Ambrisentan improves exercise capacity and symptoms in patients with portopulmonary hypertension.

INTRODUCTION: Ambrisentan, a selective endothelin receptor antagonist has been approved in several countries for pulmonary arterial hypertension. No data have been published on the efficacy of ambrisentan on improvement of exercise capacity in patients with portopulmonary hypertension (PoPH). PATIENTS AND METHODS: We retrospectively analyzed the safety and efficacy of ambrisentan in patients with PoPH in four German university hospitals. RESULTS: 14 patients with moderate to severe PoPH were included. The median follow-up was 16 months (IQR, 12 - 21). 6 minute walk tests after 6 and 12 months improved from 376 meters (IQR, 207 - 440) at baseline to 415 meters (IQR, 393 - 475; p = 0.011) and 413 meters (IQR, 362 - 473, p = 0.005), respectively. WHO- functional class after 1 year of therapy with ambrisentan also improved significantly (p = 0.014). No significant changes in blood gas analysis and liver function tests (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and international normalized ratio) during therapy with ambrisentan were detectable. CONCLUSIONS: The present study demonstrates significant improvement of exercise capacity and clinical symptoms without relevant safety concerns during ambrisentan treatment in patients with PoPH.

Concordant genotype of upper and lower airways P aeruginosa and S aureus isolates in cystic fibrosis.

RATIONALE: Lower airway (LAW) infection with Pseudomonas aeruginosa and Staphylococcus aureus is the leading cause of morbidity in cystic fibrosis (CF). The upper airways (UAW) were shown to be a gateway for acquisition of opportunistic bacteria and to act as a reservoir for them. Therefore, tools for UAW assessment within CF routine care require evaluation. OBJECTIVES: The aims of the study were non-invasive assessment of UAW and LAW microbial colonisation, and genotyping of P aeruginosa and S aureus strains from both segments. METHODS: 182 patients with CF were evaluated (age 0.4-68 years, median 17 years). LAW specimens were preferably sampled as expectorated sputum and UAW specimens by nasal lavage. P aeruginosa and S aureus isolates were typed by informative single nucleotide polymorphisms (SNPs) or by spa typing, respectively. RESULTS: Of the typable S aureus and P aeruginosa isolates from concomitant UAW- and LAW-positive specimens, 31 of 36 patients were carrying identical S aureus spa types and 23 of 24 patients identical P aeruginosa SNP genotypes in both compartments. Detection of S aureus or P aeruginosa in LAW specimens was associated with a 15- or 88-fold higher likelihood also to identify S aureus or P aeruginosa in a UAW specimen from the same patient. CONCLUSIONS: The presence of identical genotypes in UAW and LAW suggests that the UAW play a role as a reservoir of S aureus and P aeruginosa in CF. Nasal lavage appears to be suitable for non-invasive UAW sampling, but further longitudinal analyses and comparison with invasive methods are required. While UAW bacterial colonisation is typically not assessed in regular CF care, the data challenge the need to discuss diagnostic and therapeutic standards for this airway compartment. TRIAL REGISTRATION NUMBER: NCT00266474.

From registry to quality management: the German Cystic Fibrosis Quality Assessment project 1995 2006.

Since 1995, the German Cystic Fibrosis Quality Assessment project has collected demographic data and outcome parameters. It aims to develop tools for quality management. The basic data of 6,835 patients has been collected annually by 93 centres. Weight for height and body mass index (BMI) indicated nutritional status, and forced expiratory volume in one second (FEV(1)) served as the central respiratory parameter. Data on mortality and survival were calculated. The mean age of all patients has increased from 13.9 yrs in 1995 to 17.7 yrs in 2005, and the percentage of adult patients has increased from 28.4 to 43.4%. Benchmarking diagrams and centre reports indicated considerable differences between the centres. The achievement of basic aims at the age of 6, 12 and 18 yrs indicated a positive development in 1995 to 2005. In 2005, median age at death was 23.7 yrs and the median cumulative survival was 37.4 yrs. Mortality correlated with a BMI <19 kg x m(-2) and an FEV(1) <80%. No sex gap in mortality was detected. "Learning from the best" is now possible. Further improvements in the system of cystic fibrosis care are required, such as: defining alarm signals for early treatment; involvement of patients and their families in quality management; auditing; benchmarking; and in-house training.

