus parenteral treatment (6) and single dose parenteral followed by oral therapy versus oral (1) or switch therapy (3). There was a variety of short‐term and long‐term outcomes, but no pooled outcomes showed significant differences. Most included studies were small though and there were few outcomes for combination in a meta‐analysis.Authors' conclusionsThere is no evidence suggesting that oral antibiotic therapy is less effective for treatment of severe UTI than parenteral or initial parenteral therapy. The results of this review suggest that the mode of application does not determine therapeutic success.Plain language summaryNo evidence that oral antibiotic therapy is less effective for treating urinary tract infection than intravenous antibioticsSevere urinary tract infection (UTI) is a common infection in adults and children, causing acute disease with a variety of symptoms such as fever and flank pain. This may lead to kidney damage, kidney failure or hypertension. Standard therapy involves antibiotics given at least initially by injection. This review identified 15 studies (1743 participants). The results of this review suggest oral therapy is equally effective in treating UTI and preventing long‐term damage. This might reduce costs but also inconvenience for the patient.

Procalcitonin kinetics within the first days of sepsis: relationship with the appropriateness of antibiotic therapy and the outcome

IntroductionManagement of the early stage of sepsis is a critical issue. As part of it, infection control including appropriate antibiotic therapy administration should be prompt. However, microbiological findings, if any, are generally obtained late during the course of the disease. The potential interest of procalcitonin (PCT) as a way to assess the clinical efficacy of the empirical antibiotic therapy was addressed in the present study.MethodsAn observational cohort study including 180 patients with documented sepsis was conducted in our 15-bed medical intensive care unit (ICU). Procalcitonin measurement was obtained daily over a 4-day period following the onset of sepsis (day 1 (D1) to D4). The PCT time course was analyzed according to the appropriateness of the first-line empirical antibiotic therapy as well as according to the patient outcome.ResultsAppropriate first-line empirical antibiotic therapy (n = 135) was associated with a significantly greater decrease in PCT between D2 and D3 (ΔPCT D2–D3) (-3.9 (35.9) vs. +5.0 (29.7), respectively; P < 0.01). In addition, ΔPCT D2–D3 was found to be an independent predictor of first-line empirical antibiotic therapy appropriateness. In addition, a trend toward a greater rise in PCT between D1 and D2 was observed in patients with inappropriate antibiotics as compared with those with appropriate therapy (+5.2 (47.4) and +1.7 (35.0), respectively; P = 0.20). The D1 PCT level failed to predict outcome, but higher levels were measured in the nonsurvivors (n = 51) when compared with the survivors (n = 121) as early as D3 (40.8 (85.7) and 21.3 (41.0), respectively; P = 0.04). Moreover, PCT kinetics between D2 and D3 were also found to be significantly different, since a decrease ≥ 30% was expected in the survivors (log-rank test, P = 0.04), and was found to be an independent predictor of survival (odds ratio = 2.94; 95% confidence interval 1.22 to 7.09; P = 0.02).ConclusionsIn our study in an ICU, appropriateness of the empirical antibiotic therapy and the overall survival were associated with a greater decline in PCT between D2 and D3. Further studies are needed to assess the utility of the daily monitoring of PCT in addition to clinical evaluation during the early management of sepsis.

Relevance of Helicobacter pylori virulence factors for vaccine development

Helicobacter pylori infection increases the risk for a wide spectrum of clinical outcomes, ranging from peptic ulcer disease to gastric cancer. However, the infection induces gastric and duodenal ulceration or gastric cancer in only a minority of infected subjects because H. pylori strains are genetically diverse and express different virulence factors. Individuals infected with strains that express these virulence factors probably develop severe diseases such as gastric cancer. Nevertheless, the ancient relationship between H. pylori and humans suggests that some strains could be beneficial to human health, which means that generalized administration of antibiotic therapy could eventually cause problems. The development of vaccines based on virulence factors that provide long-term protection is the best strategy for control and/or elimination of pathogenic strains. The different immunization schemes and formulations designed to evaluate the vaccines based on virulence factors in animal models have offered promising results. However, it is necessary to determine whether or not these results can be reproduced in humans. This article reviews recent vaccination studies that explore this possibility: oral vaccines using urease or inactivated whole cells plus LT as adjuvant and urease expressed in Salmonella spp. vectors, as well as a parenteral multicomponent vaccine plus aluminum hydroxide as adjuvant. Although these studies have achieved limited success, they have established support for the development of an effective vaccine against this infection.

Modes of administration of antibiotics for symptomatic severe urinary tract infections.

Urinary tract infection (UTI), worldwide, is a major source of disease in children and adults. As it may have long-term consequences such as kidney failure and hypertension, it is important to treat patients with UTI adequately. Although standard management of severe UTI usually means intravenous (IV) therapy, at least initially, there are studies showing that oral therapy may also be effective. To assess whether the mode of administration of antibiotic therapy for severe UTI has an effect on cure rate, reinfection rate and kidney scarring. The Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE and EMBASE were searched. No language restriction was applied. Reference lists of relevant articles and reviews were checked for additional studies and authors of relevant articles/abstracts were contacted for further information. Date of last search: July 2007. All randomised controlled trials (RCTs) comparing different modes of antibiotic application for patients with severe UTI (children and adults) were considered. Study quality was assessed and data extracted. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or mean difference (WMD) for continuous data with 95% confidence intervals (CI). Fifteen RCTs (1743 patients) were included. Studies compared oral versus parenteral treatment (1), oral versus switch treatment (initial intravenous (IV) or intramuscular (IM) therapy followed by oral therapy) (5), switch versus parenteral treatment (6) and single dose parenteral followed by oral therapy versus oral (1) or switch therapy (3). There was a variety of short-term and long-term outcomes, but no pooled outcomes showed significant differences. Most included studies were small though and there were few outcomes for combination in a meta-analysis. There is no evidence suggesting that oral antibiotic therapy is less effective for treatment of severe UTI than parenteral or initial parenteral therapy. The results of this review suggest that the mode of application does not determine therapeutic success.

Assessing patient preference for two types of elastomeric infusion device

Home administration of antibiotic therapy to cystic fibrosis patients is one of many applications for the use of elastomeric infusion devices. Patient acceptability can significantly affect adherence to complex drug regimens with concordance being a concern in this patient population. While patient acceptance is often cited as a factor in pump selection, patient preference has not been assessed within a particular class of infusion device. The objective of this study was to assess patient preference for one type of elastomeric infusion device (Baxter Intermate--hard-shelled design) or another (Fresenius Kabi Eclipse--soft-shelled design). Twenty-four patients entered the study. 20/24 (83%) patients expressed a preference for the Eclipse, while 4/24 (17%) stated no preference for either device. The Eclipse device was found to be much more favourable in terms of comfort and discreetness. Patient preference should therefore be given significant consideration in order to maximize concordance with drug regimens.

Diagnosis and management of meningococcal disease: the need for centralized care: Figure 1

Meningococcal infection remains a significant health problem in children, with a significant mortality and morbidity. Prompt recognition and aggressive early treatment are the only effective measures against invasive disease. This requires immediate administration of antibiotic therapy, and the recognition and treatment of patients who may have complications of meningococcal infection such as shock, raised intracranial pressure (ICP) or both. Encouragingly, its mortality has fallen in recent years. This is the result of several factors such as the centralization of care of seriously ill children in paediatric intensive care units (PICUs), the establishment of specialized mobile intensive care teams, the development of protocols for the treatment of meningococcal infection, and the dissemination by national bodies and charities of guidance about early recognition and management. We will review the pathophysiology and management of the different presentations of meningococcal disease and examine the possible role of adjunctive therapies.