Fighting the spread of AmpC-hyperproducing Enterobacteriaceae: beneficial effect of replacing ceftriaxone with cefotaxime.

OBJECTIVES: Considering the hypothesis that the high biliary elimination of ceftriaxone could be responsible for the selection of Enterobacteriaceae harbouring high-level AmpC ß-lactamase (HL-CASE), the use of ceftriaxone was discontinued in our hospital in 2006 and replaced with cefotaxime. METHODS: Antibiotic consumption, expressed as defined daily dose (DDD)/1000 patient-days (PD), and HL-CASE incidence, expressed as the number of patients carrying HL-CASE/1000 PD, were compared between the pre-intervention period (Period 1, 2001-05) and the post-intervention period (Period 2, 2006-12) using an interrupted time series analysis. RESULTS: The incidence of HL-CASE increased significantly from 0.32 to 0.69/1000 PD during Period 1 (coefficient = 0.082, P < 0.01). A significant inflection of the slope in the incidence curve occurred in Period 2 (coefficient = -0.061, P = 0.05), mainly owing to the stabilization of the HL-CASE incidence of Enterobacteriaceae harbouring chromosomally inducible cephalosporinase (Period 1, 0.27 to 0.64/1000 PD; Period 2, 0.58 to 0.61/1000 PD) and especially for Enterobacter cloacae (Period 1, 0.09 to 0.30/1000 PD; Period 2, 0.26 to 0.27/1000 PD). This deceleration was observed despite a significant increase in the slope of cefotaxime consumption over Period 2 (coefficient = 2.97, P < 0.01). CONCLUSION: Despite the disadvantages of using cefotaxime compared with ceftriaxone (administration three times daily versus once a day), the ecological benefits of this substitution seem sufficiently convincing to preferentially use cefotaxime. Control of HL-CASE incidence is crucial to limiting carbapenem use and preventing the selection of carbapenemase-producing Enterobacteriaceae.

Comparison of five media for detection of extended-spectrum Beta-lactamase by use of the wasp instrument for automated specimen processing.

Overall, 2,337 rectal screening samples (RSSs) were seeded by using the Wasp instrument for automated microbiological processing with five media for detection of extended-spectrum ß-lactamase (ESBL): CHROMagar, ChromID, Brilliance, BD Drigalski, and HEGP media. Of 354 RSSs harboring ESBL-producing isolates, 89.3% were found to be positive on all media. Sensitivity and specificity ranged from 95.5 to 98.3% and from 57.9 to 72.3%, respectively. No medium was perfectly ESBL selective, and non-ESBL-producing strains were mainly Enterobacteriaceae overproducing AmpC ß-lactamase and nonfermenting Gram-negative bacilli, mostly Pseudomonas aeruginosa.

Readmission of known MRSA carriers and MRSA colonization pressure in hospital.

Readmission of asymptomatic methicillin-resistant Staphylococcus aureus (MRSA) carriers may contribute to the hospital reservoir. Using an electronic alert system, we assessed the weight of readmission of known MRSA carriers on MRSA colonization pressure in a hospital setting. During the 2004-2010 period, 2058 alerts were generated for 1060 inpatients. A total of 486/1060 patients (46%) were readmitted at least once, and 330/486 (64·4%) were readmitted <3 months after discharge. A mean of 20 MRSA patients were present on the same day (from 40 in 2004 to eight in 2010). The number of MRSA patient-days was 34 575, i.e. 2·5% of the 1 366 277 patient-days of the study period, and 17 737 (51·3%) MRSA patient-days were due to readmission of known MRSA carriers. The number of new MRSA cases was partly correlated with the number of MRSA patients hospitalized (R 2 = 0·49). Rapid electronic identification of these patients proved essential in decreasing the global burden of MRSA in our hospital.

Impact of infant pneumococcal vaccination on invasive pneumococcal diseases in France, 2001-2006.

Vaccination with the 7-valent pneumococcal conjugate vaccine (PCV) has been recommended in France since 2003 for children under the age of two years who are at risk due to medical or living conditions. From 2006, the recommendation has been extended to all children under two years. The impact of PCV introduction on the incidence of pneumococcal meningitis and bacteraemia and on the serotype distribution in French children and other age-groups was assessed using laboratory surveillance data. The coverage with three doses of PCV was 44% in children aged 6-12 months in 2006. From 2001/2002 to 2006, the incidence of pneumococcal meningitis decreased from 8.0 to 6.0 cases per 100,000, and the incidence of pneumococcal bacteraemia decreased from 21.8 to 17.5 cases per 100,000 in children under the age of two years. For the vaccine strains, the incidence of pneumococcal meningitis and bacteraemia decreased from 20,4 to 6.0 cases per 100,000, while the incidence of pneumococcal meningitis and bacteraemia due to non-vaccine strains increased from 9.4 to 17.5 cases per 100,000 in this time period. The incidence in older children and adults did not decrease. Further expansion of PCV coverage is expected to increase the impact of the vaccination in both children and adults. However, the fact that cases caused by vaccine serotypes have been partially substituted by cases of non-vaccine serotypes is likely to reduce the overall benefit of PCV in France, should this early observation be confirmed in the future.

