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Epidemic Pseudomonas aeruginosa serotype O16 bacteremia in hematology-oncology patients.

From 1 August 1978 through 31 December 1982, 98 hematology-oncology patients had positive cultures for Pseudomonas aeruginosa serotype O16; 22 of these patients developed bacteremia, and this bacteremia was associated with the occurrence of extensive perineal cellulitis in 10 patients (45.5%). Seventeen bacteremic patients died. The epidemic strain differed from other P. aeruginosa organisms isolated at the hospital by its resistance to all antibiotics available at that time (ticarcillin, piperacillin, azlocillin, tobramycin, ceftizoxime, ceftriaxone, moxalactam, ceftazidime, and fosfomycin). Univariate analysis showed the following factors to be significantly associated with P. aeruginosa O16 bacteremia: the severity of granulocytopenia at the time of the bacteremia, more days with fever, the administration of ticarcillin or an aminoglycoside, the receipt of a greater number of antimicrobial agents for a longer period of time before documentation of the bacteremia, and the occurrence of cellulitis. Logistic regression analysis showed that duration of fever, duration of bacteremia, and the number of antimicrobial agents administered before documentation of the bacteremia were the best predictors of P. aeruginosa O16 bacteremia. In a prospective study of the acquisition of P. aeruginosa by hematology-oncology patients, 1,149 specimens (throat and rectal swabs) from 270 patients and 201 specimens from their washbasin drains were collected. On only three occasions was the epidemic strain isolated from both the patient and his or her washbasin, but in each case the colonization of the patient preceded the isolation of the strain from the washbasin. The transmission of any P. aeruginosa organism from washbasin drain to patient could not be documented. Contact isolation precautions from the Centers for Disease Control were used for all hematology-oncology patients colonized or infected with P. aeruginosa after 7 January 1983. No case of P. aeruginosa O16 bacteremia has occurred at Hotel Dieu since July 1984.

Adult↗

Phenotypical and genotypical characterization of epidemic clumping factor-negative, oxacillin-resistant Staphylococcus aureus.

A total of 50 oxacillin-resistant Staphylococcus aureus (ORSA) strains that were clumping factor negative (CFN) and protein A negative by latex agglutination were collected from patients in six different hospitals at different locations in Germany during 1991 and 1992. Antibiograms, bacteriophage typing, and plasmid analysis were performed. The antibiograms showed that, besides oxacillin, all CFN ORSA strains were resistant to gentamicin, clindamycin, erythromycin, ciprofloxacin, and fosfomycin. All these isolates were nontypeable with an international set of phages, and an additional experimental phage set indicated that the strains were phage type 16, 192. Moreover, all isolates possessed a single plasmid of 30 kb, and restriction analysis of those plasmids revealed identical patterns. For genotyping, these 50 isolates were also analyzed by pulsed-field gel electrophoresis (PFGE) and polymerase chain reaction (PCR) of the coagulase and protein A genes and then by restriction enzyme digestion and analysis of restriction fragment length polymorphisms (RFLPs). With 49 strains, electrophoresis of SmaI-digested chromosomal DNA revealed identical PFGE patterns regarding the number and size of the DNA fragments, which could be differentiated from those of clumping factor-positive ORSA strains. Typing for the coagulase gene by PCR revealed PCR products of identical sizes. The AluI restriction digestion patterns of the PCR products were identical. PCR with primers derived from the region of that part of the protein A gene that encodes the immunoglobulin G-binding domains showed a PCR product that was about 170 bp smaller than that of the protein A gene from strains that were positive in the protein A latex agglutination test. Since it is precisely this size that is required in order to encode one immunoglobulin G-binding region, we assume that this is not present in the CFN ORSA strains. The phenotypical and genotypical features identify these very unusual CFN ORSA stains as being of clonal origin.

Base Sequence↗

Outbreak of methicillin-resistant Staphylococcus aureus with reduced susceptibility to glycopeptides in a Parisian hospital.

