Surveillance of antibiotic resistance in non invasive clinical isolates of Streptococcus pneumoniae collected in Belgium during winters 2003 and 2004.

A total of 391 and 424 non-invasive isolates of Streptococcus pneumoniae collected by 15 laboratories during the 2003 and 2004 survey were tested for their susceptibility by a microdilution technique following NCCLS recommendations. Insusceptibility rates (IR) in the two surveys (2003/2004) were as follows: penicillin 15.0/14.7% [8.4/6.4% Resistance (R)], ampicillin 17.4/14.6% (R 9.0/7.1%), amoxicillin +/- clavulanic acid 2.6/1.2 % (R 0/0%), cefaclor 14.3/14.1% (R 11.5/13.4%), cefuroxime 13.6/12.7% (R 10.5/11.8%), cefuroxime-axetil 10.5/11.8% (R 10.0/9.2%) (breakpoints based on 250 mg), cefotaxime 4.9/6.2% (R 1.3/2.4%), ceftazidime NotTested (NT)/6.4 (R NT/2.6%), cefepime NT/6.4 (R NT/2.6%), imipenem 7.7/8.9 % (R 1.8/1.4%), ertapenem 0.8/NT% (R O/NT%), ciprofloxacin 13.8/9.0% (R 4.3/2.4%), levofloxacin 3.3/2.8% (R 1.5/0.2%), moxifloxacin 0.6/0.2% (R 0.3/0%), ofloxacin 13.5/9.0% (R 4.3/2.4%), erythromycin 26.1/24.7% (R 25.3/24.5%), azithromycin 25.4/24.7% (R 24.6/24.5%), telithromycin 0.8/0.2% (R 0.5/0%), clindamycin 21.2/18.4% (R 19.2/17.7%) and tetracycline 32.3/22.1% (R 29.2/19.3%). There were only minor differences in resistance rates according to age, sample site, admission type (i.e. ambulatory, hospitalized or long-term care facility patients), gender and geographic origin. Overall, telithromycin (MIC50, MIC90 in 2003/2004: 0.015 microg/ml, 0.12 microg/ml/ 0.008,0.06 respectively), ertapenem (0.03; 0.25/NT), moxifloxacin (0.06; 0.25/0.06, 0.12), and amoxicillin +/- clavulanic acid (0.03; 0.25/0.015, 0.5) were the most active compounds in both surveys. In 2003, the most common resistance phenotype was isolated insusceptibility to tetracycline (10.5%) followed by combined insusceptibility to erythromycin and tetracycline (9.3%). Erythromycin-tetracycline resistance (10.4%) was the most common in 2004. Isolates showing resistance to an antibiotic were significantly more present in 2003 than in 2004 (50.4% versus 40.8%). In penicillin-insusceptible isolates, MICs of all beta-lactams were increased but cross-resistance between penicillin and other beta-lactams in the penicillin-insusceptible isolates was not complete. In the 2003 survey, most of these isolates remained fully susceptible to ertapenem (94.9%) and amoxicillin +/- clavulanic acid (83.1%). In the 2004 survey, 91.9% of the penicillin insusceptible isolates remained susceptible to amoxicillin +/- clavulanic acid. In both surveys, the most common serotypes in penicillin insusceptible isolates were 14, 23,19 and 9 (20.0%, 20.0%, 16.4% and 10.9% respectively in 2003; 41.6%, 11.7%, 15.0% and 18.3% respectively in 2004).

Surveillance of antibiotic resistance in clinical isolates of Streptococcus pneumoniae collected in Belgium during winter 2000-2001.