Occurrence of qnrA-positive clinical isolates in French teaching hospitals during 2002-2005.

Bacteria harbouring the novel qnrA plasmid-mediated mechanism of quinolone resistance have been described in different countries, but the frequency of their occurrence has not been investigated. In total, 1,468 clinical isolates of Enterobacteriaceae with quinolone resistance or extended-spectrum beta-lactamase (ESBL) phenotypes were collected from eight teaching hospitals in France during 2002-2005 and screened for qnrA. Overall, 28 isolates (22 Enterobacter cloacae, three Klebsiella pneumoniae, one Citrobacter freundii, one Klebsiella oxytoca and one Proteus mirabilis) were positive for qnrA, representing 1.9% of all isolates, 3.3% of ESBL-producing isolates (22% of the E. cloacae isolates) and 0% of non-ESBL-producing isolates. The prevalence of qnrA among consecutive ESBL-producing isolates in 2004 from the eight hospitals was 2.8% (18/639). Of the qnrA-positive isolates, 100% were intermediately-resistant or resistant to nalidixic acid, and 75% to ciprofloxacin. Twenty-one of the 22 qnrA-positive E. cloacae isolates were obtained from two hospitals in the Paris area, and molecular typing and plasmid content analysis showed clonal relationships for five, three and two isolates, respectively. The qnrA genetic environment was similar to that of the In36 integron. The remaining two isolates had qnrA variants (30 and 29 nucleotide differences, respectively, compared with the original sequence) and an unknown genetic environment. The ESBL gene associated with qnrA was bla(SHV-12) in most of the isolates, but bla(PER-1) and bla(SHV-2a) were found in two isolates. In France, it appears that qnrA-positive isolates are predominantly E. cloacae isolates producing SHV-12, and may be associated with the dissemination of an In36-like integron.

Muscle involvement in the scleroderma syndromes.

Muscle involvement was identified in 14 patients with scleroderma or a connective tissue disease overlap syndrome with predominant features of scleroderma. Patients presented with symmetrical proximal weakness indistinguishable from other inflammatory myopathies. Creatine kinase and electromyography were useful to demonstrate muscle involvement. Muscle histopathology demonstrated primarily the vasculopathy of scleroderma or polymyositis in similar numbers of patients. Scleroderma vasculopathy and polymyositis generally occur without specificity to diffuse scleroderma, the calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia syndrome, or an overlap syndrome with arthritis. Polymyositis also occurs when the vasculopathy of scleroderma involves other organ systems.

Impact of the pneumococcal conjugate vaccines on invasive pneumococcal disease in France, 2001-2012.

CONTEXT AND AIMS: Vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) was recommended in France in 2003 for children <2 years. The 13-valent conjugate vaccine (PCV13) replaced PCV7 in 2010. We assessed the impact of PCVs vaccination on the incidence of invasive pneumococcal diseases (IPD) in French children (0-15 years) and adults (>15 years). METHODS: IPD rates were calculated using cases reported from 2001 to 2012 to Epibac, a laboratory network. The distribution of serotypes was assessed from invasive isolates serotyped at the National reference Centre for Pneumococci. IPD incidence rates were compared between the pre-PCV7 (2001-2002), late PCV7 (2008-2009) and post PCV13 (2012) periods. RESULTS: The PCVs coverage increased from 56% in the 2004 birth-cohort to 94% in the 2008 and following birth-cohorts. Following PCV7 introduction, IPD incidence decreased by 19% between 2001-2002 and 2008-2009 in children <2 years, but increased in children aged 2-15 years and adults, despite a sharp decline in PCV7-IPD in all age-groups. After PCV13 introduction, IPD incidence decreased by 34% in children <5 years, by 50% in those aged 5-15 years and 15% in adults from 2008-2009 to 2012. The incidence of PCV13-Non PCV7-IPD decreased by 74% in children <5 years and by 60% in those aged 5-15 years. CONCLUSIONS: Vaccination with PCV13 was rapidly followed by a decrease in the incidence of all-type IPD in children, in relation with a sharp decrease in the incidence of PCV13-Non PCV7-IPD. Moreover, all-type IPD decreased after PCV13 introduction in older non-vaccinated age-groups, with a shift in the distribution of serotypes. Considering the whole 2001-2012 period, the vaccination with PCV7 and PCV13 resulted in a decline in the incidence of IPD in children up to the age of 5 but not in older children and adults.