Epidemiological relationships were investigated between 40 methicillin-resistant Staphylococcus aureus (MRSA) strains with decreased glycopeptide susceptibility isolated from November 1998 to March 1999 from 39 patients (17 infected and 22 colonized patients) in nine wards of the Broussais Hospital, Paris, France. Reduced glycopeptide susceptibility was readily detected on brain heart infusion (BHI) agar containing 6 microg of teicoplanin per ml and on gradient plates, but not by the standard disk diffusion method. The MICs of vancomycin and teicoplanin, determined on BHI agar, were 4 and 8 to 32 microg/ml, respectively (standard antibiotic dilution), and 4 to 8 and 8 to 32 microg/ml, respectively (E-test). All strains were resistant to macrolides, aminoglycosides, tetracycline, rifampin, sulfonamides, and pefloxacin, showed reduced susceptibility to fusidic acid and fosfomycin, and were susceptible to trimethoprim and chloramphenicol. Pulsed-field gel electrophoresis and lysotyping revealed that a multidrug-resistant MRSA clone with decreased susceptibility to glycopeptides has been discretely endemic since at least 1996 in our institution, where it was responsible for an outbreak in November and December 1998.

Anti-Bacterial Agents↗

Serological characterisation and antimicrobial susceptibility of Actinobacillus pleuropneumoniae strains isolated from pigs in Spain.

Seventy-one isolates of Actinobacillus pleuropneumoniae isolated from the lungs of pigs in outbreaks of pleuropneumonia in Spain were serotyped by indirect haemagglutination. Serotype 4 (42.2 per cent), serotype 7 (22.5 per cent) and serotype 2 (12.8 per cent) were predominant, whereas serotypes 1, 3, 6, 8, 9, 12 and untypable isolates were present only in small numbers. Serotypes 1, 2, 4 and 7 originated mainly from cases of acute pleuropneumonia, whereas serotypes 3, 6, 8, 9 and 12 were associated with chronically infected herds. The susceptibility of the isolates to 20 antimicrobial agents was determined by agar disc diffusion. Most were susceptible to cefuroxime, cefaclor, cefazolin, kanamycin, tobramycin, gentamicin, oxolinic acid, ciprofloxacin, enoxacin, thiamphenicol, colistin and trimethoprim/sulphamethoxazole. Marked resistance was found with amoxicillin, ticarcillin, oxytetracycline, doxycycline and metronidazole. Rifampicin, fosfomycin and tiamulin were the agents most effective against the isolates tested.

Actinobacillus Infections↗

Epidemic infection caused by Citrobacter rodentium in a gerbil colony.

Non-motile, Gram-negative rods, isolated from the intestinal tract and kidney of several dead animals in a gerbil colony, were identified as Citrobacter rodentium (formerly included in C. freundii species) on the basis of 31 biochemical tests. The isolates were tested against 40 antimicrobial agents and were all susceptible to ticarcillin plus clavulanate, ceftazidime and most of the quinolones studied, but were all resistant to most of the penicillins and aminoglycosides tested, and to fosfomycin, metronidazole and tiamulin. This bacterial species has been primarily associated with transmissible murine colonic hyperplasia, and this appears to be the first report of an epidemic infection in a gerbil colony with a fatal outcome in most of the animals affected.

Animals↗

Pickles, pectin, and penicillin.

My professional life has been devoted to the study of microbial products and their biosynthesis, regulation, and overproduction. These have included primary metabolites (glutamic acid, tryptophan, inosinic acid, guanylic acid, vitamin B(12), riboflavin, pantothenic acid, ethanol, and lactic acid) and secondary metabolites (penicillin, cephalosporins, streptomycin, fosfomycin, gramicidin S, rapamycin, indolmycin, microcin B17, fumagillin, mycotoxins, Monascus pigments, and tetramethylpyrazine). Other areas included microbial nutrition, strain improvement, bioconversions of statins and beta-lactams, sporulation and germination, plasmid stability, gel microdroplets, and the production of double-stranded RNA, the polymer xanthan, and enzymes (polygalacturonase, protease, cellulase). Most of the studies were carried out with me by devoted and hardworking industrial scientists for 15 years at Merck & Co. and by similarly characterized students, postdoctorals, and visiting scientists during my 32 years at the Massachusetts Institute of Technology. I owe much of my success to my mentors from academia and industry. My recent research activities with undergraduate students at the Charles A. Dana Research Institute for Scientists Emeriti (R.I.S.E.) at Drew University have been very rewarding and are allowing me to continue my career.