A total of 314 isolates of Streptococcus pneumoniae collected by 10 different laboratories were tested for their susceptibility by using a microdilution technique following NCCLS recommendations. The following antibiotics were included: penicillin, ampicillin, amoxicillin, amoxicillin/clavulanate, cefaclor, cefuroxime, cefotaxime, imipenem, ciprofloxacin, gemifloxacin, levofloxacin, erythromycin, clarithromycin, azithromycin, miocamycin, clindamycin and tetracycline. The insusceptibility rate (IR) to penicillin was 21.0% [10.8% intermediate (> or = 0.12-1 microgram/mL) and 10.2% high-level (> or = 2 micrograms/mL)], to cefotaxime 7.3% [3.5% intermediate (> or = 1 microgram/mL) and 3.8% high-level (> or = 2 micrograms/mL)], to imipenem 3.8% [3.8% intermediate (> or = 0.25-0.5 microgram/mL) and 0% high-level (> or = 1 microgram/mL)], to ciprofloxacin 11.2% [8.3% intermediate (2 micrograms/mL) and 3.9% high-level (> or = 4 micrograms/mL)], to erythromycin 30.3% [3.5% intermediate (0.5 microgram/mL) and 26.8% high-level (> or = 1 microgram/mL)] and to tetracycline 38.5% [0.9% intermediate (4 micrograms/mL) and 37.6% high-level (> or = 8 micrograms/mL)]. No decreased susceptibility was found for gemifloxacin (> or = 0.5 microgram/mL). This compound was the most active with MIC50, MIC90 and an IR of 0.015 microgram/mL, 0.03 microgram/mL and 0% respectively, followed by amoxicillin/clavulanate, amoxicillin and imipenem (MIC50, MIC90 and IR: 0.015 microgram/mL, 1 microgram/mL, 1.6%/0.015 microgram/mL, 1 microgram/mL, 1.9%/0.008 microgram/mL, 0.12 microgram/mL, 3.8% respectively). Compared to the 1999 surveillance, penicillin and tetracycline-insusceptibility increased with 4.9% and 15.6% respectively, while cefotaxime, erythromycin and ciprofloxacin insusceptibility decreased with 5.4%, 5.8% and 4.4% respectively. MICs of all beta-lactams rose with those of penicillin for penicillin-insusceptible isolates. Imipenem, cefotaxime, amoxicillin and amoxicillin/clavulanate were generally 4, 2, 1 and 1 doubling dilutions respectively more potent than penicillin on these isolates while ampicillin, cefuroxime and cefactor were generally 1, 2 and 4 dilutions respectively [table: see text] less potent. Most penicillin-insusceptible isolates remained fully susceptible to amoxicillin/clavulanate (92.4%), amoxicillin (90.9%) and imipenem (81.8%). Erythromycin-tetracycline insusceptibility was the most common resistance phenotype (14.3%). Three- and four-fold resistance was found in 12.4% and 1.6% respectively of the isolates. Most penicillin-insusceptible isolates were of capsular types 14 (22.7%), 23 (21.2%), 6 (18.2%), 9 (13.6%) and 19 (12.1%).

Study of the in vitro activity of amoxicillin/clavulanic acid and other beta-lactam antibiotics against Escherichia coli isolated from urine specimens.

A total of 205 serial, unduplicated urinary isolates of Escherichia coli was collected from June through August 1998 in 2 community and 3 hospital laboratories. By using the NCCLS broth microdilution technique, their in vitro susceptibility to ampicillin, amoxicillin/clavulanic acid, cefuroxime, cefuroxime axetil, ticarcillin/clavulanic acid and piperacillin/tazobactam was determined. One hundred and twenty isolates were from hospitalised patients, 85 from ambulatory, 129 community acquired and 76 nosocomial. Half of the nosocomial isolates were obtained from naturally produced and half from alternatively produced urine specimens. In general, the highest susceptibility rates, following NCCLS criteria, were found for piperacillin/tazobactam (93.2%) followed by cefuroxime (92.2%) and amoxicillin/clavulanic acid (82.9%). Ampicillin showed a clear bimodal distribution with a clear peak for the resistant population. The highest degree of ampicillin resistance was found in nosocomial isolates. Overall, ampicillin showed the lowest degree of susceptibility. Most of the ampicillin resistant isolates remained susceptible to piperacillin/tazobactam, cefuroxime and amoxicillin/clavulanic acid. In general, the community acquired isolates had higher susceptibility rates than the nosocomial isolates.

Comparative in vitro activity of temocillin and other antimicrobial agents against Enterobacteriaceae isolated from patients admitted to five Belgian hospitals.