Evaluation of body mass index percentiles for assessment of malnutrition in children with cystic fibrosis.

OBJECTIVE: To compare the performance of recently released body mass index percentiles (BMIp) with standard anthropometric indexes, including height-for-age percentile (HAP), weight-for-age percentile (WAP) and percent ideal body weight (%IBW), as measures for nutritional failure in children with cystic fibrosis (CF). DESIGN: Cross-sectional analysis of growth and lung function data from 4577 children with CF reported to the German CF quality assurance (CFQA) project from 1995 to 2004. RESULTS: Frequency distribution of HAP (mean+/-s.d.: male 30.0+/-27.5; female 31.3+/-27.4) and WAP (male 28.9+/-27.0; female 29.6+/-26.7) were skewed, with significant numbers of patients below the fifth percentiles of a healthy reference population. However, because deficits occurred in both measures simultaneously, mean %IBW (male 97.0+/-12.1; female 98.1+/-12.3) assumed subjects weight close to the nominal weight-for-height at all ages. In contrast, mean BMIp was markedly reduced (male 35.7+/-27.9; female 35.6+/-27.2) and steadily declined with age. Ideal weight-for-age was significantly lower when predicted by %IBW compared with BMIp method, particularly in subjects with shorter-than-average stature. Consequently, less CF children were identified with nutritional failure according to %IBW method (male 20.5%; female 22.7%) compared with BMIp method (male 30.4%; female 28.7%). The clinical relevance of these findings was confirmed by stronger correlation of BMIp with impaired %forced expiratory volume/s, a marker for disease progression in CF. CONCLUSION: BMIp predicts nutritional failure more sensitively and accurately than conventional anthropometric indexes, at least in children with CF. Screening of CF patients by BMIp could provide an early warning sign and allow for timely therapeutic intervention.

[Acute pain management in proximal femoral fractures: femoral nerve block (catheter technique) vs. systemic pain therapy using a clinic internal organisation model]. / Akutschmerztherapie bei Patienten mit hüftgelenknahen Frakturen : N.-femoralis-Katheter-Analgesie vs. systemische Schmerztherapie unter Anwendung eines klinikinternen Organisationsmodells.

BACKGROUND: The aim of this study was to compare safety and efficacy of catheter-mediated femoral nerve block analgesia with systemic pain therapy in patients with proximal femoral fractures in the pre-operative and post-operative setting using a protocol for coordinating pain management. METHODS: In a prospective randomised trial of patients attending the emergency department, 100 individuals were selected with a clinically diagnosed proximal femoral fracture. Patients were divided into two equal groups A and B. Group A (n=50) received a catheter-mediated femoral nerve block with 1% prilocaine (40 ml) and post-operatively 0.2% ropivacaine (30 ml) 6 hourly. Group B (n=50) initially received intravenous metamizol (1 g) and a fixed combination of oral tilidine (100 mg) + naloxone (8 mg). Patients aged 90 years or more received a reduced dose (tilidine 75 mg + naloxone 6 mg). In the post-operative period regular oral ibuprofen (400 mg, 8 hourly) in addition to oral tilidine (50 mg) + naloxone (4 mg) was given as required for break through pain. Pain intensity was measured using a verbal rating scale (VRS) from 1 to 5: pain free (=1), mild pain (=2), moderate pain (=3), severe pain (=4), excruciating pain (=5). Pain scores were recorded at rest (R), during passive anteflection (30 degrees) of the hip (PA) on arrival and at 15 and 30 min after initial administration of analgesia. Thereafter, recordings were made 4 times a day up to the third post-operative day. RESULTS: Pain scores were comparable for both groups on admission (VRS in R 2.50 vs. 2.46; VRS during PA 4.30 vs. 4.34). Significant pain relief was achieved in both groups following initial administration of analgesia, but the total pain scores in group A were significantly lower than in group B (VRS in R 1.22 vs. 1.58, p<0.01 and VRS during PA 2.66 vs. 3.26; p<0.001). No difference was noted between the two groups during the first 3 post-operative days. No severe complications occurred as a result of analgesia, however, the catheter was dislodged in 20% of patients in group A resulting in the need for systemically administered analgesia. CONCLUSION: All patients presenting with proximal femoral fractures should receive adequate analgesia within the emergency department even prior to radiographic imaging. Femoral nerve block should be considered as the method of choice. The insertion of a femoral nerve block catheter has the dual advantage of early analgesia permitting repeated clinical examination in addition to continued post-operative pain management. The cumbersome logistics inherent in this technique within the clinical setting limits its practical application. An initial single-shot regional nerve block followed by a systemic post-operative analgesia protocol was considered an appropriate alternative. The execution of safe, consistent and appropriate regional nerve block anaesthesia is reliant on formal guidelines and protocols as agreed by the multidisciplinary teams involved with patient-directed pain management and good clinical practice.

