Epidemiological aspects of antibiotic resistance in hospital microorganisms

A total of 37490 medical histories of patients with "pure" and conditionally "pure" operations were analysed with a purpose of studying the scales of hospital infections in surgical inpatients and the effect of the prophylactic use of antibiotics on the frequency of postoperative complications. It was found that postoperative purulent complications developed in 10-25 per cent of patients. Antibiotics and mainly penicillin and streptomycin were used in the treatment of 75 per cent of patients before, during and after operations. The prophylactic use of the antibiotics in mass operations did not prevent the development of infections. Infiltrates and purulent wounds were more frequent (P less than 0.001) in patients subjected to the antibiotic prophylaxis. This indicates that the use of the antibiotics for preventing possible complications in patients with the "pure" operations and in the majority of patients with the conditionally "pure" operations is not advisable. The strategy of the rational use of antibiotics requires that the staff of the large hospitals should include a chemotherapeutist for defining the tactics of chemotherapy and controlling the use of antibiotics which should promote a decrease in the incidence of hospital infections and in the rate of lethality.     

Cefepime/amikacin in the empirical antibacterial therapy for patients with hemoblastosis of different forms]

The results of the use of cefepime (Maxipime) combination with amikacin vs ceftriaxon combination with amikacin in the treatment of 80 patients with different forms of hemoblastosis are presented. Severe infectious complications in the patients were associated with prolonged and deep neutropenia during inductive or antirelapsing chemotherapy. All the patients in the trial were from the group of high risk of infectious complications with the blood neutrophil count under 100 cells/microliter. The duration of neutropenia averaged 12 days (7 to 15). The average period of the treatment with cefepime and amikacin equaled to 13 days (8 to 16). The treatment with cefepime + amikacin was successful in 38 out of 40 patients (95%). The average period of the treatment with ceftriaxon and amikacin equaled to 14 days (7 to 18). The efficacy of the treatment with ceftriaxon + amikacin was 60% (24 patients out of 40).     

Cefepime treatment efficacy in surgical patients]

Clinical and bacteriologial efficacies of cefepime were studied in the treatment of 20 surgical patients. Intraoperative prophylaxis is with the use of cefepime alone and postoperative prophylaxis with the use of cefepime in combination with some other drugs were applied to 10 patients. No postoperative complications in the group of the 10 patients were stated. The other 10 patients were subjected to intraoperative and postoperative combined prophylaxis with some other antibiotics. In 6 patients of the latter group postoperative complications developed. Obvious clinical advantages of cefepime were demonstrated.     

Sulperazone in the treatment of severe infections in patients with cancer]

For the evaluation of rational sulperazone position in oncological hospital and elaboration of its implementation criteria investigation was performed. The trial included 193 patients (88 patients with injuries, 66 with hospital pneumonia, 39 with urinary track infection). From different clinical material of the patients were isolated 136 straines of Gram-negative bacteria. Suseptibile to sulperazone were 67 per cent of P. aeruginosa, 78-86 per cent of P. vulgaris, Klebsiella and E. coli isolates, 66 [symbol: see text] 60 per cent of Enterobacter and Serratia isolates subsequently. Comparative results of treatment with sulperazone as monotherapy and for combination with aminoglycosides (gentamycin or amicacin) in the case of P. aeruginosa infection demonstrated high sulperazone efficacy not lower than imipenem/cilsatatin and cefepime efficacy in the case of hospital infections treatment at critical care units. Low price of the sulperazone treatment when compared to imipenem/cilastatine is emphasized. Another advantage of sulperazone when compared to cefepime is anaerobic infection treatment--cefepime is administered in combination with metronidazole while sulperazone is used in monotherapy.     

