C. H. Collins

Vancomycin-resistant enterococci

In a previous commentary, we made the case that the fear of methicillin resistant Stnpl~yZc~occus QZLY~US (MRSA) in their burn units caused some clinicians to use vancomycin, inappropriately, as a first line antibiotic to treat patients with clinical signs of sepsis in the absence of microbiological evidence that the patient was, indeed, infected with MRSA [l]. Our concern was that vancomycin resistance information could be transferred MRSA from vancomycin resistant enterococci (VRE), which are becoming more prevalent in acute care treatment facilities, and that inappropriate use of this antibiotic would select for a vancomycin resistant MRSA. This bacterium, now resistant to vancomycin, the only antibiotic to which it was uniformly susceptible, heretofore, would be a ‘superbug’ causing infections exceedingly difficult to treat. We believe that inappropriate use of vancomycin in burn units because of inordinate fear of MRSA hastens the scenario described above. Therefore, lwe underscored the use of some well accepted guidelines [2,3], for vancomycin use in the treatment of burn infections. Another aspect of the inappropriate use of vancomycin, however, was not addressed previously: the generation and selection of VRE, per se. Enterococci associated with cultures obtained from burn patients have been on the increase, worldwide, over the past decade. In 1990, enterococci were the most prevalent bacterial isolate in a Swiss burn unit [4] and the third most prevalent isolate in a Norwegian burn center [5]. A report from an Italian burn unit which surveyed infections between the years 1976 and 1988 stated ‘The most striking finding was the increase in antibiotic resistant enterococci.’ [6] In the US, one burn center reported an increase in isolation of enterococci from 5 per cent in 1984 to 19 per cent in 1988 [7], and another unit reported that in a 3-year study period (1989-91), enterococci were responsible for 11-13 per cent of all infections in their patients [8]. Concomitant to their increased associations with burned patients, enterococcal infections rose in the general hospital environment and are now among the four most common nosocomial pathogens in the US and have been called the ‘nosocomial pathogens of the 1990s’ [9]. While there are a number of species in the genus Enterococcus, two species, E. faecalis and E. faecdium are associated with the largest numbers of nosocomial infections with the other species playing more minor roles [lo-131. Three types of antimicrobial resistance are associated with enterococci [lo]: Intrinsic this is defined as intrinsic resistance to several classes of antimicrobials that are normally active against (other types of streptococci (low level aminoglycosides, azthreonam, cephalosporins, clindamycin, imipenem [JZ. faecium], penicillin, trimethoprim-sulfamethoxazole). Tolerance (cell-wall active agents) where the minimal bactericidal concentration of antibiotic is far in excess of the minimum inhibitory concentration. Thus, concentrations of cell-wall active agents which will inhibit the growth of enterococci will not kill them. This becomes of considerable significance in infections, such as, endocarditis, osteomyelitis and memngitis, where bactericidal activity of antibiotics are essential for achieving acceptable cure rates [9]; Acquired the past two decades have seen the acquisition of resistance determinants to virtually every act.& antimicrobial agent [lo], including vancomycin [10,13-151, the ‘last, best hope’ for the treatment 0: enterococcal infections, and the subject of this commentary. Three phenotypes of VRE. Van A, Van B and Van C have been known for sometime [13] with a fourth phenotype, Van D, having been described recently [16j (Table 1). The various phenotypes are associated more or less with specific species of enterococci and these phenotypes vary in their susceptibility to another glycopeptide antibiotic, teicoplanin: Van A and Van B phenotypes exhibit clinically relevant inducible levels of vancomycin resistance, plus resistance to multiple other antibiotics. Their resistances are genetically transferable and they occur in enterococcal species most commonly involved in serious infections. They can be distinguished from each other by the fact that Van A strains are resistant to teicoplanin as well as vancornycin, while Van B strains are not. While not a !ot is

Subdivision of Mycobacterium tuberculosis into five variants for epidemiological purposes: methods and nomenclature.

Virulent strains of Mycobacterium tuberculosis isolated from humans are divisible into five variants by using four tests: oxygen requirement (aerobic or microaerophilic), nitrate reductase activity, susceptibility to pyrazinamide (60 micrograms/ml) and susceptibility to thiophene-2-carboxylic acid hydrazide (5 micrograms/ml). The five variants are referred to as Classical human, Asian human, bovine, African I and African II. The relation of these variants to previously described types is discussed. This simple division has been shown to be useful in epidemiological studies.

Bacteriological survey of tuberculous lymphadenitis in South-east England: 1973-80.

During the eight years 1973-80 the Public Health Laboratory Service Regional Centre for Tuberculosis Bacteriology received cultures of mycobacteria from 2339 patients with tuberculous lymphadenitis. Of these, 2272 were M tuberculosis (2207 human and 65 bovine strains) and 67 were other mycobacterial species, usually M avium and its intracellulare variant. Disease due to the human strains of M tuberculosis occurred most often in young women of Asian ethnic origin. Many bovine strains isolated from Asian patients differ from the classical bovine type in being sensitive to pyrazinamide: the origin of these strains, whether from other people or from cattle, is unknown. Lymphadenitis due to bovine strains tended to occur in an older age group than the human strains and probably include relatively more cases of reactivation diseases. Infection caused by the other mycobacterial species occurred mainly in young children of European origin. Tuberculosis, therefore, remains an important cause of lymphadenopathy in Britain.

