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.     

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.     

Enterobacterial sensitivity to beta-lactam antibiotics]

The susceptibility to betalactams of 868 enteric bacteria isolated from the patients at the hospital was studied. The isolated pathogens included: E. coli (549), Klebsiella sp. (195), Serratia sp. (124). Ampicillin and cefazoline demonstrated the lowest activity. Cefotaxime, ceftazidime and imipenem were active against 90 per cent of isolates. Among E. coli isolates the susceptibility to the above mentioned drugs was the following: 95.1, 96.9, 99.3 per cent, among Klebsiella sp.--89.7, 88.7, 97.9 per cent, among Proteus sp.--89.5, 90.3, 91.9 per cent respectively. Thus cefotaxime may be used in antibacterial empiric therapy if Pseudomonas aeruginosa infection is excluded.     

Use of pefloxacin in the treatment of patients with purulent wounds of soft tissues]

Pefloxacin was used in the treatment of 25 patients with wound infection in a dose of 400 mg orally twice a day for 10-12 days. As the monotherapy it was applied to 15 patients. 7 patients with clinical signs of non-clostridial anaerobic infection were treated with pefloxacin in combination with intravenous metronidazole. Pefloxacin was highly efficient in 96 per cent of the cases with extensive posttraumatic purulent wounds with and without bone affection, acute purulent wounds of the soft tissue, purulent wounds of the soft tissues in diabetic patients, trophic or decubitus ulcer. 266 clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Proteus mirabilis, Enterobacter spp. and Acinetobacter spp, were tested and 75 to 100 per cent of them was shown to be susceptible to pefloxacin and ciprofloxacin. At the same time the isolates of Pseudomonas aeruginosa and Klebsiella spp. were more susceptible to ciprofloxacin. The pathogen eradication and eradication with superinfection in the cases treated with pefloxacin amounted to 92 per cent. The drug tolerance was good. No clinically significant adverse events were recorded.     

3-Year experience of use of cefepime (Maxipime) for the treatment of hospital infections in a specialized surgical hospital]

Microbiological and clinical monitoring for 3 years (from 2001 to 2003) confirmed high clinical and microbiological efficacy of cefepime (Maxipime, Bristol-Myers-Squibb) in the treatment of infectious complications in patients with solid tumors in an oncologic hospital. It should be noted, however, that high efficacy of cefepime and wide ranges of the indications to its use do not allow to consider it as an agent for the treatment of all possible complications in such patients. The drug is not active against enterococci, not always clinically sufficiently effective in the treatment of Pseudomonas aeruginosa infections, it is impossible to use cefepime in monotherapy of suspected anaerobic infections. Therefore, widespread uncontrolled use of cefepime should be prohibited. It should be prescribed strictly by the indications with the account of the pathogen susceptibility, the infection severity and the recommended doses and regimens. The use of cefepime is undoubtedly valid when other antimicrobials fail or when empirical antimicrobial therapy of severe cases is required, including those under intensive care.     

The comparative activity of cefepime and other current antibiotics against microorganisms isolated from patients in pediatric intensive therapy units]

Comparative activity of cefepime, ceftazidime, ceftriaxone, ciprofloxacin, imipenem and piperacillin/tazobactam against isolates from patients of pediatric intensive care units within October-December 1998 was studied. The isolates were identified with the Walkaway-40 System. The antibiotic susceptibility was evaluated by the E-test on the Mueller-Hinton II agar. The data were interpreted in accordance with the NCCLS. The number of the isolates totaled 100. Among them not more than 10 to 12 strains belonged to the same species. 92 per cent of the isolates was susceptible to cefepime and 70 to 75 per cent of the isolates were susceptible to the third generation cephalosporins. Piperacillin/tazobactam proved to be highly susceptible, the number of the isolates resistant and moderately resistant to it being 6 and 1 per cent respectively. The results showed that cefepime was intermediate between the third generation cephalosporins and carbapenems.     

Microbiological monitoring for the causative agents of nosocomial infections (exemplified by resuscitation and intensive therapy units)]

More than 900 isolates from at least 1500 patients were tested within 1996-1998. Gram-negative organisms were the main pathogens isolated from patients with different forms of nosocomial complications such as late pneumonia, associated with artificial ventilation of the lungs, and various secondary wound or urinary tract infections. The prevalence of Pseudomonas aeruginosa was stated. Antibioticograms showed that the most active drugs were imipenem (more than 90 per cent of the susceptible isolates) and ticarcillin/clavulanate (48-58 per cent of the susceptible isolates). The activity of ticarcillin/clavulanate (Timentin) was practically the same as that of imipenem against 21 strains of P.aeruginosa isolated from the blood and cerebrospinal fluid of 21 patients with sepsis and 3 patients with secondary purulent meningitis.     