An update on the pharmacoeconomics of antifungal pharmacotherapy

The incidence and severity of invasive fungal infections are on the rise and they pose a risk of significant morbidity and mortality. The cost burden of fungal infections in the United States is high. There are many newer, less toxic antifungal agents to manage these challenging infections; however, these agents also carry a high cost of their own. When considering an antifungal agent for a specific patient, it is important to consider safety, efficacy, and cost, thus making it essential to continually evaluate the antifungal pharmacoeconomic literature to assist in the therapeutic decision-making process for patients with invasive fungal infections. Unfortunately, there is a lack of pharmacoeconomic studies addressing the costs associated with the treatment and prevention of fungal infections. Future large-scale clinical studies should include pharmacoeconomic analyses and end points that encompass all costs associated with antifungal drug use, not solely drug acquisition costs.     

Comparative clinical and epidemiological evaluation of beta-lactam antibiotics in the treatment of intraabdominal infections]

We performed a retrospective, comparative study to evaluate efficacy, safety and economic outcomes of empiric cefoperazone/sulbactam monotherapy compared with the meropenem, imipenem/cilastatine and combination of cefepime plus metroindazol in patients with intra-abdominal infection. A total of 468 patients diagnosed with intra-abdominal abscess, peritonitis, pancreatitis were included in the study (the severity of infection according to scale APACHE II was less than 15). Patients were randomized to be treated with either 500 mg meropemen i.v. every 8 hours or 500 mg imipenem/cilastatine i.v. every 8 hours or 2 g cefepime i.v. every 12 hours plus 500 mg metronidazol twice daily or cefoperazone/sulbactam 2 g daily administered every 12 hours. Overall positive clinical responses (cure or improvement) were achieved at the end of treatment for 87.5 patients in meropenem group, 86.6% in the imipenem/cilastatin group, 85.3% in the cefepime group and 86.8% in cefoperazone/sulbactam group. Total cost of the treatment per 100 patients with intra-abdominal infections for cefoperazone/sulbactam was 1957031 roubles, for combinations of cefepime with metronidazol--2497815 roubles. For carbapenem group cost achieved for meropenem--3085291 rub., for imipenem/cilastatin--2653388 roubles. Rate "cost-effectiveness" in total: 784.47$ for cefepime, and 834.39$ for imipenem/cilastatine, 970.21$ for meropenem and 615.4$ for cefoperazone/sulbactam. The most expensive treatment was considered to be with meropenem and imipenem/cilastatine, main share is determined by initial cost of preparations. Less expensive was treatment by cefoperazone/sulbactam with cefepime and by metronidazol.     

Characteristics and clinical value of extended-spectrum beta-lactamases]

The literature data and the findings of the authors' studies on the role of extended-spectrum bata-lactamases (ESBL) in providing the clinical effect in the treatment of infections due to ESBL-producing organisms were analyzed. The analysis allowed to consider the NCCLS recommendations not sufficiently valid. According to these recommendations the ESBL-producing organisms (among E. coli and Klebsiella spp.) should be regarded as resistant to penicillins, cephalosporins and aztreonam. Susceptibility of 62 Enterobacteriaceae strains that were isolated in 4 therapeutic centres of Tomsk, Nazran and Moscow and proved to be ESBL-producing organisms was tested and it was shown that the 3rd and 4th generation cephalosporins could not be referred to a homogenous group. The same was confirmed by the prospective and retrospective investigations of a multiprofile hospital on the clinical and bacteriological efficacies of the 3rd generation cephalosporins and cefepime in the treatment of hospital-acquired infections due to Enterobacteriaceae strains producing ESBL.     

In vitro activity of cefepime against ESBL-positive clinical strains of gram-negative rods

The aim of this study was to determine an in vitro activity of cefepime against ESBL-positive clinical strains of Gram-negative rods isolated from hospitalized patients. Experiments were performed with 100 ESBL-positive strains of Gram-negative rods isolated from clinical samples in 2004. Strains were identified with the use of automatic ATB Expression system and biochemical ID 32 GN tests (bioMdrieux sa). Extended-spectrum beta-lactamases (ESBLs) were detected by means of disc diffusion methods: the double-disc synergy test (DDST) and the diagnostic disc test (DD, Oxoid Ltd, UK). Susceptibility in vitro of ESBL producers to 4th generation--cefepime was determined with gradient diffusion method Etest (AB Biodisk, Solna, Sweden). MIC value of cefepime was assessed for each strain. Among 100 ESBL-producing strains, 94--belonged to enteric rods and 6--to nonfermentative rods. The greatest number of strains belonged to the species Serratia marcescens (27% of all strains) and next--to the species Enterobacter cloacae (21%). Fourteen strains were susceptible (S) in vitro to cefepime, 12--intermediately susceptible (I) and 74--resistant (R). Application of cefepime in a therapy of infections caused by ESBL-positive strains of Gram-negative rods highly susceptible in vitro to this antibiotic, should be considered.     

