Antimicrobial susceptibility patterns of contemporary pathogens from uncomplicated urinary tract infections isolated in a multicenter Italian survey: possible impact on guidelines

During 2004 four Italian Laboratories assessed the prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in female out-patients. A total of 600 urine samples from individuals aged 18-65 were studied. The overall prevalence of Escherichia coli was 85.3%. Klebsiella pneumoniae, Staphylococcus saprophyticus, Proteus mirabilis, Enterococcus faecalis and other rarer species were far less represented. Determination of the antibiotic susceptibility pattern of the entire collection of E. coli (512 organisms) revealed that among the drugs analyzed ampicillin was the least active molecule with only 62.5% of the strains being inhibited. Amoxicillin-clavulanate and cefuroxime displayed a higher potency (87.7% and 89.2% respectively). Cotrimoxazole inhibited only 70.1% of the uropathogens. The three fluoquinolones tested had comparable activity ranging from 83.0% for ciprofloxacin, to 83.6% for levofloxacin and 84.9% for prulifloxacin, indicating an identical spectrum of cross resistance. Nitrofurantoin (96.7%) and fosfomycin (98.6%) were the most potent drugs. Against the whole collection of uropathogens, only cefuroxime, nitrofurantoin and fosfomycin overcame the threshold of 90% activity, with the fluoroquinolones and amoxicillin-clavulanate suffering from about 15% resistance. The results of this survey strongly support the conclusions of recent Italian guidelines concerning the best empiric treatment of UTI in this country today.     

A survey of antimicrobial drug resistance in respiratory tract pathogens,isolated in a northern Italian teaching hospital between 1990 and 1999

Drug susceptibility test results of respiratory tract pathogens, isolated from patients admitted to the Clinic of Respiratory Diseases of the IRCCS San Matteo Hospital, University of Pavia (Italy) between 1990 and 1999, were retrospectively evaluated. A total of 1366 bacterial isolates were collected, including 499 gram-positive and 867 gram-negative strains. In comparison to methicillin-susceptible Staphylococcus aureus, the methicillin-resistant strains (MRSA) showed high levels of resistance to many selected antibiotics, except for glycopeptides. Resistance rates to beta-lactams were high in both Pseudomonas aeruginosa and in the other gram-negative isolates, while aminoglycoside and ciprofloxacin resistance was less than 20%. Some pathogens became more resistant to selected antimicrobials during the observation period, including staphylococci to methicillin, MRSA to ciprofloxacin, P. aeruginosa isolates to imipenem and ciprofloxacin, and the other gram-negative strains to almost all drugs considered, with the exception of cefotaxime and cotrimoxazole.     

Cefodizime (HR221) versus norfloxacin for treatment of urinary tract infections

Cefodizime is a stable new beta-lactamase cephalosporin chemically related to cefotaxime and with a long half-life. Its clinical efficacy and tolerability were compared with those of norfloxacin in patients with intercurrent urinary tract infections plus chronic liver diseases. Cefodizime (2 g, once a day, i.v.) and norfloxacin (400 mg, twice a day, p.o.) were randomly given to two groups of 20 patients each with urinary tract infections caused by organisms sensitive in vitro to these drugs. Cultures of midstream bladder urine, urinalysis and blood biochemical tests were performed before and after each antibiotic treatment. Clinical resolution was observed in 100% of the patients at the end of the treatments, but bacteriological eradication was obtained in 90% of the patients treated with cefodizime and 85% of those treated with norfloxacin, because of the development in five patients of asymptomatic bacteriuria (superinfections).     

Etiological structure and antibiotic sensitivity of uropathogens in chronic recurrent infection of the lower urinary tract

While acute infections of the lower urinary tract (UT) have been studied in detail and antibiotic therapy of such infections is well known, etiology and choice of antibacterial treatment in recurrent chronic UT infection are not so clear. In our trial we aimed at elucidation of etiological structure of chronic cystitis recurrences by means of microbiological investigation of urine samples from 72 women on extended spectrum of nutrient media. In all the cases urine was infected with both aerobic and non-clostridial anaerobic bacteria. We determined prevalent pathogens and their antibiotic sensitivity and compared them with standard pathogens and their sensitivity in acute lower UT infection. We came to the conclusion that it is necessary to develop new recommendations on antibiotic treatment of recurrent chronic cystitis in women.     

