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Practice guidelines for the treatment of uncomplicated cystitis.

The Infectious Diseases Society of America has published guidelines for the treatment of uncomplicated cystitis. Recommendations are that for healthy, adult, nonpregnant women with bacterial cystitis, 3 days of trimethoprim/ sulfamethoxazole (TMP/SMZ) or trimethoprim alone is standard therapy in those regions where less than 10% to 20% of Escherichia coli that cause such infections is resistant to TMP/SMZ. In those regions where resistance is more than 10% to 20%, the committee recommended using an oral fluoroquinolone for 3 days, and that alternatives such as nitrofurantoin for 7 days or fosfomycin as single-dose therapy need more study. These recommendations were established in the late 1990s as resistance to TMP/SMZ among uropathogens was increasing in the United States, a phenomenon earlier observed in other parts of the world. Clinicians should be alert to patients infected with possibly resistant organisms, eg, patients who have recently been hospitalized or are receiving antibiotics.

Adult↗

Chemotherapy administered using two-route infusion of cisplatin and sodium thiosulfate and intravenous infusion of vinblastine and peplomycin in patients with oral cancer.

The therapeutic effects of neo-adjuvant chemotherapy administered by two-route infusion of cisplatin and its antidote, sodium thiosulfate, and intravenous infusion of vinblastine and peplomycin were studied in 22 patients with previously untreated squamous cell carcinoma of the oral cavity or maxillary sinus. The overall response rate to chemotherapy was 90.9%, with a complete response in 12 patients (54.5%), a partial response in 8 patients (36.4%), and no change in 2 patients (9.1%). Histologic assessment showed a grade V response in 7 patients (31.8%), grade IV in 3 patients (13.6%), grade III in 5 patients (22.7%), grade II in 4 patients (18.2%), and grade I in 3 patients (13.6%). The cumulative 5-year survival rate, including 3 patients who died of another disease, was 72.2%. Leukocytopenia, an important side effect apparently induced by vinblastine, was seen, but no life-threatening complications occurred. Renal toxicity by cisplatin was minimal because of the use of sodium thiosulfate and fosfomycin. These data indicate that this mode of chemotherapy may be more effective for treating head and neck cancer than ordinary chemotherapy, from clinical and histologic standpoints. The high complete-response rate is especially noteworthy. No serious side effects or reductions in treatment period occurred. The results are preliminary and additional studies using a larger patient population are needed.

Adult↗

The mutagenic action of aliphatic epoxides.

The mutagenic action of 45 epoxides was investigates in Luria and Delbrück's fluctuation test with Klebsiella pneumoniae as test organism. In this test, 36 of the 45 epoxides appeared to be mutagenic. The mutagenicity of 1,2-epoxides decreased with increasing length of the carbon chain. The mutagenic activity of compounds with a non-terminal epoxide group appeared to be less than that of substances with a terminal one. Generally 1,2-epoxide compounds with electronegative groups were more mutagenic than 1,2-epoxypropane. Of the diepoxides, 1,2,3,4-diepoxybutane appeared to be more mutagenic than 1,2,7,8-diepoxyoctane, while the ring compounds 1,2,5,6-diepoxycyclooctane was hardly mutagenic. The ring compound 4-vinylcyclohexenedioxide, used in electron microscopy that the antibiotic fosfomycin is among the more potent mutagenic substances investigated in this study.

Epoxy Compounds↗

Microbiologic studies of coagulase-negative staphylococci isolated from patients with nosocomial bacteraemias.