Antibiotic sensitivity of pneumonia pathogens in newborns and problems of antibacterial therapy of the pathologic process]

The results of the bacteriological investigation of the secretion from the trachea, large bronchi and fauces of 36 newborns (including 27 preterms) with severe pneumonia were analyzed. 20 of them were born of women with complicating somatic, obstetric and gynecologic histories: candidiasis, herpes genitalis, chronic endometritis, adnexitis or chronic pyelonephritis that could be the risk of the fetus intranatal infection. During the acute period of pneumonia in the newborns within the first 4-8 days of life mainly Pseudomonas aeruginosa was isolated (51.3 per cent), Staphylococcus epidermidis, S. haemolyticus and Enterococcus faecalis were less frequent (18.9, 8.1 and 5.4 per cent, respectively). Klebsiella pneumoniae, Streptococcus anhaemolyticus and other organisms were extremely rare. On the whole the gramnegative microflora predominated. The study of the antibiotic susceptibility showed that the majority of the P. aeruginosa isolates were susceptible to amikacin and polymyxin B, the isolates susceptible to ceftazidime were less frequent, 20-25 per cent of the isolates were susceptible to ciprofloxacin, cefoperazone and imipenem and practically no isolates were susceptible to gentamicin. The S.epidermidis isolates were susceptible to rifampicin and vancomycin and in rare cases to fusidin and amikacin and resistant to oxacillin. When the treatment course was more than 15 days, the isolates proved to be susceptible to 1/3 of the presently available antibiotics. Because of the host low protective forces, peculiarities of the infection pathways and high frequency of the resistant strains it is valid to include netilmicin, imipenem, cefoperazone and ceftriaxone to the complex therapy of the newborns along with the substitution immunotherapy.     

Resistance of urinary tract infection pathogens and choice of antibacterial therapy in pediatric urologic practice]

The data on antibiotic resistance of the main uropathogens isolated from patients with urinary tract infection in an urologic department (319 isolates) and outpatient and diagnostic units (360 isolates) are presented. It was shown that by the antibiotic resistance the Escherichia coli isolates from the urologic department patients and outpatients did not practically differ: 44.1 and 47.8% of the isolates were resistant to ampicillin, 26.7 and 23.4% were resistant to amoxycillin/clavulanate, 28.9 and 24.9% were resistant to co-trimoxazole and 26.5% was resistance to cefuroxime (outpatients). The basic differences referred to Pseudomonas aeruginosa: resistance to ceftazidime in 38.5% of the isolates and resistance to gentamicin in 36.2% of the isolates. The activity against P. aeruginosa could be arranged as follows in the decreasing order: amikacin = meropenem > imipenem > cefepime = cefoperazone/sulbactam > gentamicin = ceftazidime. Resistance of P. aeruginosa to fluoroquinolones (ciprofloxacin and levofloxacin) remained low (7.4 and 8.0% respectively). No ampicillin resistance was revealed in the isolates of Enterococcus faecalis.     

Cefepime in the treatment of infection in neutropenic patients]

Cefepime, a fourth-generation cephalosporin, was used in the treatment of 11 febrile episodes in 8 patients with profound neutropenia. The patients were neutropenic because of high-dose chemotherapy with stem-cell rescue or second-line salvage chemotherapy for malignant lymphomas (5 patients) or solid tumors (3 patients). The median duration of grade-IV neutropenia (according to the WHO classification) was 11 days (7 to 14). Cefepime was used as the monotherapy in a dose of 2 g thrice daily. Disappearance of the infection signs was recorded in 8 episodes (73 per cent). In 3 episodes (23 per cent) cefepime was replaced by another drug. The tolerability of cefepime was good and no adverse events were observed with the exception of 1 event of an allergic reaction.     