Anti-Bacterial Agents↗

Genomic Insights Into Multidrug-Resistant Foodborne Serratia liquefaciens Strains Carrying mcr-9 and Comparative Genomic Analysis of Novel Biosynthetic Gene Clusters.

Serratia liquefaciens is an opportunistic nosocomial pathogen with a wide range of antibiotic resistance patterns. This study reports the characterization of the first mcr-9-positive S. liquefaciens strains, 35E-19E1 and CST-066, isolated from meat products in Japan. The strains were screened for the presence of β-lactamases, plasmid-mediated mobile colistin resistance (mcr) genes, and carbapenemase-encoding genes using PCR. Antimicrobial susceptibility was tested using the broth microdilution method. The strains exhibited multidrug resistance (MDR) phenotypes to third-generation cephalosporins, cephamycin, fosfomycin, and other clinically important antimicrobials. Genomic DNA sequencing showed that the genome sizes of CST-066 and 35E-19E1 are 5,529,704 and 5,261,506 bps, respectively. mcr-9 was identified on a chromosome within a genetic environment that included the two-component system qseBC, which plays a key role in the signaling network that triggers colistin resistance in Enterobacterales. Downstream genome analysis revealed a 1695-bp eptB-like kdo2-lipid phosphoethanolamine transferase, which is involved in intrinsic polymyxin resistance mechanisms in Serratia spp. The strain 35E-19E1 carries five CRISPR-Cas enzymes that are essential for adaptive immunity in bacteria, allowing defense against invading elements. Functional analysis using subsystem technology revealed that both strains possess subsystem features responsible for invasion and adhesion within the host biomes. Genome mining using antiSMASH and BAGL4 revealed various biosynthetic gene clusters, responsible for secondary metabolite synthesis. Notably, we identified novel gene clusters, mainly nonribosomal peptide synthetases, in both the strains, indicating their potential to produce bioactive compounds. Although the presence of mcr-9 in Serratia may not be of clinical significance because of natural resistance of the strain to polymyxins, we shed light on the genomic characteristics of this MDR pathogen and the potential spread of mcr-9 among other bacterial species. The emergence of mcr-9 in drug-resistant S. liquefaciens provides significant insights, underscoring the need for increased surveillance of this pathogen.

biosynthetic gene cluster↗

[Susceptibility of vertically transmitted Group B streptococci to antimicrobial agents. Multicenter study].

INTRODUCTION: To investigate the susceptibility of group B streptococci (GBS) to macrolides and lincosamides and assess alternatives for intrapartum chemoprophylaxis in women allergic to penicillin and colonized by a GBS strain resistant to these antibiotics. METHODS: Multicenter study performed with 131 strains isolated between 1997-2002 from newborns diagnosed with early-onset GBS disease and 479 strains collected in 2002 from the vagina or rectum of pregnant women. RESULTS: All the GBS (100%) were susceptible to penicillin, ampicillin, vancomycin, quinupristin/dalfopristin, levofloxacin and teicoplanin. Resistance rates were as follows: 12.45% to erythromycin and azithromycin, 11.80% to clindamycin, 11.31%, to josamycin, 1.80% to telithromycin and 0.32% to fosfomycin. Seventy-nine strains had a constitutive MLSB phenotype of resistance, 4 an inducible MLSB phenotype, 3 an M phenotype and 3 were resistant to clindamycin but susceptible to macrolides. The MIC for erythromycin and azithromycin was > 32 mg/L in more than 85% of GBS strains with a constitutive MLSB phenotype, from 0.5 to 4 mg/L in those with an inducible MLSB, and 4 mg/L in those with phenotype M. Fifty-one telithromycin-sensitive strains (all with a constitutive MLSB phenotype) showed induced resistance to telithromycin when erythromycin was present. No significant differences in antimicrobial resistance were found between GBS strains producing invasive neonatal disease and maternal isolates, or among strains from different geographic areas. CONCLUSIONS: The high rate of resistance to macrolides and lincosamides in our area makes susceptibility testing mandatory for GBS strains isolated from pregnant women allergic to penicillin.