We studied 50 strains of coagulase-negative staphylococci (CNS) isolated from 50 patients with hospital-acquired bacteraemia, identified by prospective surveillance at the University of Virginia Hospital between March 1981 and September 1982. Using the Staph-Ident System for speciation, we found that 37 strains (74%) were Staphylococcus epidermidis, 7 (14%) Staph. hominis, 3 (6%) Staph. haemolyticus and 3 (6%) Staph. warneri. 33 (66%) of the strains produced slime and a higher proportion of the Staph. epidermidis group (75%) than the non-epidermidis group (46%), did so. Minimal inhibitory concentrations (MIC) were determined by a microdilution technique with 20 different antibiotics. There was no difference in geometric mean MICs between slime producers and non-slime producers within either the epidermidis or non-epidermidis group. The most potent antibiotics against Staph. epidermidis (MIC90 mg l-1) were rifampin (0.05), netilmicin (0.05), amikacin (2.9), thienamycin (0.75), teichomycin (0.85), vancomycin (1.0) and nafcillin (0.39). On the other hand strains were resistant to tobramycin (15), moxalactam (50), fosfomycin (greater than 64), and clindamycin (greater than 64). Overall, eight (16%) of the CNS strains were resistant to methicillin, three of which were Staph. haemolyticus. The non-epidermidis strains were more resistant than the Staph. epidermidis strains to most beta-lactam antibiotics. Differences in antibiograms indicate that speciation of CNS may prove useful for clinical and epidemiologic purposes.

Anti-Bacterial Agents↗

Stable Listeria monocytogenes live vaccine candidate strains with graded attenuation on the mouse model.

Metabolic drift (antibiotics resistance) mutations were used to construct stable two (and three) marker vaccine candidate strains of the predominant Listeria monocytogenes serotypes 1/2a and 4b by stepwise selection. Derived from wild-type strains, spontaneous chromosomal streptomycin-resistant clones with their i.p. LD50 elevated from less than or equal to 10(5.0) c.f.u. to approximately 10(6.1) c.f.u. were used in the second step to isolate the rifampicin-resistant mutants with i.p. LD50 values ranging from 10(6.6) to 10(7.4). On i.p. immunization with fully tolerated doses (less than or equal to 1% LD50), these potential vaccine strains were found to protect not less than 95% of the mice against a lethal (approximately 100 LD50) challenge with the homologous wild-type strain. Further elevation of the i.p. LD50 to greater than 10(8.3) c.f.u. by means of a third attenuating fosfomycin-resistance marker resulted in overattenuation and reduced protective capacity.

Animals↗

Sequence of a P-methyltransferase-encoding gene isolated from a bialaphos-producing Streptomyces hygroscopicus.

The nucleotide sequence of the Streptomyces hygroscopicus gene encoding P-methyltransferase, catalyzing the formation of a carbon-phosphorus bond, involved in bialaphos biosynthesis, has been determined. The amino-acid sequence deduced from the nt sequence, shows homology with those of magnesium-protoporphyrin IX monomethyl ester oxidative cyclase (Mg-ProtoMe cyclase) of Rhodobacter capsulatus and the enzyme catalyzing the methylation of the aldehyde carbon of phosphonoacetaldehyde in fosfomycin biosynthesis.

Amino Acid Sequence↗

Cefmetazole (CS-1170), a "new" cephamycin with a decade of clinical experience.

In vitro and in vivo study results were reviewed from cefmetazole, a "new" parenteral cephamycin. Cefmetazole's spectrum of activity was comparable to that of second-generation cephalosporins, which includes clinical coverage of many Enterobacteriaceae, Staphylococcus spp., streptococci, Haemophilus spp., pathogenic Neisseria, Branhamella catarrhalis, and anaerobic bacteria. Cefmetazole was generally more potent (two- to eightfold) than cefoxitin against organisms within their spectrums and was particularly active for staphylococci (MIC90, 2.0 micrograms/ml). Methicillin-resistant S. aureus strains were more susceptible to cefmetazole alone or in combination (fosfomycin) than any other cephamycin. Cefmetazole has demonstrated excellent stability to aerobic and anaerobic organism-produced beta-lactamases. It also inhibits Type I cephalosporinases and, uniquely, some other cephalosporinases produced by the Bacteroides. This superior stability, enzyme interaction, and better penetration into bacterial cells results in a sustained bactericidal effect and a capacity for more infrequent dosing. The cefmetazole serum elimination half-life was 1.5 hr, also justifying use at greater than or equal to 8-hr intervals. Clinical trials in the United States and Japan demonstrated an acceptably high cefmetazole infection cure rate (88% to 100%), especially in direct comparative studies with cefoxitin. Cefmetazole was also proven very effective in minimizing infectious wound morbidity (prophylaxis) using 2 g single- or multidose regimens. Adverse drug reactions were usually minor; in the Japanese surveillance trial (118,318 patients) the rate was only 2.2% (8.8% in United States). Cefmetazole has been extensively and safely used in Japan since 1980.

