Polyarticular septic arthritis.

Twenty-five cases of polyarticular septic arthritis (PASA) were observed in our department over a 13-year period. They accounted for 16.6% of all septic arthritis (15% on average in the literature). A male predominance was noted in our patients, as well as in the literature. The knee was the most frequent location followed by the elbow, shoulder, and hip, in varying order depending on the series. An average of 4 joints was involved. The causative microorganism was Staphylococcus aureus in 20/25 of our patients and in about 50% of published cases. Other frequently causative organisms were streptococci and gram-negative bacteria. Blood cultures and joint aspirations were positive in 19/22 and 23/25 of our cases, respectively. Other septic lesions were noted in 10/25 of our cases. Fever and severe leukocytosis were absent at admission in 5/25 (literature, 37%) and 10/25 of our 25 patients, respectively. The underlying disease was rheumatoid arthritis in 13/25, while 9 of the other patients had immunodepression caused by drugs or by concurrent illness. Typically, rheumatoid arthritis was long-standing and erosive, patients having ulcerated calluses on the feet. This skin source was also noted in 23/36 published cases of PASA in rheumatoid arthritis. Systemic lupus erythematosus was an uncommon disease in PASA, but its presence promoted gram-negative infection. Despite effective therapy with 2 antibiotics, 8/25 patients died, a prognosis that is equally severe in cases reported in the literature (30%) and one that has remained surprisingly stable over the last 40 years. For comparison, the death rate was only 4% in our patients with MASA. Factors contributing to a poor prognosis were age greater than 50 years, rheumatoid arthritis as an underlying disease, and disease of staphylococcal origin. Septic polyarthritis should be considered even when the clinical picture is not florid--when patients have low fever and normal white blood cell counts. Nor should the simultaneous involvement of distant joints rule out infection. Indeed, the frequency of underlying rheumatic disease and its treatment may further confuse the clinical presentation. Joints suspected of harboring infection should be aspirated, including those previously affected by the concurrent rheumatism.

Selective digestive decontamination by erythromycin-base in a polyvalent intensive care unit.

OBJECTIVE: To study the effect of selective digestive tract decontamination by erythromycin-base on the incidence of carriage and infection with MR Enterobacteriaceae producing an extended spectrum beta-lactamase (ESB). DESIGN: After a 10-week prospective survey to ascertain the baseline incidence in two bays (1 and 3) of the same ICU, bay 1 was compared with bay 3 during a further survey of 6 months. The patients in bay 1 received erythromycin-base. SETTING: Two non-contiguous bays, 1 and 3, of 4 beds, in the same polyvalent ICU of a university hospital. PATIENT: Consecutive patients with unit stay longer than 2 days; 34 patients were included during the control period, 43 in bay 1 (decontamination) and 46 in bay 3 (control) during the trial period. INTERVENTION: Erythromycin-base, 1 g t.i.d. in powder form administered by gastric tube to patients in bay 1 from admission to discharge. MEASUREMENTS AND RESULTS: Digestive tract carriage was monitored by cultures of gastric and rectal swab specimens, sampled twice a week. Enterobacteriaceae were isolated on Drigalski agar with incorporated ceftazidime (4 mg/l). In bay 1 there was a decrease in ESB producing Enterobacteriaceae (23% vs 10%, p = 0.0004) from rectal swab, especially in K. pneumoniae (15% vs 2%, p = 10(-5)), during the decontamination period in comparison to the control period. During the trial period the only differences observed between bays 1 and 3 were in the gastric samples: K. pneumoniae were less often isolated in bay 1 than in bay 3 (0% vs 3%, p = 0.03). Intestinal carriage with multiresistant Enterobacteriaceae occurred in 28% patients in bay 1 and 30% patients in bay 3 during the trial period (p = 0.79). Erythromycin-base did not delay the carriage by patients in bay 1 (log rank test p = 0.42). CONCLUSION: Erythromycin-base was not effective in preventing digestive tract carriage due to Enterobacteriaceae resistant to third generation cephalosporin by production of chromosomal cephalosporinase. The decrease in isolates containing K. pneumoniae in bay 1 cannot be definitively attributed to erythromycin-base, since the number of this species in bay 3 was low.