Adult↗

[Changes in the antimicrobial susceptibility of Escherichia coli isolates from nosocomial versus community-acquired urinary tract infections].

INTRODUCTION: We studied the variations in Escherichia coli sensitivity patterns to commonly used antimicrobial agents in urinary tract infections, by stratifying isolates according to year and source. MATERIAL AND METHODS: Retrospective analysis of the sensitivity of 14,319 E. coli urine isolates to 14 antimicrobials during the period of 1994-2001. Sensitivity comparison by source of the isolate began in 1996, and included 13,263 isolates originating in the hospital and 2,350 originating in the community. RESULTS: Penicillins were the least active antibiotic agents against the E. coli isolated (sensitivity 40.9%), followed by cotrimoxazole (66.4%), nalidixic acid (70.8%) and norfloxacin (76.1%). Sensitivities to the other antimicrobials tested remained near 95%. Sensitivity of E. coli isolates to most of the antimicrobials tested decreased gradually during the 8-year period, with a marked decrease for nalidixic acid and norfloxacin (76.0% down to 63.3% and 85.1% down to 66.6%, respectively). Nevertheless, sensitivity of E. coli to nitrofurantoin and ampicillin-sulbactam/amoxicillin-clavulanic acid increased; no significant differences were observed regarding cefazolin, gentamicin and fosfomycin. Sensitivity was higher in community E. coli isolates than in nosocomial isolates. The greatest differences corresponded to cephalosporins (OR = 2), nitrofurantoin (OR = 1.72), and ampicillin-sulbactam/ amoxicillin-clavulanic acid (OR = 1.57). Antimicrobials with significant differences in sensitivity between isolates of different sources decreased gradually from 6 (1996) to 1 (2001). CONCLUSIONS: Penicillins, cotrimoxazole and quinolones can no longer be considered the antimicrobials of choice for empirical treatment of E. coli urinary tract infections. Along the study period, we observed a reduction in the initial susceptibility differences among hospital and community isolates.

Anti-Infective Agents, Urinary↗

[Urinary tract infection in pregnancy].

Urinary tract infections, asymptomatic bacteriuria (AB), acute cystitis (AC) and acute pyelonephritis (AP), are favored by the morphological and functional changes involved in pregnancy. AB increases the risk of preterm labor, low birth weight and AP. AB should be detected by uroculture (other methods are not sufficiently effective) and treated early. Approximately 80% of cases are caused by Escherichia coli. The risks and effectiveness of the distinct antibiotic regimens should be evaluated: fosfomycin trometamol in monotherapy or as short course therapy is safe and effective for the treatment of AB and AC. AP is the most frequent cause of hospital admission for medical reasons in pregnant women and can lead to complications in 10% of cases, putting the lives of the mother and fetus at risk. Currently outpatient treatment of AP is recommended in selected cases. Adequate follow-up of pregnant women with urinary tract infections is required due to frequent recurrence.

Acute Disease↗

Antibiotic susceptibility of Stenotrophomonas (Xanthomonas) maltophilia: comparative (NCCLS criteria) evaluation of antimicrobial drugs with the agar dilution and the agar disk diffusion (Bauer-Kirby) tests.

Ninety-six clinical isolates of Stenotrophomonas maltophilia were examined with the agar dilution method for susceptibility to 19 antimicrobial drugs. Doxycycline, cotrimoxazole, timentin, ofloxacin, fosfomycin, and piperacillin + tazobactam, in that order, inhibited the majority of strains. All isolates were resistant to nitrofurantoin. Concurrent disk susceptibility (Bauer-Kirby method) testing, using currently valid NCCLS interpretative criteria for Pseudomonas aeruginosa, uncovered a significant incidence of very major (category I), major (category II), and minor (categories III and IV) discrepancies for aminoglycosides, cephalosporins, chloramphenicol, and piperacillin + tazobactam and ticarcillin + clavulanic acid. Therefore, new interpretative criteria indicative of intermediate (I) susceptibility of S. maltophilia to these various antibiotics were proposed. In addition, new intermediate susceptibility criteria were proposed for the two beta-lactam-beta-lactamase inhibitor combinations. It was recommended to exclude ciprofloxacin from test batteries against this microorganism due to the wide scatter of minimal inhibitory concentration values and diameters of inhibition zones; the same was true for polymyxin B. It is hoped that the proposed modified, species-specific criteria will improve the clinical utility of laboratory-generated disk antibiograms with respect to the inherently multiple antibiotic-resistant, opportunistic pathogen S. maltophilia.