Bacteria↗

Synergistic effect of CMP/KDO synthase inhibitors with antimicrobial agents on inhibition of production and release of Vero toxin by enterohaemorrhagic Escherichia coli O157:H7.

Synergistic effect of CMP/KDO synthase inhibitors in LPS biosynthesis of Gram-negative bacteria with kanamycin (KM) and fosfomycin (FOM) on the production and release of Vero toxins (VTs) by Escherichia coli O157 was evaluated in vitro. While CMP/KDO synthase inhibitors, KM and FOM showed no inhibitory effect on the production/release of VTs by themselves alone, both KM and FOM showed the remarkable inhibition of VT2 release through synergistic collaboration with CMP:KDO synthase inhibitor.

Anti-Bacterial Agents↗

Detection and antimicrobial susceptibility patterns of Salmonella enterica subsp. arizonae and Proteus spp. associated with gastrointestinal disease in rescued hedgehogs (Erinaceus europaeus).

Western European hedgehogs (Erinaceus europaeus) are frequently admitted to wildlife rehabilitation centres, where infectious diseases may affect recovery and raise One Health concerns. This study aimed to identify bacterial isolates recovered from hedgehog samples submitted for suspected gastrointestinal infection and to characterise their antimicrobial susceptibility profiles. Five bacterial isolates were analysed using the MicroScan WalkAway Plus® system with the Neg-Urine-Combo 98 panel, and the results were interpreted in accordance with EUCAST guidelines. The identified bacteria included one isolate of Salmonella enterica subsp. arizonae, three isolates of Proteus mirabilis and one isolate of Proteus penneri. The Salmonella enterica subsp. arizonae isolate was susceptible to all antimicrobials for which a valid result was obtained. Proteus spp. isolates were susceptible to cefotaxime, nalidixic acid, ciprofloxacin, levofloxacin, norfloxacin, amikacin, gentamicin, tobramycin, aztreonam, cefoxitin, ceftazidime and fosfomycin. However, resistance was observed to amoxicillin-clavulanic acid, ampicillin, ertapenem, meropenem, trimethoprim-sulfamethoxazole, cefuroxime, piperacillin-tazobactam, colistin and nitrofurantoin, with the latter two showing resistance in all Proteus spp. The Proteus penneri isolate displayed the broadest resistance profile, including resistance to several β-lactams, carbapenems. As expected, all Proteus spp. showed intrinsic non-susceptibility to colistin and nitrofurantoin. Although the Salmonella enterica subsp. arizonae isolate was susceptible to the tested agents, Proteus spp. from hedgehog samples may display relevant antimicrobial resistance (AMR) patterns. Therefore, continuous bacteriological monitoring and antimicrobial susceptibility testing are important in wildlife rehabilitation settings to guide treatment decisions and support One Health surveillance.

Antimicrobial resistance↗

Antimicrobial susceptibility patterns, beta-lactamases, and biochemical identification of Yokenella regensburgei strains.