Susceptibility of Enterobacteriaceae to beta-lactam agents and fluoroquinolones: a 3-year survey in France.

OBJECTIVE: To assess trends in the susceptibility to beta-lactam agents and to fluoroquinolones of clinically relevant Enterobacteriaceae isolated over a 3-year period in 14 French hospital laboratories. METHODS: During the second quarter of 1996, 1997 and 1998, 180 consecutive non-duplicate isolates of Enterobacteriaceae were collected in each center. Sixteen beta-lactams and four quinolones were tested by the disk diffusion method. In addition, the double-disk synergy test was used to screen for the production of extended-spectrum beta-lactamase (ESBL). RESULTS: Totals of 2507, 2312 and 2506 clinical isolates were obtained in each period, respectively. The distribution of Enterobacteriaceae species according to clinical specimens and wards was similar in each study period. No significant variation in the susceptibility rates to beta-lactams and fluoroquinolones was observed, except in Klebsiella pneumoniae and Enterobacter aerogenes. The prevalence of ESBL-producing isolates decreased from 18% to 9% in the former, while it increased from 32% to 54% in the latter. At the same time, the susceptibility to ofloxacin and pefloxacin increased for K. pneumoniae (P < 0.003) and cephalosporinase-producing species (P < 0.05), except Enterobacter spp. CONCLUSION: Over the 3-year study period beta-lactams and fluoroquinolones remained highly active against Enterobacteriaceae clinical isolates, with the exception of E. aerogenes, probably as a result of the dissemination of multiresistant clones in French hospitals.

Clinical and bacteriological survey after change in aminoglycoside treatment to control an epidemic of Enterobacter cloacae.

The effect of a change in the first line antibiotic treatment in a neonatal unit was studied. A total of 238 neonates (G1), admitted between 1 January and 31 July 1989, and treated with gentamicin, were compared with 398 (G2) admitted between 1 August 1989 and 31 July 1990 who received amikacin, in the combination of ampicillin plus an aminoglycoside. This change was implemented in an attempt to prevent the spread of an epidemic strain of Enterobacter cloacae resistant to third generation cephalosporins and all aminoglycosides, except amikacin. The change in treatment had no effect on the incidence of nosocomial infections [19.7% (G1) vs. 16.3% (G2) RR = 1.21 (0.86-1.70)], but the proportion of patients with nosocomial infections caused by the E. cloacae decreased (6.3% vs. 2.0% RR 3.14 CI 1.35-7.28). Certain trends in the bacterial ecology emerged: E. aerogenes and Enterococci increased in G2. The proportion of gentamicin-resistant strains such as E. cloacae or Staphylococci decreased and there was no increase in aminoglycoside-resistant strains, except in Escherichia coli, in which resistance to amikacin rose from 0 to 3%. This study illustrates the influence of antimicrobial therapy on the species and the resistance of strains isolated in nosocomial infections. It also highlights the need for epidemiologic surveillance, and poses the question of how best to modify antibiotic policy.

A case-control study of an outbreak of infections caused by Klebsiella pneumoniae strains producing CTX-1 (TEM-3) beta-lactamase.