Analysis of the spectrum and antibiotic resistance of uropathogens in outpatients at a tertiary hospital

The objective of this study was to analyse the distribution and antimicrobial resistance of bacterial uropathogens isolated from outpatients at Henan Provincial People’s Hospital. A total of 1419 samples from 823 newly diagnosed and 596 recurrent UTI outpatients culture positive. Escherichia coli was the most common uropathogen. Compared with the recurrent group, the newly diagnosed group had a higher isolation rate of E. coli and Enterobacter cloacae but a lower isolation rate of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. Except for P. aeruginosa, the resistance of Gram-negative bacteria to most antibiotics was less than 30%. All Enterococcus and Staphylococcus spp. were sensitive to linezolid, vancomycin and teicoplanin. Both Gram-negative and -positive bacteria exhibited high susceptibility to fosfomycin. Uropathogens isolated from recurrent outpatients had higher resistance rates than did those isolated from newly diagnosed outpatients. Our study indicated that fosfomycin might be an excellent treatment option for outpatients with UTIs.     

中晚期肿瘤患者导尿管伴随尿路感染的细菌学监测及抗菌药物应用

目的:探讨中晚期肿瘤患者导尿管伴随尿路感染的细菌分布以及抗菌药物的敏感性。方法:选取我院收治的中晚期肿瘤患者留置导尿期间发生尿路感染者183例,取尿液进行细菌培养和药物敏感试验。结果:183例患者共分离得到细菌菌株177株,以革兰阴性菌为主,检出104株,占58.76%,其中大肠埃希菌、克雷伯杆菌分别检出49株（27.68%）和31株（17.51%）;革兰阳性菌检出较少,检出73株,占41.24%,其中金黄色葡萄球菌和表皮葡萄球菌分别检出29株（16.38%）和21株（11.86%）。以大肠埃希菌、克雷伯菌为代表的革兰阴性菌普遍对头孢哌酮/舒巴坦、亚胺培南、哌拉西林/他唑巴坦敏感,敏感性分别为100.00%、97.12%、97.12%,而对氨苄西林、哌拉西林以及头孢唑林的敏感性较低,仅为9.62%、23.08%和27.88%。以金黄色葡萄球菌和表皮葡挞球菌为代表的革兰阳性菌普遍对万古霉素、丁胺卡那敏感性较高,分别达到98.63%、91.78%,而对庆大霉素、红霉素敏感性较低,仅为6.85%、26.03%。结论:引起中晚期肿瘤留置导尿患者发生尿路感染的细菌多样,在早期可根据经验给予氨苄西林和万古霉素联合应用,并根据随后的药物敏感试验对治疗方案及时进行调整,合理应用抗菌药物。     

Trends in the antimicrobial susceptibility of bacterial respiratory tract pathogens--findings of the Alexander Project 1992-1996