[Preoperative hypervolemic hemodilution with 6% hydroxyethyl starch 130/0,4 (HES 130/ 0.4) solution as a way of reducing needs for donor blood transfusion].

UNLABELLED: The efficacy of hypervolemic hemodilution (HHD) in reducing the rate of donor blood transfusion is controversely discussed. The present prospective, randomized, clinical study analyzes the impact of HHD with 6% hydroxyethyl starch (HES) 130/0.4 solution on the rate transfusion, laboratory parameters, and the incidence of complications as compared with those in the control group receiving no preoperative HHD. MATERIAL AND METHODS: 80 patients who had undergone total prostatectomy or cystectomy were randomized into 2 groups. Before anesthesia, the HHD group (n=40) received 15 ml/kg of 6% HES 130/0.4 solution. In the HHD and control (n=40) groups, 6% HES 130/0.4 was intraintraoperatively infused in its maximum dose of 33 ml/kg according to the patients' needs. Indicationsf or blood transfusion trigger were Hb <5 g/dl or packed cell volume < 0.24. Laboratory parameters (Hb, PCV, platelets, prothrombin index, prothrombin time, thrombin time, fibrinogen, antithrombin III were measured before surgery, after HHD and 2, 24, and 48 hours after surgery. The mean blood pressure (MBP), heart rate (HR), and central venous pressure (CVP) were determined before surgery, after HHD, and 2 hours postsurgery. Statistical measurements were made in all patients from the HHD and control groups, as well as in a subgroup, in which intraoperative blood loss was greater than 30% of the total blood volume (70 ml/kg body weight). RESULTS: Demographic data and surgical techniques were similar in both groups. After HHD, CVP rose significantly. The changes in MBP and HR were statistically insignificant. There were no complications after HHD. Of the 40 HHD-group patents, 5 needed donor blood transfusion while in the control group blood was transfused to 10 of the 40 patients in the control group. Comparing both groups showed a lower need for blood transfusion in the HHD-group patients than in the controls (10 versus 24 packed red cells). The postoperative Hb values showed no difference between both groups. CONCLUSIONS: Preoperative HHD in patients undergoing surgery with expected >30% blood loss leads to decreased needs for blood transfusion. The method is safe and easy-to-use.

Prospective evaluation of emerging bacteria in cystic fibrosis.

BACKGROUND: Bacteria contribute considerably to the progression of lung disease in cystic fibrosis. In this prospective, multi-centre study, we aimed to evaluate the occurrence of emerging bacteria and the physicians' assessments of the clinical importance of these findings. METHODS: Twelve CF centres (total number of patients: 1419) reported the detection of any Stenotrophomonas maltophilia, Burkholderia cepacia complex, MRSA, Alcaligenes xylosoxidans, Klebsiella species and Mycobacteria during an observation period of 6 months. RESULTS: 213 specimens with emerging bacteria were reported from 145 different patients. The proportion of patients with emerging bacteria differed between centres (3-38%, mean: 12.6%) and increased with age. The predominant bacterium was S. maltophilia (n=106 positive specimens), followed by Klebsiellae (n=36), B. cepacia complex (n=31), A. xylosoxidans (n=16), Mycobacteria (n=11), MRSA (n=11), and others (n=2). In many instances the same microorganisms had already been reported earlier, indicating intermittent or chronic colonisation. The clinical status was reported to be stable in 70% of patients, and antibiotic treatment was anticipated for 46% of positive specimens. Comparison of clinical data to age matched controls did not reveal any significant differences with regard to pulmonary and nutritional status prior to detection of emerging bacteria. CONCLUSION: These data suggest a high variability between centres regarding the prevalence of emerging bacteria. Most patients maintained a stable clinical condition during the 6-month study period despite being colonised with emerging bacteria.