In July 1984 Klebsiella pneumoniae producing beta-lactamase CTX-1(TEM-3) (K. pneumoniae-CTX-1) spread from an Intensive Care Unit (ICU) throughout the hospitals of Clermont-Ferrand, France, and were isolated in four other hospitals of the region. A retrospective case control study was conducted in the ICU to characterize the risk factors for nosocomial infection with this organism. The cases were the 74 patients who had had K. pneumoniae-CTX-1 isolated from one or more clinical samples between July 1984 and December 1987. They were compared with 74 controls for host risk factors, underlying disease, procedures and antibiotic treatment. The monthly incidence of infection/colonization varied from 0% to 14.6%. The mortality rate attributable to this organism was 0.26% during the study period. The duration of stay of cases was longer than that of controls. More cases than controls had ventilatory assistance. However, the predominant risk factor was emergency abdominal surgery. Before K. pneumoniae-CTX-1 was isolated, cases received quinolones and trimethoprim sulphamethoxazole more often than controls. However, only 15% of cases had received third generation cephalosporins while at the onset of K. pneumoniae-CTX-1 infection colonization, 32 patients were no longer being given antibiotics. The use of antibiotic prophylaxis by, for example, selective digestive tract decontamination should be considered in patients at high risk of infection.

Role of infection control measures in limiting morbidity associated with multi-resistant organisms in critically ill patients.

A retrospective comparative study was performed to determine the impact of infection control measures (ICMs) on colonization and infections due to methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae (producing transferable extended-spectrum beta-lactamase, KPESBL), and multi-resistant Enterobacter aerogenes (MREA) in intensive care unit patients. Infection Control Measures included surveillance cultures, isolation procedures and mupirocin for MRSA nasal carriage. The numbers of patients infected and/or colonized by MRSA, KPESBL or MREA were compared during two consecutive one-year periods (Period 1 before ICMs, and Period 2 after ICMs). The antibiotic consumption during the two periods was analysed. In Period 1 and Period 2, respectively, the rate of patients infected or colonized by at least one of the three organisms was 15% and 6.8% (P=0.001); by MRSA 7.7% and 2.6% (P=0. 004); by KPESBL 1.7% and 0% (P=0.25); and by MREA 5.6% and 4.3% (P=0. 47). During Period 2, there was a clear-cut decrease in the percentage of patients infected by MRSA (P=0.018), a non-significant decrease in those infected by KPESBL (P=0.06), and no decrease in patients infected by MREA (P=0.22). When calculated per 1000 patient-days, for Period 1 and Period 2, respectively, the rate of patients infected or colonized by at least one of the three organisms was 11.9 and 8.8; for MRSA it was 4 and 2.2; for KPESBL it was 1 and 0; and for MREA it was 4 and 4. Antibiotic cost was pound98.7 in Period 1 and pound62.7 in Period 2. ICMs contributed to the control of infections and colonizations due to MRSA and KPESBL but not those due to MREA.

The kinetics of CAZ-5, a novel SHV-related plasmid-mediated beta-lactamase with enhanced hydrolytic activity against ceftazidime.

The kinetic constants for "CAZ-5", a novel plasmid-mediated beta-lactamase with noticeable activity against third-generation cephalosporins and particularly ceftazidime have been determined. Two closely-related plasmid-mediated beta-lactamases have also been studied: SHV-2 and PIT-2 (also known as SHV-1). These enzymes were synthesized constitutively; they were highly sensitive to the action of the inhibitors clavulanic acid and sulbactam and they lacked activity against the cephamycins and imipenem. PIT-2/SHV-1 had poor hydrolytic activity against the third-generation cephalosporins, SHV-2 was markedly active against cefotaxime and related compounds, whereas the new enzyme, which was also active against these cephalosporins, had a noticeably greater activity against ceftazidime. Aztreonam was slowly hydrolysed by CAZ-5 beta-lactamase, but demonstrated an unusually high affinity for this enzyme.

The kinetics of SHV-2 plasmid-mediated beta-lactamase compared to those of the parent enzyme from which it is derived.

Kinetic constants were determined for two closely related plasmid-mediated beta-lactamases: SHV-2 and PIT-2 (also known as SHV-1). These enzymes were synthesized constitutively. They were highly sensitive to the action of the inhibitors clavulanic acid and sulbactam, and they lacked activity against cephamycins and also imipenem. Both enzymes were significantly active against penicillins and first-generation cephalosporins, and the main difference concerned the third-generation cephalosporins: SHV-2 was highly active against these compounds whereas PIT-2 was not.