The Alexander Project is an ongoing, multicenter surveillance study of the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens with testing undertaken in a central laboratory. During the period 1992-1995, isolates were collected from geographically separate centers in countries of the EU and various states in the USA. In 1996, the project was extended to centers in Mexico, Brazil, Saudi Arabia, South Africa, Hong Kong and other European countries not previously included. Within Europe, France and Spain are established as centers with a high prevalence of both penicillin-intermediate (MIC 0.12-1 mg/l) and resistant (MIC > or = 2 mg/l) strains of Streptococcus pneumoniae, with combined resistance rates in excess of 40% in Toulouse and Barcelona in 1996. Combined rates of intermediate and resistant strains in excess of 10% were found in 1996, the first year of sampling, in Belgium, Switzerland, the Slovak Republic and Hungary. Penicillin resistance has evolved in the USA during the period of study, with rates for combined pneumococcal isolates increasing from 5.6% in 1992 to 16.4% in 1996. Of the new, non-European centers joining the project in 1996, Mexico (intermediate 31.4%, resistant 15.7%) and, in particular, Hong Kong (intermediate 9.1%, resistant 50%) are centers with a high prevalence of penicillin resistance. Macrolide resistance has increased generally among pneumococcal isolates examined during the study period, both in penicillin-susceptible and resistant isolates, and was evident in 16.5% of the 2160 isolates collected during 1996. In four centers (London, UK; Genoa, Italy; Pokfulum, Hong Kong; Leuven, Belgium), macrolide resistance rates exceeded those of combined penicillin-intermediate and resistant strains; in 12/19 centers (63.2%) macrolide resistance was more prevalent than penicillin resistance. In 1996, macrolide resistance was found in excess of 10% of isolates in Poland, Hungary, London, UK, combined USA isolates, the Slovak Republic, Barcelona, Spain, Genoa, Italy, Mexico, Toulouse, France and Pokfulum, Hong Kong. beta-lactamase production was the principal mechanism of resistance found among isolates of Haemophilus influenzae, with rates in 1996 of around 20% or more in France, Belgium and Spain, and in excess of 10% in the UK and the Czech Republic. In the same year in non-European centers, Mexico (25%), Saudi Arabia (27.9%), Hong Kong (37.1%) and the USA (30.4% of combined isolates) had a high prevalence of beta-lactamase production. Isolates of beta-lactamase-negative, ampicillin-resistant H. influenzae were generally very uncommon, with only Barcelona, Spain consistently associated with rates in excess of 1%. beta-lactamase production in Moraxella catarrhalis was observed in over 90% of isolates tested in 1996.     

Antimicrobial resistance among enterobacteriaceae causing uncomplicated urinary tract infections in Mauritius: consequences of past misuse of antibiotics

A study was conducted to determine the nature and antimicrobial susceptibility of uropathogens in Mauritius in order to provide guidance on the empirical treatment of uncomplicated urinary tract infections. The study was based on urine samples sent for bacteriological investigation at the Central Health Laboratory from unhospitalized patients over a 3-month period. Information on organisms isolated in pure growth and their antibiotic susceptibility was collected and analyzed. Entero - bacteriaceae accounted for over 80% of the 260 isolates obtained during the study period, and showed high rates of resistance to ampicillin (80%), co-trimoxazole (50%), nalidixic acid (34%) and ciprofloxacin (26%). Resistance to mecillinam and fosfomycin were only 2% and 0% respectively. The high rate of antimicrobial resistance in Enterobacteriaceae in urine is cause for concern. Fluoroquinolones may not be very reliable for empirical treatment of urinary tract infections in Mauritius. Alternatives such as pivmecillinam and fosfomycin should be considered.     

In vitro susceptibility of community-acquired urinary tract pathogens to commonly used antimicrobial agents in Spain: a comparative multicenter study (2002-2004)

The susceptibility patterns of 2724 uropathogens isolated in 9 Spanish regions during 2002, and 3013 obtained in 2004 were determined. The antibiotics tested were fosfomycin trometamol, amoxicillin, co-amoxiclav, cefixime, cefuroxime-axetil, pipemidic, ceprofloxacin, trimethoprim plus sulphamethoxazole and nitrofurantoin. Escherichia coli was the main pathogen in both studies (73% vs. 68.3%) followed by Proteus mirabilis 7.2% vs. 6.4%) and Klebsiella pneumoniae (5.4% vs. 5.2%). Enteroccocus spp. (4.7% vs. 6.8%), Streptoccocus agalactiae (1.7% vs. 3.1%) and Staphyloccocus saprophyticus (0.7% vs. 1.3%)were the most frequent Gram-positive pathogens. 31.3% of E. coli in 2002 and 32% in 2004 were susceptible to all antibiotics tested. Around 40% of E. coli were resistant to a single agent. 21.6-24.1% were resistant to two antibiotics. 35.4% of first period isolates, and 37.6% of second period ones were resistant to two or more classes of antibiotics. Fosfomycin (2.1- 2.8%) and nitrofurantoin (3.5-5.7%) had the lowest resistance rates for E. coli. Amoxicillin (58.2-58.7%), co-trimoxazole (30.8-33.8%) and ciprofloxacin (22.6-22.7%) showed the highest resistance rates, and their suitability as empiric treatments for UTI should probably be re-evaluated.     