Temocillin, a methoxy-derivative of the broad-spectrum penicillin, ticarcillin, has been introduced into clinical practice in Belgium in 1988. Since then, not many surveys of its in vitro activity have been published. This study addresses this issue in a prospective collection of 300 consecutive Gram-negative isolates originating from in-patients in five general hospitals throughout Belgium. In addition to temocillin, seven common antibiotics were tested: amoxicillin-clavulanate, piperacillin-tazobactam, cefotaxime, aztreonam, meropenem, ciprofloxacin and amikacin. Meropenem appeared to exhibit the best activity overall, whereas amoxicillin-clavulanate scored the worst. Cumulative MIC plot for two subsets of organisms are given: temocillin, meropenem and cefotaxime are the most active on E. coli and Klebsiella spp., while a significant percentage is resistant to ciprofloxacin and amoxicillin-clavulanate. In the group of inducible Enterobacteriaceae, temocillin, meropenem and amikacin are the most active drugs, while the activity of amoxicillin-clavulanate, piperacillin-tazobactam, cefotaxime and ciprofloxacin is largely decreased. Taking this well preserved in vitro activity of temocillin into account, and looking at its convenient pharmacokinetics and low cost of acquisition, this drug may prove a useful alternative in the treatment of severe nosocomial infections.

In vitro study on the antimicrobial activity of various antibiotics against clinical isolates of Streptococcus pneumoniae from Belgium collected during winter 1998-1999.

A total of 205 isolates of Streptococcus pneumoniae obtained from 10 different centres were included in this study. The susceptibilities to penicillin, ampicillin, amoxicillin, amoxicillin/clavulanic acid, cefaclor, cefuroxime, cefotaxime, imipenem, ciprofloxacin, gemifloxacin, grepafloxacin, levofloxacin, trovafloxacin, erythromycin, clarithromycin, miocamycin, clindamycin and tetracycline were determined by a microdilution technique following NCCLS recommendations. Decreased susceptibility to penicillin was 16.1% [6.8% intermediate (0.12-1 microgram/mL) and 9.3% high-level (> or = 2 micrograms/mL)], cefotaxime insusceptibility (> or = 1 microgram/mL) 12.7%, ciprofloxacine insusceptibility (> or = 2 micrograms/mL) 15.6% with 1.5% of high level resistance (> or = 4 micrograms/mL), erythromycin insusceptibility (> or = 0.5 microgram/mL) 36.1% and tetracycline insusceptibility (> or = 4 micrograms/mL) 22.9%. Decreased susceptibility to cefotaxime was found in 78.8% of the penicillin-insusceptible isolates. No decreased susceptibility was found for gemifloxacin (> or = 0.5 microgram/mL) and trovafloxacin (> or = 1 microgram/mL). Compared to the 1996-1997 surveillance, penicillin, cefotaxime and erythromycin insusceptibility rose by 3.8%, 5.2% and 5.0% respectively, while tetracycline insusceptibility decreased with 8.2%. MICs of all beta-lactams rose with those of penicillin for penicillin-insusceptible isolates. Amoxicillin +/- clavulanate, cefotaxime and imipenem were generally 1, 1 and 5 doubling dilutions respectively more potent than penicillin on these isolates. Penicillin, ampicillin and cefuroxime were equally active while cefaclor was generally 5 dilutions less potent. Most penicillin-insusceptible isolates remained fully susceptible to amoxicillin +/- clavulanate and imipenem. The penicillin-insusceptible isolates were 36.4%, 27.3% and 3.0% co-insusceptible to erythromycin, erythromycin plus tetracycline and tetracycline respectively. A subpopulation of 52 isolates obtained from children aged < or = 3 years was also studied. Compared to the other isolates we found a statistically significant increase in insusceptibility for penicillin, cefaclor, cefuroxime, erythromycin, clarithromycin and tetracycline while a significant decrease was found for ciprofloxacin.

Surveillance of pneumococcal resistance in Belgium during winter 1996-1997.