Differences between clavulanic acid and sulbactam in induction and inhibition of cephalosporinases in enterobacteria.

The ability of clavulanic acid and sulbactam to induce and inhibit cephalosporinases was evaluated in 16 clinical isolates of enterobacteria. Using the quantitative induction assay, the checkerboard method and the disc approximation test, clavulanic acid was shown to act as inducer for all species, whereas sulbactam only induced strains of Providencia stuartii. Antagonism was achieved using a combination of clavulanic acid and cefotaxime but a combination of sulbactam and cefotaxime was either synergistic or indifferent. This variation in effect was probably due to the fact that sulbactam, but not clavulanic acid could inhibit cephalosporinases. The data revealed a significant difference between sulbactam and clavulanic acid, which may have relevance to their relative usefulness in combination with beta-lactam antibiotics for the treatment of infections due to enterobacteria that produce inducible cephalosporinase.

Resistance to beta-lactams in Enterobacteriaceae: distribution of phenotypes related to beta-lactamase production.

Phenotypes of susceptibility to amoxycillin (Amo), ticarcillin (Tic), cephalothin (Ctn) were determined in 1366 isolates of Enterobacteriaceae by disk method and beta-lactamases were identified in 243 strains belonging to different phenotypes of amoxycillin-resistant strains. AmoR TicR CtnS strains (25%) were penicillinase producers and all of them were susceptible to the combination amoxycillin/clavulanic acid (Amo/CA) and ticarcillin/clavulanic acid (Tic/CA). Amo1/R TicS CtnR strains (12%) were cephalosporinase producers and resistance to Amo/CA was observed, except for Proteus vulgaris. AmoR TicR CtnR strains (18%) often produced two beta-lactamases (penicillinase and cephalosporinase) and they were resistant to Amo/CA; in this group, susceptibility to Tic/CA depends on the nature and the amount of the beta-lactamase produced, except for Serratia marcescens for which antibiotic resistance is probably due to other mechanisms. Tic/CA resistance was mainly found in Serratia marcescens (41%) and Enterobacter cloacae (36%).

Pharmacokinetics of cefotaxime and its desacetyl metabolite in plasma and in cerebrospinal fluid.

The aim of the study was to investigate the pharmacokinetic modelling of Cefotaxime (CTX) and its main metabolite Desacetyl Cefotaxime (DCTX) which has a less antibacterial activity than the CTX. After intravenous administration of 1g of CTX to 26 patients, the plasma concentrations determined by HPLC showed that the pharmacokinetics of CTX and transformation to DCTX can be described with an open five-compartment model. The implications of this are discussed from the clinical point of view.

[Verotoxin-producing Escherichia coli infections: study of its prevalence in children in the Auvergne region]. / Les infections à Escherichia coli producteurs de vérotoxines: étude de la prévalence chez l'enfant dans la région Auvergne.

Verotoxin producing Escherichia coli (VTEC) have been associated with disease outbreaks of diarrhea hemorrhagic colitis and hemolytic-uremic syndrome in humans. Contamination occurs mainly by ingestion of beef and dairy products, but water and person to person transmission have also been described. Most of the clinical signs are due to the production of Stx1 and/or Stx2 Shiga toxins, also called verotoxins. Other virulence factors include enterohemolysin, and the product of the eae gene, intimin, involved in the attaching and effacing adherence phenotype. The predominant serotype is O157:H7, but VTEC strains of more than one hundred serotypes can cause human disease. In order to determine the prevalence of VTEC infections among children in the central part of France, stool samples from hospitalized children were examined for stx1 and stx2 genes by using a polymerase chain reaction (PCR) technique. From October 1997 to September 1998, 658 stool samples were analysed: among them 19 (3%) were stx-PCR positive. Only 8 children out of 19 had diarrhea, and for 5 of them, an enteric pathogen other than VTEC was isolated. VTEC strains were isolated from 10 samples: most of the isolates did not produce verotoxins at a high level, and they did not belong to serotypes associated with pathogenicity, which might explain the absence of relationship between VTEC isolation and pathogenicity in our study.