Efficacy of meropenem in the treatment of severe complicated urinary tract infections]

The clinical and bacteriological efficacies of meropenem in the treatment of 12 patients with urinary tract infection were studied. In 8 patients the drug was administered intravenously in a dose of 1 g every 8 hours and in 4 patients with the creatinine clearance below 50 ml/min it was administered in a dose of 1 g every 12 hours (the treatment course of 7 to 10 days). Meropenem was used in the monotherapy. Severe complicated urinary tract infections were mainly observed in the patients with long-term urolithiasis, subjected to repeated surgical interventions and isolating as a rule polyresistant strains of Pseudomonas aeruginosa and E.agglomerans as the pyelonephritis pathogens at a titre of 5 x 10(5)-5 x 10(8) microbial cells per 1 ml of the urine susceptible to meropenem in 80 to 96 per cent of the cases. The clinical efficacy of the drug was stated in all the patients while the bacteriological efficacy amounted to 88.9 per cent.     

奇异变形杆菌耐药性及亚胺培南不敏感株感染的临床特点研究

目的研究奇异变形杆菌的临床分布和耐药情况、亚胺培南不敏感奇异变形杆菌感染的临床特点。方法分析浙江大学医学院附属第一医院2013年1月至2013年12月分离的非重复奇异变形杆菌的药物敏感性、临床分布,回顾性分析亚胺培南不敏感奇异变形杆菌感染患者的临床资料、治疗及预后情况。结果2013年该院共分离107株奇异变形杆菌,以分离自尿液最多,其次为痰液;来源最多的是外科病房和重症监护病房。体外药敏显示：奇异变形杆菌对美罗培南、厄他培南、头孢吡肟、氨曲南、哌拉西林/他唑巴坦、头孢他啶、头孢哌酮/舒巴坦、阿米卡星等抗菌药物敏感性良好,敏感率达85%以上;对亚胺培南敏感率为80.4%;对头孢呋辛、环丙沙星、氨苄西林、头孢曲松、庆大霉素耐药率较高,超过30%;对呋喃妥因耐药率为99%。其中21株亚胺培南不敏感奇异变形杆菌对包括美罗培南、厄他培南在内的其他各类抗菌药物耐药率与亚胺培南敏感株基本相仿。亚胺培南不敏感奇异变形杆菌引起院内获得性感染主要发生在入住ICU、外科术后、广谱抗菌药物使用后、留置各类置管和梗阻性尿路疾病的患者,可引起泌尿系统、皮肤创面、腹腔、血流、生殖道等部位感染,表现为全身炎症反应及局部感染症状。选择敏感抗菌药物治疗后该部分患者预后良好。结论奇异变形杆菌对三、四代头孢菌素,β-内酰胺酶抑制剂合剂等抗生素敏感性良好。亚胺培南不敏感奇异变形杆菌对其他碳青酶烯类抗生素仍保持较高的敏感性。亚胺培南不敏感奇异变形杆菌所引起院内获得性感染主要发生在入住ICU、外科术后、广谱抗菌药物使用后、留置各类置管和梗阻性尿路疾病的患者,预后良好。     

Monitoring of uropathogens and their susceptibility to antibiotics]

Samples of urine collected from patients with complicated urology infection and hospitalized to the Moscow Region Research Clinical Institute in 1986, 1991, 1995 and 1999 were analysed. Of 11,444 samples examined, bacteriuria was estimated in 7143 samples. 9786 strains (29 genus) of bacteria were isolated--56.9 per cent as mono culture and 43.1 per cent as associations. Susceptibility to 21 antibiotic was determined by disk diffusion method for 1607 strains; beta-lactamase production was determined in 198 strains, MIC was determined for 41 antibiotics. Gram-negative rods relative amount among pathogens decreased substantially (84.7 per cent in 1986 against 61.6 per cent in 1999), particularly Enterobacteriaceae (74.7 per cent in 1986 against 41.4 per cent in 1999). Nonfermenting Gram-negative rods (NFGNR) relative amount increased (10.8 per cent against 19.2 per cent), along with Gram-positive cocci (19.8 per cent against 64.2 per cent), particularly coagulasenegative staphylococci (CNS) (10.8 per cent against 35.9 per cent) and enterococci (5 per cent against 16.5 per cent) and candida and fungi (0.5 per cent in 1986 against 15.9 per cent in 1999). At the period 1986-1999 the main pathogens in urology infection were E. coli, Enterobacter spp., NFGNR (including P. aeruginosa), Staphylococcus, CNS, Enterococcus spp. The problem pathogens for urological department were the following: E. coli, Klebsiella spp., Enterobacter spp., Proteus spp., NFGNR including P. aeruginosa, CNS, Enterococcus spp., candida and fungi. At the period 1991-1997 Gram-negative pathogens susceptibility to amikacin, ofloxacin, ciprofloxacin, imipenem, ceftazidime, cefotaxime was not changed in general, Gram-positive cocci (staphylococci and enterococci) retained the same susceptibility to vancomicin, cefamandol and amoxyclave. Staphylococci were also susceptible to amikacin, imipenem, rifampicin, oxacillin, ciprofloxacin, and ofloxacin. Production of beta-lactamase was registered for 38.7 per cent of CNS, 26.5 per cent of E. coli, 38.5 per cent of K. pneumoniae, 25 per cent of P. mirabilis and 55.6 per cent of P. aeruginosa strains.     