Decline in antibiotic resistance and changes in the serotype distribution of Streptococcus pneumoniae isolates from children with acute otitis media; a 2001-2011 survey by the French Pneumococcal Network.

Streptococcus pneumoniae is an important cause of acute otitis media (AOM). The aim of this study was to evaluate trends in antibiotic resistance and circulating serotypes of pneumococci isolated from middle ear fluid of French children with AOM during the period 2001-2011, before and after the introduction of the PCV-7 (2003) and PCV-13 (2010) vaccines. Between 2001 and 2011 the French pneumococcal surveillance network analysed the antibiotic susceptibility of 6683 S. pneumoniae isolated from children with AOM, of which 1569 were serotyped. We observed a significant overall increase in antibiotic susceptibility. Respective resistance (I+R) rates in 2001 and 2011 were 76.9% and 57.3% for penicillin, 43.0% and 29.8% for amoxicillin, and 28.6% and 13.0% for cefotaxime. We also found a marked reduction in vaccine serotypes after PCV-7 implementation, from 63.0% in 2001 to 13.2% in 2011, while the incidence of the additional six serotypes included in PCV-13 increased during the same period, with a particularly high proportion of 19A isolates. The proportion of some non-PCV-13 serotypes also increased between 2001 and 2011, especially 15A and 23A. Before PCV-7 implementation, most (70.8%) penicillin non-susceptible pneumococci belonged to PCV-7 serotypes, whereas in 2011, 56.8% of penicillin non-susceptible pneumococci belonged to serotype 19A. Between 2001 and 2011, antibiotic resistance among pneumococci responsible for AOM in France fell markedly, and PCV-7 serotypes were replaced by non-PCV-7 serotypes, especially 19A. We are continuing to assess the impact of PCV-13, introduced in France in 2010, on pneumococcal serotype circulation and antibiotic resistance.

Polyneuropathy due to acute arsenic intoxication: biopsy studies.

A 41-year-old vintner attempting suicide ingested 8-9 g of arsenic and developed a symmetric polyneuropathy with acute Wallerian degeneration of myelinated fibers. Under treatment with modified British Anti-Lewisite (BAL; "Dimaval") his polyneuropathy slowly, but incompletely, subsided over three years at which time another sural nerve biopsy specimen showed regenerative proliferation of myelinated and unmyelinated axons but no signs of Wallerian degeneration. By laser microprobe mass analysis (LAMMA) arsenic was located in the first biopsied sural nerve specimen but not in the second specimen. These findings demonstrated: 1) arsenic induced serial morphometric and electron microscopic findings of nerve fiber degeneration and regeneration, 2) documentation of arsenic within myelinated nerve fibers, and 3) the usefulness of the LAMMA technique as a diagnostic procedure in this context.

Substitution of serine for arginine in position 162 of TEM-type beta-lactamases extends the substrate profile of mutant enzymes, TEM-7 and TEM-101, to ceftazidime and aztreonam.

TEM-7 is a novel broad-spectrum beta-lactamase (Bla), selected in vivo, with a resistance profile similar to that of TEM-1 and TEM-2, but extended to ceftazidime (Caz) and aztreonam. Nucleotide sequencing revealed that the TEM-7 gene is almost identical with that of TEM-2. There was 1 bp change which would result in the substitution of Ser (TEM-7) for Arg (TEM-2) in amino acid (aa) position 162 (i.e., aa position 139 of the mature enzyme). This substitution, also found in TEM-101, a spontaneous in vitro derivative of TEM-1 selected on Caz, was assumed to be responsible for the extension of the substrate profile. The assumption was verified by exchange of a DNA fragment, carrying the mutation of the TEM-7-coding gene, with the homologous fragment of the TEM-1-coding gene in pBR322. In the three-dimensional model of class-A Bla [Joris et al., Biochem. J. 250 (1988) 313-324], aa 139 is located at the rim of the groove which contains the active center and adjacent to the evolutionarily conserved BoxV. It is speculated that extra free hydroxyl groups in this area may participate in the stabilization of otherwise non-substrate compounds.

Case review and quantity of outpatient care.