[In vitro comparative study of piperacillin-aminoglycosides combinations against Enterococci and Enterobacteriaceae]. / Etude comparative in vitro d'associations pipéracilline-aminosides face aux entérocoques et aux entérobactéries.

The hundred and ninety-two combinations were tested against 17 strains chosen from the results of MIC determination (disc method): 5 enterococci exhibiting low level resistance (r) or high level resistance (R) to streptomycin (S) and gentamicin (G): 2 strains Sr Gr, 2 strains SR Gr and 1 strain Sr GR; 12 enterobacteria chosen for their resistance phenotypes to beta-lactams and aminoglycosides and because they are the most frequent clinical isolates: 2 strains Amos Tics Ctns (group 1), 4 strains AmoR Tics CtnR (gr. II), 4 strains AmoR TicR Ctns (gr. III) and 2 strains AmoR TicR CtnR (gr. IV). MIC and MBC were assessed for the 17 strains (Mueller Hinton broth). Combinations were carried out by a checkerboard micromethod. FBC index was calculated for each combination. Against enterococci the 50 combinations were: piperacillin versus ampicillin + aminoglycosides (streptomycin, tobramycin, amikacin, gentamicin, netilmicin). Against enterobacteria piperacillin was combined with different aminoglycosides depending on their resistance phenotypes. These combinations were compared with ticarcillin or mezlocillin or cefotaxime + aminoglycosides (total number 142). The species studied produced different results: with the enterococci Gr synergistic effects (FBC = 0.62-0.75) were rare; additive and indifferent effects were predominant. With the GR strain some antagonistic effects were observed. With the enterobacteria, in groups I and II synergistic effects were frequent and almost equivalent regardless of the beta-lactam chosen. In groups III and IV (TicR) piperacillin MICs were greater than or equal to 128 mg/l and mezlocillin MICs greater than 512 mg/l; the synergistic effects were significant (FBC from 0.25 to 0.62). beta-lactam + amikacin or netilmicin, and especially piperacillin + amikacin, were found to have the most frequent synergistic effects upon the strains tested. Mezlocillin combinations cannot be used clinically; the use of piperacillin combinations requires further discussion. On the other hand, cefotaxime + aminoglycosides combinations are active against those TicR strains.

[Haemophilus parainfluenzae meningitis in an 8-year-old boy]. / Méningite à Haemophilus parainfluenzae chez un enfant de 8 ans.

Invasive infections caused by Haemophilus parainfluenzae, a saprophyte of the respiratory tract, are exceptional and should arise suspicion of abnormalities in immunocompetence. So far, about thirty cases of H. parainfluenzae meningitis affecting neonates, infants or adults have been published. A case of such meningitis in an 8-year old boy without any risk factor is reported here.

[Value of puncture-arthrography in the diagnosis of infection of total hip arthroplasty]. / Intérêt de la ponction-arthrographie de hanche dans le diagnostic d'infection sur prothèse totale.

Arthrography with hip aspiration was performed in 143 patients with hip arthroplasties to determine its effectiveness as a technique for diagnosing infection. Thirty-three cases of infection were found. On 26 occasions the germ responsible was isolated in the joint fluid. In six other cases infection was revealed from cytologic or arthrographic findings, or from both. Only once was a diagnosis of infection not arrived at. In this series of patients, except in cases of evolutive inflammatory rheumatism, cytologic examination of the joint fluid was a discriminative factor in diagnosis. Hip aspiration arthrography had a sensitivity of 79 per cent for the diagnosis of infection in arthroplasty with isolation of the germ and a specificity of 100 per cent. The sensitivity of the diagnosis rose to 91% when any one of the following features was observed: leucocytosis of the joint fluid higher than 10,000 elements/mm3; presence of a fistula or of fistulization on arthrography; isolation of the germ in the joint fluid or the rinsing liquid.