Resistance development to fluoroquinolones in Europe.

We did not observe an increase in quinolone-resistant strains in recent years despite a dramatic increase in drug usage. P. aeruginosa strains should be carefully monitored in the future since a trend to increased MICs seems obvious. Epidemiologic data on resistance have to be evaluated carefully, and special interest must be focused on the breakpoint in relation to the normal distribution of MICs. Conclusions can be drawn only if the increased numbers of strains are clearly separated from the normal distribution.

Microbiological evaluation of cefpodoxime proxetil.

Cefpodoxime, the active de-esterified molecule of the orally absorbable cephalosporin cefpodoxime proxetil, inhibits streptococci, Neisseria spp., and most Enterobacteriaceae, with MIC50 and/or MIC90 values of less than or equal to 2 mg/L; with regard to the latter family of bacteria, the MIC50 and/or MIC90 values of cefpodoxime are consistently greater than or equal to 4 mg/L for only Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Morganella morganii. The MIC50 of cedpodoxime for coagulase-negative staphylococci is greater than 2 mg/L, while the MIC for Staphylococcus aureus strains is 4 mg/L. In comparison with other orally absorbable cephalosporins, cefpodoxime is slightly less active than cefixime, cefetamet, and cefotiam against Gram-negative bacteria, but more active than cefuroxime, cefaclor, and cefalexin. Against staphylococci, the activity of cefpodoxime is comparable to that of cefotiam and cefuroxime, and superior to that of cefaclor, while cefixime and cefetamet have insufficient activity against these species. In common with other cephalosporins, cefpodoxime has no activity against enterococci. In vitro models simulating human serum cefpodoxime concentrations demonstrate that a dosage regimen of 200mg is probably sufficient to treat most infections. However, further study is needed to clarify whether infections due to bacteria such as S. aureus, with higher cefpodoxime MICs, can be treated with this dose regimen.

Cefotaxime. Unchanged antibacterial activity over years?

During recent years new mechanisms of beta-lactam resistance have developed with the genetic origin on the chromosome or plasmids. Nevertheless, most multicenter studies can demonstrate that cefotaxime has retained its antibacterial activity toward the relevant species. However, it is important to follow the development of resistance closely in hospitals, where epidemic outbreaks of bacterial strains with extended-spectrum beta-lactamases can create difficulties in the treatment of infectious diseases.

Induction of beta-lactamase in Gram-negative bacteria.

The induction of beta-lactamase in Gram-negative bacteria in vitro has been established. It is possible to distinguish between high and low beta-lactamase inducers in vitro. This differentiation is clinically irrelevant because induction has little effect on the treatment of a bacterial infection with beta-lactam antibiotics. Regardless of the amount of induced beta-lactamase, the kill kinetics are usually not affected. In mutated cells, the regulatory mechanism is destroyed by inactivation of the relevant genes with respect to their regulatory function, particularly by inactivation of the amp D gene. These mutants overproduce the beta-lactamase constitutively, which results in an enzyme level that significantly exceeds the induced level. The induction process is probably not the cause of clinical failures associated with the use of beta-lactam antibiotics. It is concluded that the selection of resistant mutants with constitutive overproduction of beta-lactamase is the reason for most of these treatment failures.

Natural antibiotic susceptibility of Escherichia coli, Shigella, E. vulneris, and E. hermannii strains.