The efficacy of cefepime (Maxipime) in the treatment of abdominal sepsis in surgical patients]

The efficacy of cefepime in the treatment of 46 patients operated for general peritonitis of various genesis and severity (APACHE II not greater than 35) was studied. Cefepime was used in a dose of 2 g administered every 12 hours as slow intravenous infusions in 0.9 per cent sodium chloride solution in combination with metronidazole administered intravenously in a dose of 7.5 mg/kg body weight. The treatment course was 4 to 15 days. 45 patients were given diflucan for the prophylaxis of fungal superinfection, 3 patients were given aminoglycoside antibiotics (netilmicin or amikacin) and 2 patients were given vancomycin per os. The favourable clinical effect of the cefepime therapy was stated in 38 patients (82.6 per cent) including 4 out of 10 patients with initial APACHE II > 15. 101 isolates of aerobic gram-negative and gram-positive microbes from 38 patients treated with cefepime in combination with metronidazole were tested to estimate the bacteriological efficacy of the therapy and it was shown that only 5.9 per cent of them was resistant. The pathogen eradication was stated in 84.2 per cent of the patients.     

Clinical and laboratory efficacy of the novel difluoroquinolone Sparflo (sparfloxacin) in therapy of skin and soft tissue infections]

Results of clinical trial of new difluoroquinolone--Sparflo (sparfloxacin, Dr. Reddy's Laboratories Ltd) are presented. Sparfloxacin was used in the treatment of 24 patients at the Department of Wounds and Wounds infections (11 patients) and at the Department of burn wounds (13 patients) of the A.V. Vishnevsky Institute of Surgery. After the treatment with sparfloxacin pathogen eradication was stated in 18 patients, eradication with superinfection--in 13 patients, persistence--in 3 patients. Thus bacteriological efficacy amounted to 87.5 per cent. Pharmacokinetic data demonstrates long-term sparfloxacin circulation in the organism of patients with burns--elimination half-life amounted to 20 hours. Overall after the sparfloxacin use the favourable clinical effect was stated in 100 per cent patients--18 patients (75%) had clinical cure and 6 (25%)--clinical improvement. The drug tolerance was good. It is concluded that clinical and laboratory investigation demonstrated high efficacy of sparfloxacin (Sparflo, Dr. Reddy's Laboratories Ltd) in the treatment of patients with skin and tissue wounds of different localization and genesis, complicated with infections.     

Cefepime (maxipime) in the treatment of severe urinary tract infection]

Comparative susceptibility of microflora isolates from patients with complicated urinary tract infections to cefepime, other cephalosporins, amikacin, ciprofloxacin and ofloxacin was studied. Isolates in the diagnostic titers (5 x 10(4)-5 x 10(8)) from the patients treated with cefepime as etiotropic monotherapy were identified. The treatment course was 7 to 14 days. The daily dose was 1 to 2 g. The clinical and bacteriological efficacies of the cefepime therapy equaled to 93.2 and 85.4% respectively.     

Update on new oral cephalosporins

Only cefprozil and cefpodoxime have been shown to be more effective than comparison agents, and they appear to better tolerated than amoxicillin-containing regimens. The potent Gram-negative activity of cefpodoxime is attractive for selective clinical situations (e.g., in place of a quinolone). However, it has not been tested for the treatment of serious Gram-negative infections. Either of these agents would appear to be preferable to cefaclor in terms of efficacy, safety, and cost. Usage patterns similar to that currently applicable to cefaclor should also be applied to the use of either of these drugs, as they should be reserved for patients who have not responded to first-line therapy or in penicillin-allergic patients who cannot tolerate erythromycin or trimethoprimsulfamethoxazole.     