铜绿假单胞菌的院内感染分布及耐药性的调查

目的了解铜绿假单胞菌（PA）在医院内感染的分布特点及其耐药性,指导临床合理用药,降低医院感染率。方法回顾分析2005年1月至2008年11月我院临床分离的铜绿假单胞菌152株,按WHO推荐的NC-CLS标准方法（K—B法）进行药敏试验,分析菌株的临床分布特征及体外药敏结果。结果铜绿假单胞菌在临床上主要以呼吸道感染为主。在17种临床常用抗生素中,多表现为多重耐药。美洛培南、亚胺培南及左旋氧氟沙星抗PA效果最好,耐药率分别只有14．47％、14．47和5．26％。结论多重耐药铜绿假单胞菌在临床广泛存在,应当根据临床体外药敏结果合理选择抗菌药物进行治疗,以取得良好临床效果并减少耐药菌产生;同时规范院内感染控制措施,减少耐药菌株的播散。     

Effect of tannin extract against Pseudomonas aeruginosa producing metallo beta-lactamase

Carbapenems are the most potent beta-lactam agents with a broad-spectrum activity against Gram-negative and Gram-positive bacteria. They are stable in the presence of penicillinases and cephalosporinases. This study was focused on frequency of metallo beta- lactamase (MBL) among Pesudomonas aeruginosa strains isolated in patients with urinary tract infection, effect of tannin against PA positive strains which produced blaVIM or blaIMP and both of these genes (Species). Detection of MBL was performed by phonotypic and genotypic methods. Tannin extract was tested against P. aeruginosa producing MBL. During the study period, 240 P. aeruginosa isolates were identified. Among them 64 (26.6 percent) isolates were imipenem non-susceptible and confirmed by imipenem/EDTA. Our results revealed that the growth of blaVIM positive P. aeruginosa inhibited at 15 microg/ml concentration. The experiment repeated for blaIMP-positive P. aeruginosa and P. aeruginosa which harbored blaIMP and blaVIM, the results showed 35 microg/ml was the best concentration for inhibition of P. aeruginosa-positive blaIMP and also P. aeruginosa blaIMP and blaVIM. In conclusion, tannin was effective against P. aeruginosa producing blaVIM and blaIMP and both of them so it can be substituted with common antibiotics. The result showed significantly P. aeruginosa-harbored blaIMP was more responsible for imipenem resistance than P. aeruginosa-positive blaVIM. Interestingly, tannin was more effective against MBL-P. aeruginosa in comparison with current antibiotics.     

Prevalence of metallo-beta-lactamase among Pseudomonas aeruginosa and Acinetobacter baumannii in a Korean university hospital and comparison of screening methods for detecting metallo-beta-lactamase

To identify the metallo-beta-lactamases (MBLs) prevalent in Korea, a total of 130 clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii (99 P. aeruginosa and 31 A. baumannii) with a reduced susceptibility to imipenem (IPM) and/or ceftazidime (CAZ) was subjected to PCR analyses with primers specific to bla(IMP-1), bla(VIM-1), and bla(VIM-2). In addition, inhibitor-potentiated disk diffusion methods (IPD) using two kinds of substrate-inhibitor combinations (ceftazidime-2-mercaptopropionic acid (2MPA) and imipenem-EDTA) were investigated. Thirty-three isolates (29 P. aeruginosa and 4 A. baumannii) carried bla(VIM-2) and two P. aeruginosa isolates harbored bla(IMP-1). The enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) pattern revealed that many of the VIM-2-producing P. aeruginosa isolates were clonally related, whereas the A. baumannii isolates were diverse. The inhibitor-potentiated disk diffusion test using imipenem-EDTA was highly sensitive and specific for detecting the VIM-2 producer. These results suggest that VIM-2 is an important MBL in P. aeruginosa and A. baumannii in the Korean hospital of this study and that the IMP-1-producing P. aeruginosa has also emerged. Screening for MBLs and strict infection control for these isolates will contribute to prevent further spread of resistance.     