Yokenella regensburgei is an opportunistic human pathogen that phenotypically resembles Hafnia alvei. The susceptibility of 10 Y. regensburgei strains to 75 antimicrobial agents was examined, applying a microdilution procedure in cation-adjusted Mueller-Hinton broth (CAMHB) and IsoSensitest broth (ISB). beta-Lactamases were characterized phenotypically with beta-lactamase activity and induction assays. Genotypically, PCR experiments applying degenerated primer pairs for the detection of AmpC beta-lactamase genes were performed. Examining the phenotypic properties of Yokenella and 76 H. alvei strains with commercial identification systems and conventional tests, a database for an accurate biochemical separation of Y. regensburgei from H. alvei was established. In CAMHB, all tested yokenellae were resistant or at least of intermediate susceptibility to penicillin G, oxacillin, amoxicillin, amoxicillin-clavulanate, cefaclor, cefazoline, loracarbef, cefoxitin, all tested macrolides, lincosamides, streptogramins, ketolides, fusidic acid, glycopeptides, linezolid, and rifampicin. All Yokenella strains were sensitive to several beta-lactams, all tested aminoglycosides, chloramphenicol, folate-pathway inhibitors, fosfomycin, nitrofurantion, quinolones, and tetracyclines. In ISB, the minimum inhibitory concentration (MIC) values of several beta-lactams were one to four MIC doubling dilution steps lower than those found in CAMHB (depending on the beta-lactam). All yokenellae yielded specific amplification products for ampC, and all of these strains expressed beta-lactamases that were strongly inducible. Hydroxyproline amidase, maltosidase, tri-peptidase, proline deaminase, catalase reaction, Voges-Proskauer test, and fermentation of glycerol, melibiose and myo-inositol were suitable parameters to separate Y. regensburgei from H. alvei.

Anti-Bacterial Agents↗

Enterococci spp. isolated from Cuba: species frequency of occurrence and antimicrobial susceptibility profile.

This study investigated the species distribution and antimicrobial resistance among 99 enterococci isolated from hospitalized patients in 12 hospitals in Cuba from October 2000 to September 2001. Species identification was performed by WIDER Automatic System (Francisco Soria Melguizo, Madrid, Spain), and the susceptibility testing was performed by disk diffusion, agar dilution, and E-test methods. Enterococcus faecalis was the most prevalent (85%) species, followed by E. faecium (10%), E. gallinarum (2%), E. casseliflavus (2%), and E. durans-hirae (1%). A higher percentage of resistance to ampicillin (50%), fosfomycin (40%), ciprofloxacin (30%), norfloxacin (20%), and tetracycline (90%) was detected in E. faecium isolates, whereas E. faecalis strains showed higher rates of resistance to erythromycin (52.4%), chloramphenicol (34.5%), rifampicin (62.5%), moxifloxacin (3%), and nitrofurantoin (2.4%). Resistance to glycopeptide was detected in E. faecalis (1.2%) and E. faecium (10%). Thirty-one E. faecalis (37%) and 3 E. faecium (30%) showed a high-level resistance to gentamicin. The results of this work will be very helpful to guide empirical antimicrobial therapy and the implementation of infection control measures in Cuban hospitals.

Drug Resistance, Bacterial↗

Antibiotic-induced apoptosis in human activated peripheral lymphocytes.

Long-term administration of macrolide antibiotics reduced the number of lymphocytes in bronchoalveolar lavage fluid in patients with chronic airway inflammatory disease. To evaluate the inflammatory activity of macrolides, their effect on apoptosis of activated lymphocytes isolated from human peripheral blood was compared with that of other antibiotics. Macrolides, including clarithromycin and azithromycin, at a final concentration of 100 microg/ml accelerated apoptosis of activated lymphocytes, while other antibiotics such as fosfomycin sodium, beta-lactams--ceftazidime, piperacillin sodium and biapenem, and a quinolone, ofloxacin, did not cause significant induction of apoptosis. Our results suggest that 14- or 15-membered ring macrolides are specifically involved in the augmentation of apoptosis of activated lymphocytes, and this may be of value therapeutically for chronic airway diseases.

Annexin A5↗

Urinary tract infection caused by fluoroquinolone- and cephem-resistant Enterobacteriaceae.