The natural antibiotic susceptibility of 139 Escherichia coli strains (including 18 enterohemorrhagic E. coli), 73 Shigella strains (S. sonnei (n = 37), S. flexneri (n = 29), S. boydii (n = 6), S. dysenteriae (n = 1)), 23 E. vulneris, and 20 E. hermannii strains toward 71 antibiotics was examined. MICs were determined using a microdilution procedure. All examined taxa were naturally sensitive/intermediate toward tetracyclines, aminoglycosides, some penicillins (amoxycillin/clavulanate, ampicillin/sulbactam, piperacillin [with and without tazobactam], mezlocillin, azlocillin), cephalosporins, carbapenems, monobactams, quinolones, trimethoprim, cotrimoxazole, and chloramphenicol and were naturally resistant/intermediate toward benzylpenicillin, oxacillin, macrolides, lincosamides, glycopeptides, rifampicin, and fusidic acid. No differences in natural antibiotic susceptibility were seen between enterohemorrhagic and other E. coli strains. Likewise, with one exception, no significant differences in natural antibiotic susceptibility were seen either among the Shigella subgroups or between Shigella and E. coli. The natural population of S. flexneri was slightly more susceptible to chloramphenicol than the natural populations of other taxa within the Shigella-E. coli complex. E. vulneris and E. hermannii showed susceptibility patterns to many antibiotics similar to Shigella and E. coli, but there were other antibiotics toward which there were significant differences in natural susceptibility. E. vulneris and E. hermannii were less susceptible to nitrofurantoin and slightly more susceptible to several aminoglycosides than E. coli and Shigella. E. hermannii was the only species that was naturally resistant/intermediate to ticarcillin and amoxycillin (DIN standard). The addition of clavulanic acid to the latter resulted in a decrease of seven twofold dilution steps (E. vulneris: four twofold dilution steps, E. coli/Shigella: two twofold dilution steps) of the MICs of the natural population. With the exception of cefoperazone and cefepime, E. hermannii was more susceptible to cephalosporins than strains of the other species. E. vulneris was the species most susceptible to ticarcillin and the only species that was highly resistant to fosfomycin (MIC > 256 micrograms/mL). The antibiotic susceptibility to fosfomycin was also unique for E. hermannii (MIC 32-128 micrograms/mL), whereas the natural populations of E. coli and Shigella showed lower MIC values. The data of this study represent an assessment of the natural susceptibility of strains of Escherichia spp. and Shigella subgroups to a wide range of antibiotics. These databases can be used for the validation of antibiotic susceptibility test results of Escherichia spp. and shigellae. The conformity of the natural antibiotic susceptibility test results not only among the Shigella subgroups but also between Shigella and E. coli support the status of Shigella as a subgroup of the species E. coli.

Identification and natural antibiotic susceptibility of Morganella morganii.

Our data should elucidate whether or not natural antibiotic susceptibility can be used as an aid for subspecies or biovar discrimination of Morganella morganii (II). Furthermore, our goal was to create a database of the natural susceptibility of M. morganii (III) and we were interested in the relative frequency of the recently described subspecific taxa (I). On the basis of trehalose fermentation (TRE), ornithine decarboxylase (ODC), and lysine decarboxylase (LDC) activities, we determined the biovar for 90 clinical isolates of M. morganii. Within these strains we examined the natural antibiotic susceptibility of 53 morganellae to 70 antibiotics by determination of the MICs with a microdilution procedure. (I): 80 strains (89%) of all morganellae belonged to M. morganii ssp. morganii (TRE-), with biovar A (LDC-, ODC+) predominating (67 strains). The remaining strains of this subspecies were identified as biovar B (LDC+, ODC+; 12 strains) and biovar C (LDC-, ODC-, one strain). Ten strains of M. morganii ssp. sibonii (TRE+) were found: four strains belonged to biovar F (LDC variable, ODC-) and six strains to biovar G (LDC-, ODC). (II): With one exception we found no significant differences in antibiotic susceptibility between different biovars. M. morganii ssp. morganii strains are more susceptible to tetracycline than strains of M. morganii ssp. sibonii, but there is no evidence that this parameter could be useful to differentiate biovars within a subspecies. It could be shown that 8 of 30 strains of biovar A and 2 of 12 strains of biovar B were tetracycline resistant. However, one M. morganii ssp. sibonii strain was clinically susceptible to tetracycline according to French and American standards. (III): The natural population of M. morganii is primarily (naturally) resistant to certain penicillins like benzylpenicillin, oxacillin, and amoxicillin, first and second generation cephalosporins (excluding cefoxitin), cefpodoxime, all antibiotics of the ML group (macrolides and lincosamides), sulfamethoxazole, glycopeptides, fosfomycin, and fusidic acid, naturally sensitive to aminoglycosides, piperacillin, mezlocillin, ticarcillin, third and fourth generation cephalosporins, carbapenems, aztreonam, quinolones, trimethoprim, cotrimoxazole, and chloramphenicol. M. morganii is naturally resistant to a wide range of antibiotics. The natural resistance pattern is useful for validation of sensitivity tests. Susceptibility to antibiotics is an unsuitable parameter for the discrimination of the described subspecific taxa of M. morganii. M. morganii strains that do not belong to biovar A are rare.