Russian results of the international epidemiological study of clinical aspects and resistance to antimicrobial medicines of cystitis uropathogens in females (ARESC): significance of empiric therapy

A total of 656 female patients from Russia aged between 18 to 65 years with uncomplicated cystitis entered the international ARESC trial, of them 647 were eligible for final analysis. Positive cultural urine tests ( > 10(4) CFU/ml) were in 419 (64.7%) patients, 393 (93.8%) patients had monoinfection. The central laboratory of Genoa (to which the isolated samples were sent) has tested 416 uropathogens from 399 patients. The following pathogens were isolated: E. coli (72.6%), enterococcus (7.0%), Klebsiella pneumoniae (4.6%), Staphylococcus saprophyticus (3.6%), Proteus mirabilis (2.4%) and Staphylococcus aureus (1.7%). E. coli was most sensitive to phosphomycin (99.3%), mecillinam (97.3%), nitrofurantoin (94.7%), ciprofloxacin (87.4%). The lowest sensitivity was to ampicillin (42.1%) and cotrimoxasol (69.4%). As to the whole bacterial spectrum, the highest sensitivity was found to phosphomycin (96.5%), nitrofurantoin (85.6%) and citrofloxacin (82.8%), the less sensitivity--to ampicyllin (44.3%) and co-trimoxasol (70.1%). Phosphomycin, mecillinam (not registered in Russia) and nitrofurantoin showed activity in vitro and can be considered as drugs of choice for empiric therapy of cystitis. Because of high resistance of pathogens, co-trimoxasol (trimetoprim) and fluoroquinalones are not recommended as first-line treatment for uncomplicated cystitis in females.     

Device-related infections in critically ill patients. Part II: Prevention of ventilator-associated pneumonia and urinary tract infections

Device utilization in critically ill patients is responsible for a high risk of complications such as catheter-related bloodstream infections (CRBSI), ventilator-associated pneumonia (VAP) and urinary tract infections (UTI). In this article we will review the current status of data regarding the prevention of VAP and UTI. The results of the more recent (5 years) randomized controlled trials are reviewed and discussed. General recommendations include staff education and use of a surveillance program with a restrictive antibiotic policy. Adequate time must be allowed for hand washing and barrier precautions must always be used during device manipulation. Specific measures for VAP prevention are: 1) use of multi-use, closed-system suction catheters; 2) no routine change of the breathing circuit; 3) lubrication of the cuff of the endotracheal tube (ET) with a water-soluble gel; 4) maintenance of patient in semi-recumbent position to improve chest physiotherapy in intubated patients. Specific measures for UTI prevention include: 1) use of a catheter-valve instead of a standard drainage system; 2) use of a silver-alloy, hydro gel-coated latex urinary catheter instead of uncoated catheters. Biofilm represents a new variable: the capacity of bacteria to organize a biofilm on a device surface can explain the difficulty in preventing and eradicating an infection in a critically ill patient. More clinical trials are needed to verify the efficacy of prevention measures of ICU infections.     