In 2001, fluoroquinolone-resistant Escherichia coli isolates emerged in Japan in patients with uncomplicated urinary tract infection (UTI), and accounted for ca. 8% of isolates. This is a worldwide occurrence as reported by the ECO.SENS study. The number of fluoroquinolone- and cephem-resistant Enterobacteriaceae isolates from patients with complicated UTI is increasing. Most cephem-resistant isolates of E. coli, Klebsiella pneumoniae and Proteus mirabilis produce extended-spectrum beta-lactamases (ESBLs). The rates of ESBL-producing Enterobacteriaceae differ between countries but there are ESBL producers in urinary Enterobacteriaceae isolates in most countries. More seriously, most nosocomial ESBL producers are also resistant to non-beta-lactams, such as the fluoroquinolones, fosfomycin and co-trimoxazole. This causes serious problems in the chemotherapy of cystitis.

Ceftizoxime↗

Pulse-field gel electrophoresis typing of methicillin-resistant Staphylococcus aureus strains susceptible to aminoglycosides isolated from 1993 to 2002.

Methicillin-resistant Staphylococcus aureus (MRSA) susceptible strains to aminoglycosides (AS-MRSA) have been increasingly isolated in the Albert Cheneiver Hospital during the past 10 years. The aim of this study was first, to analyse the genotypes and the profiles of resistance to antibiotics and second to compare the AS-MRSA with the MRSA resistant to gentamicin (GR-MRSA) and with MRSA resistant to kanamycin and tobramycin, but susceptible to gentamicin (GS-MRSA), previously studied in our laboratory. All the AS-MRSA consecutively isolated from clinical samples (carriage isolates excluded) from 01/01/1993 to 31/12/2002 (33 isolates) were typed by DNA macrorestriction. Their susceptibilities to other anti-staphylococcal drugs (erythromycin, lincomycin, tetracycline, rifampicin, fusidic acid and fosfomycin) were studied by the French standard disk method. The 33 strains showed a heterogeneous resistance to oxacillin and fell into five phenotypes. The main phenotype (51.5% of the AS-MRSA strains) was susceptible to the six antibiotics studied. DNA macrorestriction defined 24 genotypes (percentage similarity <80%). Among them 16 genotypes contained only one strain each, and none contained more than three isolates. Conversely the comparison with GR-MRSA and GS-MRSA isolated during the same period showed that the strains were not closely linked. The diversity of our isolates showed that it was not an epidemic phenomenon, in contrast to the results of similar studies. Our findings may be explained by the patients coming mostly from different hospital units. This work indicates the need for further studies on the genome, to determine whether AS-MRSA have derived from strains that occurred before aminoglycosides came into clinical use.

Aminoglycosides↗

[Resistance to linezolid in Staphylococcus aureus before its release].

UNLABELLED: Resistance to antibiotics is a global problem in geriatric centres. OBJECTIVE: The aim of this study was to determine the frequency of the resistance to linezolid in Staphylococcus aureus strains before its release in a geriatric centre. METHOD: From 03-01-01 to 03-04-30 linezolid was included in the panel of antibiotics tested in S. aureus strains. The susceptibilities were estimated by the disk diffusion test in routine clinical microbiology practice. RESULTS: A total of 213 strains of S. aureus was analysed. All of them were susceptible to the following antibiotics: linezolid, cotrimoxazol, fosfomycin, and glycopeptides. The meticillin-resistant S. aureus (MRSA) represented 67.1% (60.3-73.3) strains. The resistance to pefloxacin, tobramycin and erythromycin concerned 92.3% (86.3-95.9), 73.4% (65.3-80.3) and 31.5% (24.1-39.8) of MRSA strains respectively. The MRSA strains were less resistant to the following antimicrobial drugs: gentamicin 7.0% (3.6-12.8), fusidic acid 2.1% (0.5-6.5) and rifampicin 1.4% (0.2-5.5). The resistance concerning at the same time gentamicin, pefloxacin and fucidic acid represented 2.1% (0.5-6.5) of SARM strains, rifampicin was not interested. CONCLUSION: Linezolid was effective in vitro in S. aureus strains regardless their susceptibilities in meticillin. According to its effectiveness in vivo, linezolid may be of use for the treatment of infections due to MRSA. However, there has been two reports of resistance of MRSA in clinical infections. The use of linezolid has to follow the instructions and it should be carefully monitored.