Anti-Bacterial Agents↗

Antibiotic susceptibility testing (agar disk diffusion and agar dilution) of clinical isolates of Corynebacterium jeikeium.

Thirty-three clinical isolates of Corynebacterium jeikeium were examined for susceptibility to 27 antimicrobial drugs with the agar dilution test. Sheep-blood-supplemented Mueller-Hinton agar performed better than Wilkins-Chalgren agar. Disk susceptibility (Bauer-Kirby) tests were carried out in parallel with 24 of the chemotherapeutic agents. All isolates were susceptible to teicoplanin and vancomycin. All isolates resisted fosfomycin, mupirocin, and trimethoprim-sulfamethoxazole. The isolates varied in susceptibility to ciprofloxacin, doxycycline, fusidic acid, ofloxacin, and tetracycline; most were susceptible to rifampin. Surprisingly few discrepancies between agar dilution and disk diffusion tests were encountered when utilizing NCCLS interpretive criteria currently valid for enterococcal isolates.

Agar↗

Hemoperfusion with polymyxin B-immobilized fiber in septic patients with methicillin-resistant Staphylococcus aureus-associated glomerulonephritis.

BACKGROUND/AIMS: We investigated whether urinary podocytes are present in septic patients with methicillin-resistant Staphylococcus aureus (MRSA)-associated glomerulonephritis and whether polymyxin B-immobilized fiber (PMX-F) treatment affects proteinuria and urinary podocyte excretion in these patients. METHODS: Twenty septic patients with MRSA-associated glomerulonephritis (mean age: 63.7 years) and 80 septic patients whose MRSA infection was not followed by glomerulonephritis (mean age: 60.5 years) were included in this study. All septic patients were treated with fosfomycin sodium, beta-lactams, arbekacin sulfate, and teicoplanin, or a combination of these. Twenty septic patients with MRSA-associated glomerulonephritis were randomly assigned to one of two treatments: PMX-F treatment (group A, n = 10) and conventional treatment (group B, n = 10). PMX-F treatment was repeated twice. RESULTS: Urinary podocytes and urinary protein excretion were not detected in MRSA septic patients without glomerulonephritis. However, urinary podocytes (1.7 +/- 0.6 cells/ml) and proteinuria (2.6 +/- 0.6 g/d) were detected in the 20 septic patients with MRSA-associated glomerulonephritis. Plasma endotoxin levels were decreased from 13.6 +/- 4.6 pg/ml to 6.6 +/- 2.2 pg/ml (p < 0.05) in group A. Levels in group B, however, showed little difference after treatment. Urinary podocytes were reduced in group A (from 1.8 +/- 0.6 cells/ml to 0.4 +/- 0.2 cells/ml, p < 0.01) as was urinary protein excretion (from 3.0 +/- 0.5 g/d to 0.8 +/- 0.4 g/d, p < 0.01) but urinary podocytes and protein excretion levels showed little difference after treatment in group B. CONCLUSION: PMX-F treatment may be effective in reducing urinary protein and urinary podocyte excretion in septic patients with MRSA-associated glomerulonephritis.

Endotoxins↗

Bacteraemia by P. aeruginosa associated with nephrotic syndrome after shunt operation for hydrocephalus.

One patient of sepsis by P. aeruginosa after the implanting of a ventriculoatrial valve following extirpation of an expansive intracranial process is studied. During the evolution of the septic process there appeared as associated nephrotic syndrome with histologic lesions corresponding to an acute exudative glomerular nephritis. The germ became resistant to the antibiotics used, carbenicillin plus gentamicin, being later sensitive only to fosfomycin with which finally complete cure was achieved.