In vitro activity of ciprofloxacin in combination with standard antituberculous drugs against mycobacterium tuberculosis

Chequer-board titrations show that the in vitro activity of ciprofloxacin against Mycobacterium tuberculosis is independent of that of streptomycin, isoniazid, ethambutol and pyrazinamide and confirm that there is antagonism between ciprofloxacin and rifampicin.

Names for mycobacteria.

To the founding fathers of bacteriology the nomenclature of pathogens was straightforward. Tuberculosis was caused by the tubercle bacillus and leprosy was caused by the leprosy bacillus and when these pathogens were allocated to the genus Mycobacterium this posed no problem, they merely became M tuberculosis and M leprae. This golden age of simplicity in nomenclature was, however, short lived as it soon became apparent that tubercle bacilli were not all identical and that

Differentiation of bcg from other variants of Mycobacterium tuberculosis isolated from clinical material

BCG isolated from clinical material may be reliably differentiated from other variants within the species Mycobacterium tuberculosis by means of a few simple cultural and biochemical tests and by bacteriophage typing. Animal pathogenicity tests may therefore be avoided.

Sensitivity of opportunist mycobacteria to rifampicin and ethambutol

A total of 1237 strains of opportunist mycobacteria were tested for sensitivity to rifampicin and ethambutol. Most strains of Mycobacterium kansasii and all strains of M. marinum tested were sensitive to both drugs. A variable pattern was given by M. xenopi strains, but a general resistance was observed with the M. avium--intracellulare--scrofulaceum group. All strains of M. fortuitum and M. chelonei were highly resistant. Scotochromogens were mostly sensitive to ethambutol, but there was variable resistance to rifampicin. These properties may be useful in identification of species. No acquired resistance was found in follow-up cultures from confirmed cases of mycobacterioses, but details of therapy, if any, were not known.

Differentiation of Mycobacterium chelonei from M. fortuitum by ciprofloxacin susceptibility.

Seventy-five strains of Mycobacterium fortuitum were inhibited by 3.0 mg/l ciprofloxacin but 36 strains of M. chelonei were resistant. The results correlated well with those obtained by the nitratase test. The ciprofloxacin sensitivity test is a useful supplement to the tests used to identify these two species.

Hydroxylamine sensitivity and salt tolerance in screening and identifying mycobacteria

Hydroxylamine sensitivity offered no advantage over p-nitrobenzoic acid in distinguishing between tubercle bacilli and other (opportunist and non-significant) mycobacteria. It was of limited use in identification procedures. Salt tolerance assisted in the identification of strains which may be Mycobacterium triviale and M. chelonei var borstelense.

Tuberculosis and the cow

The debate about the transmission of tuberculosis from badgers to cattle, which commenced in the early 1970s, has overshadowed the study of human tuberculosis due to the bovine tubercle bacillus, the two-way transmission of the disease between humans and bovines and the role of the former as a reservoir of the disease. The causative organism of tuberculosis, variously known as consumption and phthisis, defied identification until 1882 when Robert Koch published his milestone paper ’Die Aetiologie der Tuberkulose’ in which he described its isolation from both human and bovine material. He did not give it a scientific name but simply referred to it as the ’Tuberkelbazillus’. It was named Bacillus tuberculosis by Zopf ( 188 3 ) and was given its currently valid title Mycobacterium tuberculosis by Lehmann and Neumann (1896). The generic name, meaning fungusbacterium, is an allusion to its fungus-like growth on liquid media. A few years later, an American, Theobald Smith, observed certain morphological and cultural differences between tubercle bacilli isolated from humans and cattle. He referred to these as the ’human’ and ’bovine’ varieties although he warned against the assumption that they were restricted to the hosts after which he named them (Smith, 1898). These varietal names remained in common use for over 70 years, until Karlson and Lessel (1970) proposed the taxon Mycobacterium bovis, which was included in the ’Approved Lists of Bacterial Names’ (Skerman et al, 1980). Some bacteriologists doubt the validity of this separate species and also of another tubercle bacillus, M africanum (Castets et al, 1969), considering them to be variants of M tuberculosis. Although recent studies on genomic relatedness support this view, the separate species names remain in use but they are often grouped together under the unsatisfactory term M tuberculosis complex. Soon after the discovery of the human and bovine tubercle bacilli, ’avian tubercle bacilli’ were isolated from birds and ’coldblooded tubercle bacilli’ from reptiles and amphibians. These terms are obsolete as the organisms now bear specific names. These bacilli, in common with many other mycobacterial species, are essentially environmental saprophytes whereas s