The negative regulator of beta-lactamase induction AmpD is a N-acetyl-anhydromuramyl-L-alanine amidase.

Construction of a malE-ampD gene fusion allowed purification of biologically active fusion protein by affinity chromatography. The cloned malE-ampD gene fusion complemented a chromosomal ampD mutation. Purified MalE-AmpD fusion protein was found to have murein amidase activity with a pronounced specificity for 1,6-anhydromuropeptides, the characteristic murein turnover products in Escherichia coli. Being a N-acetyl-anhydromuranmyl-L-alanine amidase AmpD is likely to be involved in recycling of the turnover products. It is suggested that the negative regulatory effect of AmpD is due to the hydrolysis of anhydro-muropeptides which may function as signals for beta-lactamase induction.

Natural antibiotic susceptibility of Providencia stuartii, P. rettgeri, P. alcalifaciens and P. rustigianii strains.

The natural antibiotic susceptibility of 38 Providencia rettgeri, 35 P. stuartii, 23 P. alcalifaciens and 20 P. rustigianii strains was examined. MIC values were determined by a microdilution procedure and evaluated by a table calculation programme. P. stuartii was the least susceptible Providencia sp. and was naturally resistant to tetracyclines, some penicillins, older cephalosporins, sulphamethoxazole and fosfomycin and to antibiotics to which other species of Enterobacteriaceae are also resistant. It was naturally sensitive to modern penicillins and cephalosporins, carbapenems and aztreonam, but its susceptibility to aminoglycosides and quinolones was difficult to assess. P. alcalifaciens and P. rustigianii strains were the most susceptible Providencia spp. They were naturally sensitive or intermediate to tetracyclines and sensitive to aminoglycosides and quinolones. Susceptibility to sparfloxacin, biapenem and sulphamethoxazole permitted the discrimination of P. alcalifaciens and P. rustigianii strains. The natural antibiotic susceptibility of P. rettgeri strains was between that of P. stuartii and that of the other providenciae. P. rettgeri was resistant to tetracyclines and fosfomycin, but more susceptible to aminoglycosides, quinolones, fosfomycin and numerous beta-lactam antibiotics than P. stuartii. A database is described of the natural antibiotic susceptibilities of Providencia spp. It can be used for the validation of antibiotic susceptibility test results of these micro-organisms.

Natural antibiotic susceptibility of Enterobacter amnigenus, Enterobacter cancerogenus, Enterobacter gergoviae and Enterobacter sakazakii strains.