Carbenicillin↗

Simple screening method for gram-positive bacterial beta-lactam antibiotic tolerance on routine laboratory Bauer-Kirby antibiogram plates.

A simple screening method served to detect beta-lactam antibiotic-tolerant variants of clinical isolates and laboratory control strains of staphylococcus aureus, S. epidermis, group B beta-hemolytic streptococci, and Listeria monocytogenes. The beta-lactamase(s) of a multiple drug-resistant strain of Enterobacter cloacae (isolate No. 19) yielded most consistent results as compared with several other beta-lactamase producers; the E. cloacae beta-lactamase(s) was neutralized by clavulanic acid. Spot inocula of E. cloacae isolate No. 19, following overnight "induction" with 1 microgram/ml of ampicillin and 3 microgram/ml of cephalothin in tryptic soya broth, were applied centrally to beta-lactam antibiotic inhibition zones of Bauer-Kirby antibiogram plates (Mueller-Hinton agar, MHA, and diagnostic sensitivity test agar, DSTA) following removal of the appropriate disks. The spot-inoculated plates were incubated overnight at 35 degrees C and inspected for satellite growths of tolerant variants around the E. cloacae spot inocula. Satellite growths of less than or equal to 10 colonies were interpreted to indicate tolerance of the relevant cell wall synthesis inhibitor. The method readily permitted detection of variants tolerant for ampicillin, cephalothin, penicillin G, piperacillin, azlocillin, and mezlocillin. However, strains documented by minimal inhibitory and minimal bactericidal concentrations to be tolerant for cefotaxime, cefoxitin, fosfomycin, and vancomycin only rarely gave rise to respective satellite growths. DSTA proved superior to MHA with respect to "rescue" of inhibited tolerant staphylococcal variants; furthermore, the diameters of inhibition zones obtained on DSTA correlated well with those on MHA. Therefore, DSTA was adopted as the routine test medium for clinical staphylococcal isolates.

Anti-Bacterial Agents↗

In vitro antibiotic susceptibility of Legionellaceae: search for alternative antimicrobial drugs.

Reference strains of Legionella pneumophila (serotypes 1-4, and 6), Legionella micdadei , and Legionella bozemanii proved susceptible (agar dilution test, buffered charcoal yeast extract agar) to erythromycin, rifampin, augmentin (amoxycillin plus clavulanic acid), cefotaxime, cefoxitin, enoxacin , fusidic acid, and norfloxacin; cefamandole was less active. The strains varied in susceptibility to fosfomycin.

Anti-Bacterial Agents↗

Susceptibility of Clostridium perfringens type A to 23 antimicrobial drugs.

A total of 106 strains of Clostridium perfringens type A, that had been isolated very recently from faecal cultures of healthy adults, were examined for susceptibility to 23 antimicrobial drugs (agar dilution method). All strains were susceptible to ampicillin, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftriaxone, ciprofloxacin, fusidic acid, imipenem, metronidazole, mezlocillin, ofloxacin, penicillin G, piperacillin, teicoplanin, and vancomycin. Teicoplanin and imipenem were the most active, whereas fosfomycin and tetracycline were the least active drugs. Three of the 106 strains revealed multiple drug resistance against clindamycin, erythromycin, josamycin, tetracycline, and, in one instance, against chloramphenicol.

Anti-Bacterial Agents↗

Susceptibility of Bordetella pertussis and Bordetella parapertussis to 24 antibiotics.

The susceptibility of Bordetella pertussis (28 strains) and Bordetella parapertussis (6 strains) to 24 antibiotics (penicillin and cephalosporin derivatives, erythromycin, josamycin, cotrimoxazole, imipenem, aztreonam and fosfomycin) was studied by means of the agar dilution method using charcoal horse blood agar. Piperacillin and mezlocillin showed the highest activity (MIC 0.0039-0.00781 micrograms/ml) against B. pertussis while B. parapertussis was most susceptible to piperacillin (0.03125-0.0625 microgram/ml), mezlocillin and latamoxef (0.125-0.25 microgram/ml).

Anti-Bacterial Agents↗