This study tested 212 pneumococcal isolates from 9 institutions for their susceptibilities to penicillin, ampicillin, amoxycillin, amoxycillin/clavulanate, cefaclor, cefuroxime, cefotaxime, imipenem, tetracycline, erythromycin, and clarithromycin using NCCLS-standardized microdilution. Penicillin-insusceptibility was 12.3% [5.7% intermediate (0.12-1 microgram/ml) and 6.6% high-level (> or = 2 micrograms/ml)], tetracycline-insusceptibility (> or = 4 micrograms/ml) 31.1%, and erythromycin-insusceptibility (> or = 0.5 microgram/ml) 31.1% as well. Erythromycin-insusceptible isolates showed cross-insusceptibility to clarithromycin. Penicillin-susceptible isolates were susceptible to all beta-lactams. MICs of all beta-lactams rose with those of penicillin for penicillin-insusceptible isolates. Ampicillin and penicillin were equally potent against penicillin-insusceptible isolates, imipenem, cefotaxime, and amoxycillin +/- clavulanate were more potent (generally 5, 1, and 1 doubling dilution, respectively), and cefuroxime and cefaclor less potent (generally 1 and 6 doubling dilutions, respectively). Most penicillin-insusceptible isolates were high-level resistant to cefaclor (> or = 32 micrograms/ml). Although MICs of all beta-lactams rose with those of penicillin, resistance to penicillin was not absolute in terms of cross-resistance. Most penicillin-intermediate and high-level penicillin-resistant isolates remained fully susceptible and intermediate, respectively, to amoxycillin +/- clavulanate, cefotaxime, and imipenem, but not to cefuroxime. Penicillin-susceptible isolates were 76.9%, 42.3%, and 34.6% co-insusceptible to tetracycline, erythromycin, and tetracycline plus erythromycin, respectively. Most penicillin-, tetracycline-, and erythromycin-insusceptible isolates were of capsular types 23 >> 6 > 19 > 32, 19 > 6 > 28 > 23, and 19 > 6 > 14 > 23, respectively. Compared to winter 1994-1995, insusceptibility to penicillin, tetracycline, and erythromycin rose by some 4%, 4%, and 13%, respectively.

In vitro susceptibilities of 176 clinical isolates of Streptococcus pneumoniae to 11 beta-lactams, erythromycin, and tetracycline.

One hundred seventy six consecutive, non-duplicate pneumococcal isolates from clinical specimens collected from November 1994 through February 1995 in nine general hospitals throughout Belgium were tested for their in vitro susceptibilities to penicillin, ampicillin, amoxycillin with and without clavulanate, cefaclor, cefuroxime, cefonicid, cefprozil, cefpodoxime, cefotaxime, imipenem, tetracycline, and erythromycin by means of the NCCLS microdilution test. The overall rate of decreased susceptibility to penicillin was 12.5%, including 6.3% of intermediately and 6.3% of fully resistant isolates. Penicillin, ampicillin amoxycillin, amoxycillin/clavulanate, cefuroxime, cefotaxime and imipenem had the highest activity on a weight basis (MIC50 < or = 0.008 microgram/ml), followed by cefpodoxime and erythromycin (MIC50 of 0.015 microgram/ml), cefprozil and tetracycline (MIC50 of 0.12 microgram/ml), and eventually, cefaclor and cefonicid (MIC50 of 0.5 microgram/ml). Aggregate rates of susceptible plus intermediately resistant isolates at NCCLS-recommended breakpoints, i.e. overall percentages of isolates likely to respond to increased antibiotic doses in vivo (except for meningitis), were 100.0% for imipenem and cefotaxime, 98.9% for amoxycillin with and without clavulanate, 93.8% for penicillin, and 90.9% for cefuroxime. Overall rates of susceptibility to erythromycin and tetracycline amounted to 78.4% and 72.7%, respectively. MIC values of all beta-lactams increased with those of penicillin. Ampicillin was equally active as penicillin against isolates with reduced susceptibility to the latter (MIC90 of 2 micrograms/ml); imipenem, cefotaxime, and amoxycillin with and without clavulanate however, were more active (MIC90 3, 1, and 1 doubling dilution, respectively, below that of penicillin), while cefpodoxime, cefuroxime, cefprozil, cefonicid, and cefaclor on the other hand, were less active (MIC90, 1, 1, 2, 5, and 5 doubling dilutions, respectively, above that of penicillin). In conclusion, the present data confirm that pneumococcal resistance to penicillin has increased in Belgium, suggest that resistance to erythromycin may have stabilised, and reveal an unexpectedly high rate of resistance to tetracycline. Imipenem was the most active antibiotic tested overall, and amoxycillin with or without clavulanate the most active oral antibiotic, with activity almost similar to that of cefotaxime.

In vitro susceptibilities of 180 clinical isolates of Haemophilus influenzae to ampicillin, amoxycillin/clavulanate, cefaclor, cefuroxime, cefotaxime, clarithromycin, and azithromycin.