OBJECTIVE: To investigate the natural susceptibility to 69 antimicrobial agents of 107 Enterobacter strains comprising E. amnigenus (n = 18), E. cancerogenus (n = 26), E. gergoviae (n = 28) and E. sakazakii (n = 35). METHODS: Minimal inhibitory concentrations (MICs) were determined with a microdilution procedure in Isosensitest broth and cation-adjusted Mueller-Hinton broth. RESULTS: All the species were naturally sensitive or intermediate to tetracyclines, amino-glycosides, numerous beta-lactams (acylureidopenicillins, ticarcillin, ampicillin/sulbactam, several cephalosporins, carbapenems, aztreonam), quinolones, antifolates, chloramphenicol and nitrofurantoin. Natural resistance was found to penicillin G, oxacillin, several macrolides, lincosamides, streptogramins, glycopeptides, rifampicin and fusidic acid. Species-related differences in natural susceptibility were found to some beta-lactams, azithromycin and fosfomycin. Whereas E. gergoviae was the most susceptible species to azithromycin, E. cancerogenus was most susceptible to fosfomycin and was the only species showing natural resistance to amoxicillin, amoxicillin/clavulanic acid, cefaclor, cefazoline, loracarbef and cefoxitin. There were only minor medium-dependent differences in susceptibility to most antibiotics. CONCLUSIONS: The present study establishes a database concerning the natural susceptibility of recently established Enterobacter species to a wide range of antibiotics, which can be applied for the validation of routine susceptibility test results. beta-Lactam susceptibility patterns indicate the expression of species-specific beta-lactamases expressed at high or low levels in all the species except E. sakazakii.

Natural antimicrobial susceptibility patterns and biochemical profiles of Leclercia adecarboxylata strains.

Leclercia adecarboxylata is an opportunistic human pathogen that phenotypically resembles Escherichia coli. The natural susceptibilities of 101 Leclercia strains to 70 antimicrobial agents were investigated. MICs were determined with a microdilution procedure in cation-adjusted Mueller-Hinton broth (all strains) and IsoSensitest broth (some strains). Natural susceptibility patterns were assessed using German (DIN) standards (when applicable). In addition, biochemical properties recommended for the phenotypic identification of L. adecarboxylata were evaluated, applying two commercially available identification systems for Enterobacteriaceae and seven conventional tests. L. adecarboxylata strains were naturally sensitive to tetracyclines, aminoglycosides, all but two beta-lactams, quinolones, folate pathway inhibitors, chloramphenicol, nitrofurantoin and azithromycin. They were naturally resistant to penicillin G, oxacillin, erythromycin, roxithromycin, clarithromycin, ketolides, lincosamides, streptogramins, linezolid, glycopeptides, rifampicin, fusidic acid and fosfomycin. There were only minor medium-dependent differences in susceptibility to most antibiotics. Lysine decarboxylase, malonate assimilation and acid production from arabitol and cellobiose, but not from adonitol and sorbitol, allowed definitive separation of L. adecarboxylata from E. coli. The results of this study form a database that can be applied to validate forthcoming antibiotic susceptibility tests of L. adecarboxylata, and might contribute to its reliable identification. Susceptibility patterns did not indicate obvious therapeutic difficulties for treatment of Leclercia infections. Special attention should be paid to biochemically aberrant leclerciae. Apart from biochemical features, fosfomycin susceptibility might be useful to differentiate between L. adecarboxylata and E. coli.

Natural antibiotic susceptibility of Listeria species: L. grayi, L. innocua, L. ivanovii, L. monocytogenes, L. seeligeri and L. welshimeri strains.

OBJECTIVE: To investigate the natural susceptibility to 71 antimicrobial agents of 103 Listeria strains belonging to all known Listeria species (L. monocytogenes (N = 21), L. innocua (N = 21), L. seeligeri (N = 21), L. ivanovii (N = 19), L. welshimeri (N = 11), and L. grayi (N = 10)). METHODS: MICs were determined using a microdilution procedure in H-Medium. RESULTS: All listeriae were naturally sensitive or intermediate to tetracyclines, aminoglycosides, penicillins (except oxacillin), loracarbef, cefazoline, cefaclor, cefotiam, cefoperazone, carbapenems, macrolides, lincosamides, glycopeptides, dalfopristin/quinupristin, chloramphenicol and rifampicin (probably except L. grayi). Listeria spp. were naturally resistant or intermediate to most 'modern' cephalosporins (cefetamet, cefixime, ceftibuten, ceftazidime, cefdinir, cefpodoxime, cefotaxime, ceftriaxone, cefuroxime), aztreonam, pipemidic acid, dalfopristin quinupristin and sulfamethoxazole. Significant differences in natural susceptibility among the species were seen with the quinolones, trimethoprim, co-trimoxazole, rifampicin, fosfomycin and fusidic acid. It seems likely that L. grayi is naturally resistant to all antifolates; the species was least susceptible to rifampicin and most susceptible to quinolones, whereas L. ivanovii was naturally resistant to most quinolones. L. ivanovii was naturally sensitive to fosfomycin, whereas L. innocua and L. monocytogenes were naturally resistant. L. ivanovii was also the most susceptible species to fusidic acid. CONCLUSIONS: The present study describes a database on the natural susceptibility of Listeria spp. to a wide range of antibiotics, which can be used to validate susceptibility testing results of these microorganisms.