[VCA agar (bioMérieux) for selective isolation of vancomycin-resistant Enterococci (VRE) from fecal specimens]. / Utilisation de la gélose VCA3 (bioMérieux) pour l'isolement sélectif des Enterococci résistants à la vancomycine à partir de prélèvements fécaux.

Screening for Vancomycin Resistant Enterococci (VRE) is recommended for preventing nosocomial infections with VRE. The aim of this study was to assess the performance of VCA3 agar (bioMérieux) in VRE isolation from fecal specimens. 220 specimens were cultured on VCA3 agar, which contains vancomycin and in parallel, on CAP agar (Oxoid), which is vancomycin-free. 36 vancomycin resistant enterococci were isolated: 24 isolates of Enterococcus faecium expressed a high-level resistance to vancomycin and 12 isolates of E. gallinarum/casseliflavus exhibited resistance at low-level. The sensitivity of VCA3 appeared greater than that of CAP for VRE isolation: 92% (22/24) vs 79% (19/24) for E. faecium (NS, P>0.05) ; 83% (10/12) vs 50% (6/12) for E. gallinarum/casselliflavus (NS, P>0.05). As expected, initial cultures of multiple gram positive organisms were far more frequent on CAP agar than on VCA3 agar. The isolation rate of vancomycin susceptible gram positive strains was impressively lower on VCA3 medium than on CAP medium. VCA3 agar avoided therefore additional subcultures, useless identification and susceptibility tests. In conclusion, VCA3 medium could be useful for the direct, rapid and selective isolation of VRE from fecal specimens.

TEM-109 (CMT-5), a natural complex mutant of TEM-1 beta-lactamase combining the amino acid substitutions of TEM-6 and TEM-33 (IRT-5).

Escherichia coli CF349 exhibited a complex beta-lactam resistance phenotype, including resistance to amoxicillin and ticarcillin alone and in combination with clavulanate and to some extended-spectrum cephalosporins. The double-disk synergy test was positive. CF349 harbored an 85-kb conjugative plasmid which encoded a beta-lactamase of pI 5.9. The corresponding bla gene was identified by PCR and sequencing as a bla(TEM) gene. The deduced protein sequence revealed a new complex mutant of TEM-1 beta-lactamase designated TEM-109 (CMT-5). TEM-109 contained both the substitutions Glu104Lys and Arg164His of the expanded-spectrum beta-lactamase (ESBL) TEM-6 and Met69Leu of the inhibitor-resistant TEM-33 (IRT-5). TEM-109 exhibited hydrolytic activity against ceftazidime similar to that of TEM-6 (k(cat), 56 s(-1) and 105 s(-1), respectively; K(m) values, 226 and 247 microM, respectively). The 50% inhibitory concentrations of clavulanate and tazobactam (0.13 microM and 0.27 microM, respectively) were 5- to 10-fold higher for TEM-109 than for TEM-6 (0.01 and 0.06 microM, respectively) but were almost 10-fold lower than those for TEM-33. The characterization of this novel CMT, which exhibits a low level of resistance to inhibitors, highlights the emergence of this new ESBL type.

[Role of Chlamydiae in genital infections in man]. / La place des chlamydiae dans les infections génitales chez l'homme.

The importance of the part played by Chlamydia trachomatis in male genital infections has only become apparent in recent years. In man, this bacteria is the main agent responsible for non-gonococcal urethritis and for at least 30% of the cases of acute epididymitis in adults. Although bacteriologically difficult, its identification is of great practical use, because of the hypersensitiveness of Chlamydia to tetracyclines.