Antibiotic therapy in children with pertussis]

The data accumulated within the last years required revision of the indications to the use of antibiotics in treatment of pertussis. One of the aims of antibiotic therapy in pertussis was to prevent colonization of B. pertussis in the respiratory tracts. With that end in view the choice of antibiotics should be limited by those, to which the pathogen is the most sensitive i.e. erythromycin, ampicillin and augmentin. Comparative efficacy of erythromycin and ampicillin during the first 2 weeks of the disease was studied in 79 infants at the age not older than 1 year with pertussis and it was shown that erythromycin was advantageous by its therapeutic activity and less side effects. Expedience of the antibiotic therapy during the spastic period for providing a preventive effect on development of bronchopulmonary complications was studied in 201 patients with pertussis. No preventive effect of the antibiotics on development of the bronchopulmonary complications defined by the secondary bacterial flora was recorded. In the group of the patients treated with the antibiotics prophylactically (group 1) the complications were 2.6 times more frequent than in the patients treated with pathogenetic agents alone (group 2). Intrahospital pneumonia developed in 8.9 per cent of the patients in group 1 and in 1.5 per cent of the patients in group 2. Therefore, antibiotics should not be used at the late periods of pertussis for prophylaxis of secondary bacterial complications.     

Ciprofloxacin and antibacterial therapy of respiratory tract infections]

Fluoroquinolones are present considered as an important independent group of chemotherapeutics within the class of quinolones, DNA-gyrase inhibitors characterized by high clinical efficacy and numerous indications, and clinical efficacy and humerous indications, and are known as a serious alternative to other highly efficient broad spectrum antibiotics. Significant clinical experience is accumulated with respect to ciprofloxacin, one of the first agents of the group up to date used clinically. In spite of the negative tendencies in development and distribution of antibiotic resistance, ciprofloxacin remains valid as an alternative drug in the treatment of many infections of various localization. Ciprofloxacin is one of the most useful agents in step-by-step or combined antibacterial therapy. Its us is substantiated by convincing microbiological, pharmacokintic and pharmacoeconomic reasons.     

Pulmonary complications in patients receiving granulocyte transfusions and amphotericin B.

To evaluate the possibility that in febrile granulocytopenic patients amphotericin B given along with granulocyte transfusions could increase the incidence of pulmonary complications, we studied 43 severely granulocytopenic patients during 46 episodes of fever. Granulocytes were administered as part of the clinical protocol to all 19 patients who had clinically or microbiologically documented infection; the other 24 patients were randomly allocated to treatment with granulocytes (13 patients) or without granulocytes (11 patients). In all, 32 patients received granulocyte transfusions during 35 episodes of fever. Pulmonary complications developed in six patients in each of the two randomized groups. The incidence of pulmonary complications was not influenced by the number of granulocyte transfusions or by the number of granulocytes per transfusion. Pulmonary complications were significantly more likely to occur in patients with fungal infections. Amphotericin B was given according to clinical indications; 21 patients in all received it. Survival was significantly poorer in patients with pulmonary complications, but the administration of amphotericin B was not related either to survival or to the incidence of pulmonary complications. We conclude that pulmonary complications and poor prognosis are related to underlying pulmonary fungal infection and not to any interaction between amphotericin B and granulocyte transfusions.     

Use of cimetidine in hospital patients.

The use of cimetidine in 137 patients in a large Canadian teaching hospital was assessed prospectively. About 80% of the patients received the drug for treatment and 20% received it for prophylaxis. All of the prophylactic indications as well as some of the treatment indications have not been approved by the health protection branch of the Department of National Health and Welfare, nor do most have adequate literature documentation. The duration of therapy varied from less than 3 days to more than 2 months. The average cost of cimetidine therapy was $40.71. The dosage was not adjusted in over 50% of the patients in whom impairment of renal function was serious enough to warrant consideration of a dosage reduction. Approximately half of the patients received concurrent antacid therapy. Although cimetidine is relatively safe, its use in this institution was less than optimal.     