Natural antibiotic susceptibility of Salmonella enterica strains.

The susceptibility of 100 Salmonella enterica strains belonging to S. enterica subsp. enterica (n=90) and S. enterica subsp. arizonae (n=10) was examined to 71 antibiotics. Within S. enterica subsp. enterica, strains of different serovars (typhimurium (n=17), enteritidis (n=17), dublin (n=10), typhi (n=16), paratyphi A (n=6), others (n=24)) were studied. MICs were determined using a microdilution procedure and apart from fosfomycin there were no significant differences in susceptibility between the subspecies and serovars of S. enterica. All salmonellae were sensitive or intermediately resistant to tetracyclines, aminoglycosides, most beta-lactam antibiotics, quinolones, co-trimoxazole group antibiotics, chloramphenicol, nitrofurantoin and azithromycin. S. enterica strains were intrinsically resistant to benzylpenicillin, oxacillin, most macrolides, rifampicin, lincosamides, streptogramins, glycopeptides and fusidic acid. Apart from some slight differences in antibiotic susceptibility between strains of S. enterica subsp. enterica and S. enterica subsp. arizonae, only the susceptibility to fosfomycin varied among the taxa studied. Whereas 'enteric' salmonellae including S. enterica subsp. arizonae were sensitive to fosfomycin, 'typhoid' salmonellae were intrinsically resistant. A database of the antibiotic susceptibility of S. enterica was set up. It may be of use to validate antibiotic susceptibility test results of these bacteria.

Natural antibiotic susceptibility of strains of Serratia marcescens and the S. liquefaciens complex: S. liquefaciens sensu stricto, S. proteamaculans and S. grimesii.

The natural susceptibility of 77 strains of Serratia marcescens and 41 strains of the S. liquefaciens complex (S. liquefaciens sensu stricto (n=21), S. grimesii (n=10), S. proteamaculans (n=10)) to 70 antibiotics was examined using a microdilution procedure in Isosensitest broth (all strains) and cation-adjusted Mueller Hinton broth (some strains). All species were naturally resistant to benzylpenicillin, oxacillin, cefaclor, cefazolin, cefuroxime, numerous macrolides, lincosamides, streptogramins, glycopeptides, rifampicin and fusidic acid. Uniform natural sensitivity was found to most aminoglycosides, several acylureidopenicillins, ticarcillin, newer cephalosporins, carbapenems, aztreonam, quinolones and antifolates. Species-related differences in susceptibility affecting clinical assessment criteria were found for several agents. S. marcescens was less susceptible to some aminoglycosides than species of the S. liquefaciens group. It was the only species that was uniformly naturally resistant to tetracycline, amoxycillin, amoxycillin/clavulanate and loracarbef. Species of the S. liquefaciens group were naturally resistant and intermediate or naturally intermediate to the latter agents. Differences in susceptibility among the species of the S. liquefaciens complex were generally small. S. proteamaculans was most susceptible to sulphamethoxazole. S. liquefaciens sensu stricto was less susceptible than S. grimesii and S. proteamaculans to tetracyclines, chloramphenicol and nitrofurantoin; it was the only species uniformly naturally resistant to fosfomycin. This study suggested that all species examined probably express chromosomally-encoded AmpC beta-lactamases, but the amount of enzyme may vary from species to species. The naturally-occurring low-level expression of the S. marcescens aminoglycoside 6'-acetyltransferase AAC(6')-Ic and its absence in other Serratia spp. was supported by the data. All species of the S. liquefaciens complex should be considered as probable agents of human diseases.