Antibiotic resistance of bacteria associated with community-acquired urinary tract infections in the southern area of the Gaza Strip

The aim of this study was to identify the microorganisms that cause "community-acquired" urinary tract infections among adults and to investigate their resistance to fourteen selected antimicrobial agents. The uropathogens identified in 121 positive midstream urine cultures from the 270 subjects included in this study were Escherichia coli (57.9%), Proteus species (9.9%), Enterobacter species (7.4%), Klebsiella species (6.6%), Pseudomonas species (5.8%), Staphylococcus saprophyticus (5.0%), Enterococcus species (3.3%), Acinetobacter species (2.5%), Citrobacter species (0.8%) and Staphylococcus aureus (0.8%). Isolates were subjected to antimicrobial susceptibility testing and a high proportion of the isolates was found to be resistant to amoxycillin (73.6%), doxycycline (68.6%) and trimethoprim-sulfamethoxazole (66.1%). The most effective drugs against all the isolates were ciprofloxacin (95.9%), amikacin (95.0%) and ceftazidime (94.2%). A high percentage of multiple-drug resistance was also observed for the majority of the isolates.     

Antimicrobial use and resistance among Gram-negative bacilli in an Italian intensive care unit (ICU)

Gram-negative bacilli antimicrobial resistance remains a significant problem for patients in the intensive care unit (ICU). We performed a retrospective analysis of microbiological data and antibiotic consumption over a 4-year period (2000-2003) in an Italian ICU. Pseudomonas aeruginosa and Klebsiella pneumoniae represented approximately 40% of all isolates. The most significant trend in antimicrobial use was an increase in use of 3(rd )generation cephalosporins, imipenem, and ciprofloxacin. A significant trend toward an increase in resistance rates to piperacillin, 3( rd )generation cephalosporins and ciprofloxacin was observed for K. pneumoniae and a positive correlation between resistance and drug-usage was evident for K. pneumoniae and piperacillin, cefotaxime, ceftazidime, cefepime, and ciprofloxacin, but not for piperacillin/tazobactam. No statistically significant correlations were evidenced for P. aeruginosa. Trends in resistances were studied also for Serratia spp and Proteus spp. Isolation rates of extended-spectrum beta-lactamase (ESBL)-producing strains in pathogens studied were high, especially for K. pneumoniae (72%, 160/222) and Proteus spp (41%, 18/43). In conclusion, the study showed high resistance among Gram-negative organisms isolated in the ICU and significant ESBL production. A significant correlation between antibiotic consumption and increasing resistance was evident for K. pneumoniae.     

Effect of indomethacin on N-(4-(5-nitro-2-firyl)-2-thiazolyl)formamide-induced urinary tract carcinogenesis

The effects of indomethacin on the urinary bladder and renalpelvis in rats treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide(FANFT) were studied. Two hundred female Sprague-Dawley ratswere divided into four groups. Group 1 received control dietwithout added chemicals. Group 2 was treated with indomethacin(1 mg/kg per day) in the drinking water throughout the experiment.Groups 3 and 4 received 0.2% FANFT in the diet for seven weeksfollowed by control diet. In addition to FANFT, Group 4 receivedindomethacin, 1 mg/kg per day, for the entire experiment. Therats were sacrificed after 92 weeks. There were no urothelialtumors in the control group, one renal pelvic tumor in the indomethacingroup, 4 tumors in the FANFT group and 10 urothelial tumorsin the FANFT ⁺ indomethacin group. The difference between Groups3 and 4 was statistically significant (P < 0.05). Moderateand severe hyperplasia of the renal pelvic and papillary epitheliumwas found in 15 of 48 rats in Group 2 (indomethacin only) ascompared with 6 of 49 control rats (P < 0.05). Moderate andsevere hyperplasia was equally frequent in Groups 3 and 4 (14and 17 animals in each group, respectively). Twenty-four ratsin Group 2 had mammary tumors as compared to 12 animals in Group1 (P < 0.01). Five of the tumors in Group 2 were adenocarcinomas.There was no difference between the number of mammary tumorsin Groups 3 and 4 (36 and 32 animals in each group, respectively).The results suggest that indomethacin enhances FANFT-inducedurinary tract carcinogenesis. Indomethacin also seems to exertsome tumorigenic activity in the mammary gland.