腹腔镜与阴式子宫肌瘤剔除术临床疗效比较

目的观察比较腹腔镜与阴式子宫肌瘤剔除术的临床疗效。方法符合手术指征的90例子宫肌瘤患者分为腹腔镜组和阴式组（每组45例）,比较疗效。结果二组疗效相似,且术后无并发症发生,住院时问相当。阴式组手术时间、术中出血量、术后排气时间、住院费用明显低于腹腔镜组。结论与腹腔镜手术相比,经阴道手术直视下操作精确、快捷,价格低廉,适应症宽。但由于阴道空间狭窄,易损伤邻近脏器。临床应根据不同情况选择不同的手术方法,达到满意的治疗效果。     

Prophylaxis and treatment of bacterial infections: do we need new strategies?

Bacterial infections in patients with hematologic malignancies still represent a severe and life-treating problem. Several observational studies during the last decade have revealed that neutropenic patients with fever are a heterogeneous population with various differences regarding response to initial therapy, development of serious complications and mortality. The role of neutropenia as main risk factor for infections in hematologic patients and the definition of different level of risk related to neutrophils count and duration of neutropenia have been extensively studied and different categories of patients based on the risk of infection, mostly the condition of neutropenia, have been clearly defined. The strategies on antimicrobial therapy and supportive care in hematologic patients need to be continuously assessed, in fact new conditions favouring the occurrence of infectious complications in patients with hematologic malignancies have progressively emerged. The use of oral prophylactic antibiotics in neutropenic cancer patients is still a matter of debate. Before 2005, several trials showed how the prevention of infection can be extremely important in this setting of patients but none was conclusive. In 2005 two meta-analysis and two large randomized clinical trials gave new evidence that antibacterial prophylaxis can reduce in neutropenic patients several important outcomes including mortality. The use of the empiric antibacterial therapy represents the cornerstone of the antimicrobial strategies in the febrile neutropenic patients leading, over the span of 20 years, to a dramatic decrease of deaths: Actually beta-lactam monotherapy is commonly used for the empiric treatment of febrile neutropenia. Recently, large randomized clinical trials and meta-analysis showed that the addition of an aminoglycoside and/or a glycopeptides results in a more favourable outcome only in selected severe infections. The use of antibiotics should be prudent and safe also in neutropenic hematologic patients to prevent emergence of microbial resistance, to save costs, to reduce toxicity. For this reasons, according to the evidence, antibacterial prophylaxis should be restricted to high risk hematologic patients and empiric parenteral antibiotic monotherapy should be recommended in case of febrile neutropenia limiting the use of amynoglicosides and glycopeptides. In the next future, a major effort should be made to state in hematologic patients new risk factors which could more accurately define subgroups for targeted anti-infective strategies.     

Quality of use of parenteral metronidazole therapy in a teaching hospital

The recent release, relatively high cost and potential adverse effects of parenterally administered metronidazole prompted a quality-of-use audit at a 1000-bed teaching hospital. Ninety-two courses of treatment in 81 inpatients during a 6-week period were studied. Appropriateness of therapy was assessed on the basis of published indications. Parenterally administered metronidazole was prescribed primarily in anaerobic and anaerobic-aerobic infections. It was used as frequently for prophylaxis as for therapy. Surgical services accounted for 95% of the treatment courses. Inappropriate use was noted in 27 (29%) of the courses: agents other than parenterally administered metronidazole were indicated in 12 (13%), while the dose, dosing interval or duration of treatment was suboptimal in 15 (16%). Substantial savings would be achieved if oral or rectal metronidazole therapy were substituted for intravenous therapy for perioperative prophylaxis in elective colorectal surgery. Written justification for use and automatic stop orders are recommended to improve the cost effectiveness of both prophylactic and therapeutic use of selected antimicrobial agents.