Acetamides↗

[Antibiotics resistance of meticilline-resistant Staphylococcus aureus: detection of the first glycopeptides low sensibility strains in Tunisia].

The adaptation of Staphylococcus aureus to the hospital environment led to the acquisition of resistance to all antibiotics available in clinical practice. The aim of this study was to investigate the methicillin-resistant Staphylococcus aureus (MRSA) strains isolated in the F. Bourguiba hospital of Monastir (Tunisia). We determined the antibiotype of all Staphylococcus aureus strains identified. Susceptibility rates to fosfomycin, chloramphenicol, rifampicin and pristinamycin were 7%, 3%, 2% and 0%, respectively. The prevalence of MRSA was 15.5% (96 strains); their susceptible to gentamicin progressively increased. The minimum inhibitory concentration (MICs) of oxacillin, vancomycin and teicoplanin were evaluated for the 96 MRSA strains. We identified two MRSA strains (M4 and M41) showing reduced glycopeptides susceptibility. Further analysis revealed that M4 and M41 harbor the gene encoding the class S and class F proteins specific for the Panton-Valentine Leukocidin (PVL). The mecA gene was detected only in strain M41 which harbors the Staphylococcal Cassette Chromosome (SCCmec) type III. This is the first reported MRSA showing reduced susceptibility to glycopeptides in Tunisia. Regulatory surveillance of susceptibility to antibiotics is needed to reduce the morbidity and the mortality rates as well as societal costs of S. aureus infections.

Acclimatization↗

In vitro susceptibility of field isolates of Francisella tularensis subsp. holarctica recovered in Spain to several antimicrobial agents.

Forty-two recent (1997-1999) Spanish isolates of Francisella tularensis subsp.holarctica were tested in a broth microdilution method for their susceptibilities to 29 antimicrobial agents, including penicillins, cephalosporins, cephamicins, monobactams, penems, aminoglycosides, tetracyclines, macrolides, quinolones, chloramphenicol and fosfomycin. The isolates were resistant to beta-lactam antibiotics and susceptible to chloramphenicol, ciprofloxacin, levofloxacin and norfloxacin.

Animals↗

Epidemiology of urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli.

OBJECTIVES: To describe the epidemiology of urinary tract infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. METHODS: We performed three studies: a trend study (1999 to 2004) to assess the evolution and origin of ESBL-producing E. coli isolates from urine samples; a comparison of the susceptibility patterns of ESBL-producing E. coli and a random sample of non-ESBL-producing E. coli isolated in the same interval, and a retrospective chart review to determine the risk factors for acquisition of, and outcomes from, urinary tract infections caused by ESBL-producing E. coli (n = 61) compared with a random sample of non-ESBL-producing E. coli urinary tract infections (n = 61) from patients attending our institution and matched by temporal occurrence. RESULTS: ESBL-producing E. coli significantly increased from 2 (0.20%) to 89 (5.52%) isolates per year (P value for trend = 0.000). Of the 161 patients with urinary tract infections caused by ESBL-producing E. coli, 100 (62%) were attending ambulatory health centers, and 61 (38%) were attending the hospital. ESBL-producing E. coli showed a significant reduction in the susceptibility to most antimicrobials, although carbapenems and fosfomycin retained significant activity. The chart review study showed that previous treatment with fluoroquinolones (odds ratio 12.98, 95% confidence interval 1.81 to 106.51, P = 0.017) and the presence of a urinary catheter (odds ratio 2.64, 95% confidence interval 1.01 to 6.88, P = 0.047) were independent risk factors associated with infections caused by ESBL-producing E. coli. CONCLUSIONS: ESBL-producing E. coli is a problem of increasing importance. Our study results may help physicians select appropriate antimicrobial therapy in patients suspected of having urinary tract infections caused by ESBL-producing E. coli.

Aged↗