Antibiotic sensitivity and pathogenetic factors of hospital strains of Pseudomonas aeruginosa isolated from patients treated in a resuscitation unit]

Strains of Pseudomonas aeruginosa were isolated from patients treated in the Centre of Thermal Affections in 1985-1989. It was shown that 72.9, 59.3, 33.8 and 54.2 per cent of the isolates were sensitive to cefotaxime, tobramycin, gentamicin and polymyxin, respectively. The study of pathogenicity factors of the isolates revealed that 83 per cent of the strains produced thermolabile enterotoxin, 79.6 per cent of the strains had adhesive activity and 71.1 per cent of the strains produced hemolysin. The study detected combinations of various pathogenicity factors. 42.3 per cent of the isolates had both adhesive and enterotoxigenic properties. Adhesiveness and hemolytic activity were shown by 13.5 per cent of the strains. 16.9 per cent of the strains produced both enterotoxin and hemolysin. Adhesive activity, enterotoxigenicity and hemolysin production were observed in 6.7 per cent of the strains. It was noted that the strains of P. aeruginosa resistant to polymyxin mainly produced enterotoxin (18.6 per cent) and those resistant to cefotaxime had adhesive activity (34.0 per cent).     

The serological characteristics of the O antigens of Pseudomonas aeruginosa isolated from patients with a Pseudomonas infection during immunotherapy]

Serologic characteristics of P. aeruginosa O-antigens isolated from patients with P. aeruginosa infection were studied over the course of treatment with anti-P. aeruginosa sheep immunoglobulin. The preparation was used in 54 patients with nongeneralized forms of P. aeruginosa infection (infected wounds, pleural empyema) externally or intraperitoneally. From the clinical material collected from the patients a total of 54 P. aeruginosa strains were isolated. Serologic typing of the isolated strains with factor or group diagnostic agglutinating sera has revealed the O-group composition of the isolated strains; 66% of them were classified with O-groups 2,3, and 6. Serologic variants of the strains isolated from patients proved to be stable over the course of the disease immunotherapy. Analysis of the results of bacteriologic control of immunotherapy. efficacy and the clinical data has demonstrated the efficacy of immunotherapy in 61.1% of cases and its partial effect in 20.4% of cases of P. aeruginosa infection.     

The clinical efficacy of ticarcillin/clavulanate in severe pneumonia]

Efficacy of ticarcillin/clavulanate was studied in the treatment of 11 patients with severe community- and hospital-acquired pneumonia in an open controlled trial. The drug was administered in a dose of 3.1 g every 4 or 6 hours depending on the infection severity. When pneumonia was due to Pseudomonas aeruginosa, amikacin was additionally used. The positive clinical effect of ticarcillin/clavulanate was stated in 73 per cent of the patients. The pathogen eradication was stated in all the patients. However, in 2 cases superinfection due to P.aeruginosa developed. Mild adverse effects were observed in 2 cases. It is concluded that ticarcillin/clavulanate is highly efficient in the treatment of patients with severe or complicated pneumonia. In cases with ventilator-associated pneumonia it is advisable to use ticarcillin/clavulanate in combination with an aminoglycoside.     

Efficacy and safety of cefepime in the treatment of bronchopulmonary disease exacerbation in pediatric patients with mucoviscidosis]

Clinicobacteriological effect of cefepime (in combination with amikacin) was studies in 25 pediatric patients of the age of 7 to 17 years with a mixed form of mucoviscidosis at the stage of the bronchopulmonary infection exacerbation. The basic pathogens isolated from the sputum were: Pseudomonas aeruginosa sm., P. aeruginosa muc. (67.5%) and Staphylococcus aureus (29.1%). The 2-week treatment course resulted in a marked clinical effect with improvement of the lung functional indices and eradication of the majority of the S. aureus strains (81.2%) and half of the P. aeruginosa strains (49.6%). The only side effect was moderate diarrhea not requiring discontinuation of the drug use.