One hundred eighty consecutive, unduplicate isolates of Haemophilus influenzae from clinical specimens collected from November 1994 through February 1995 in nine general hospitals throughout Belgium were examined for beta-lactamase production using a nitrocefin-based test, and for their in vitro susceptibilities to ampicillin, amoxycillin/clavulanate, cefaclor, cefuroxime, cefotaxime, clarithromycin and azithromycin by means of the NCCLS agar dilution test. The isolates were all from respiratory tract specimens. The prevalence of capsular type b was 1.1%, and the overall rate of beta-lactamase production 16.7%. Rates of beta-lactamase production were higher in isolates from children (22.0%) than in those from adults (15.3%), and in isolates from upper respiratory tract specimens (22.0%) than in those from the lower respiratory tract (15.1%). Beta-lactamase-negative ampicillin resistance amounted to 1.1%. Cefotaxime had the highest activity on a weight basis [MIC (minimal inhibitory concentration) for 50% of the isolates tested (MIC50) < or = 0.06 microgram/ml], followed by ampicillin (MIC50 of 0.25 microgram/ml), amoxycillin/clavulanate and cefuroxime (MIC50 of 0.5 microgram/ml), azithromycin (MIC50 of 2 micrograms/ml), cefaclor (MIC50 of 4 micrograms/ml), and clarithromycin (MIC50 of 8 micrograms/ml). Cefotaxime was also the most active drug in terms of susceptibility rates of the isolates (100.0%), followed by amoxycillin/clavulanate and azithromycin (98.9%), cefuroxime (97.2%), cefaclor (89.4%), clarithromycin (82.8%), and ampicillin (82.2%). In conclusion, amoxycillin/clavulanate and cefuroxime retain an excellent activity against H. influenzae, while cefaclor lost some of its activity. The rate of susceptibility to azithromycin was markedly higher than that to clarithromycin; however, its ability to accumulate intracellularly while concentrations in serum and interstitial fluid remain low, should be considered, as it may represent a major drawback to its use in H. influenzae infections.

Amikacin in the treatment of gram-negative bronchopulmonary infections.

Six patients with acute gram-negative bronchopulmonary infection were treated with amikacin (15 mg/kg per day) administered intramuscularly in two equal doses at 12-hr intervals for 10-13 days. Two patients had underlying nonspecific pulmonary disease, two had advanced bronchocarcinoma, and two had extensive bronchiectasis (due to chronic aspergillosis in one patient). The pathogens were Pseudomonas aeruginosa in three patients, and Haemophilus influenzae, Klebsiella ozaenae, and Enterobacter cloacae each in one patient. Five patients recovered completely, with resolution of fever and other acute symptoms and elimination of the causative organism from sputum cultures. A moribund patient with advanced metastatic bronchocarcinoma died two days after the treatment with amikacin had been completed; the last specimen of sputum was still positive for P. aeruginosa. Tests of liver and renal function and blood counts revealed no abnormaltities. Complete audiometric survey showed no hearing loss. Nystagmography revealed reversible, lessened caloric response in some patients. Amikacin was well absorbed from the site of intramuscular injection. Levels of amikacin in serum varied among the subjects and, in some cases, for individual patients on different days.

Indirect immunofluorescence in toxoplasmosis: frequency, nature and specificity of polar staining.

In the indirect immunofluorescence test ant the Remington test for Toxoplasmosis of some sera, a polar fluorescence of the parasite has been observed. This "Polar Factor" is not observed in umbilical cord blood and in sera of children less than 6 months old, but has a relative high frequency in sera of adults. The detection of the factor depends on the nature of the used antigen. With sucrose gradient centrifugation, anti-IgM immunofluorescence, 2-mercaptoethanol-treatment and selective adsorption of sera, we could demonstrate that this factor is a non-specific IgM.

Chronic liver disease and hepatitis-B antigen: a prospective study.

A long-term follow-up of 45 patients with chronic hepatitis and 41 with cirrhosis is reported. Hepatitis-B antigen (HBAg) was present in 19 (42%) of the chronic hepatitis patients and in 20 (49%) of those with cirrhosis. The clinical course and biochemical and histological findings in the HBAg-positive and the HBAg-negative cases were similar, suggesting that HBAg-positive chronic liver disease is not a distinct clinical entity. The presence of antigen and autoantibodies was not found to be mutually exclusive. In HBAg-positive cases antigen tended to persist for months and years. When no irreversible lesions exist disappearance of the antigen may be a sign that the liver disease will resolve.