Case review for patients belonging to a health maintenance organization was implemented in a hospital-based, multidisciplinary, outpatient clinic after the influx of 28,000 Medicaid enrollees. One-year follow-up of 138 patients with prepaid mental health insurance and 283 patients with fee-for-service mental health insurance revealed an annual mean of 6.1 treatment sessions; 78% completed treatment within eight sessions. The modal treatment was a single visit. Prepaid and fee-for-service patients did not differ in amount of care, although significant differences were found for insurance subgroups. These preliminary results suggest that case review has little effect on quantity of care.

Pathophysiologic aspects of human botulism.

Physiologic studies were carried out in six patients with botulism. Abnormalities were those of a defect of acetylcholine release. Although the most consistent findings were small, evoked muscle action potentials (MAP) and posttetanic facilitation similar to the Eaton-Lambert syndrome, there were differences. In botulism as opposed to the Eaton-Lambert syndrome, the following were true: (1) posttetanic facilitation of the amplitude of the evoked MAP was considerably less and did not approach the normal value when the block was severe; (2) posttetanic facilitation persisted at least several minutes during the postactivation cycle; (3) posttetanic depression did not occur; (4) significant tetanic facilitation of the amplitude of the MAP occurred in less than half the patients and, even then, did not approach normal (on the other hand, a decremental response, as in myasthenia gravis, is not seen); and (5) no decremental response of the MAP occurred during slow rates (two per second) of nerve stimulation. Evidence of transient physiologic denervation occurred as in experimental animals affected by botulinum toxin. All physiologic abnormalities revert to normal in association with clinical recovery.

Contraction pseudotremor of chronic denervation.

The tremulousness observed with voluntary muscle contraction in patients with chronic denervating illness has long been described but has been given misleading and confusing labels. The phenomenon is generally attributed to the nonsmooth contraction of a muscle populated by motor units decreased in number and enlarged. Contraction pseudotremor of chronic denervation may be a more appropriate label for this useful clinical sign.

Facial myokymia. Pathological features.

Pathologic examination in a case of facial myokymia showed edema and mild astroglial proliferation of the ipsilateral seventh nerve nucleus; gliomatous tumor involvement occurred rostral to this nucleus. These findings give circumstantial support to functional deafferentation as the cause of facial myokymia.

Pupil-sparing oculomotor nerve palsy due to midbrain infarction.

Vasculopathic oculomotor nerve palsies with pupillary sparing are thought to be due to ischemic damage to the nerve in the subarachnoid space or the cavernous sinus. We present two cases of patients with isolated pupil-sparing oculomotor nerve palsies due to midbrain infarcts. Focal ischemic midbrain lesions should be considered in cases of pupil-sparing oculomotor nerve palsies.

Reversible ipecac myopathy.

The abuse of ipecac syrup for three years resulted in painless, nonfatigable, chiefly proximal weakness in a 27-year-old woman. Electromyography (EMG) and a muscle biopsy revealed features of a myopathy similar to those previously reported in experimental emetine myopathy. Clinical weakness and EMG abnormalities improved after discontinuation of ipecac administration. A direct toxic action of ipecac (acting through its active alkaloid, emetine hydrochloride) on muscle fibers seemed to be responsible for the weakness in this patient.

Chronic human colchicine neuropathy and myopathy.

A 43-year-old woman who indiscriminately took colchicine for five years developed a progressive multisystem syndrome that included severe axonal neuropathy and a pathologically striking myopathy. The neuropathy and myopathy were similar to experimental animal colchicine-induced neuromuscular toxicity.

Inclusion body myositis and chronic immune thrombocytopenia.

We report a case of inclusion body myositis and chronic immune thrombocytopenia with serum platelet antibodies and circulating immune complexes. Although immune mechanisms probably play an important role in the pathogenesis of inclusion body myositis, a viral etiology cannot be excluded.

Stapedius reflex decay in myasthenia gravis.

Stapedius reflex decay, in response to a one-minute sound stimulus of 500 Hz occurred in six patients with myasthenia gravis. This decay is analagous to the decremental response of muscle action potentials to rapid nerve stimulation. Edrophonium chloride decreases the degree of decay. This represents a useful test in the diagnosis of myasthenia gravis.

Nemaline myopathy. Evidence of dipeptidyl peptidase I deficiency.

Fluorescent protease histochemical analysis of muscle biopsy specimens from two patients with nemaline myopathy revealed the apparent absence of one proteolytic enzyme, dipeptidyl peptidase. Although the function of peptidases in normal muscle is obscure, this abnormality suggests that proteases may participate in posttranslational modification of proteins that are to be assembled into Z lines or, alternatively, in the disassembly and degradation of Z-line material.