Usefulness of delayed hypersensitivity skin tests in HIV infected patients

Letters to the Editors 499 Sparfloxacin and clinafloxacin were the most active agents against ciprofloxacin-susceptible E. faecium strains (Table 2). Pefloxacin, however, was the least active agent, yielding an MIC230 value of 16 nig/L. If, again, a breakpoint of 1 mg/L is applied, none of the strains was susceptible to pefloxacin. Norfloxacin and ofloxacin also showed very low activity against these strains. For ciprofloxacin-resistant E. faecium strains. all the quinolones showed MIC5o values lower than those observed against ciprofloxacin-resistant E.faecu1is strains. In terms of MIC90 clinafloxacin was again the most active fluoroquinolone against ciprofloxacin-resistant E.jhecium strains, 42% and 51% of these strains were inhibited by 1 mg/L of sparfloxacin and clinafloxacin, respectively. The high in vitro activity of clinafloxacin against enterococci has been described [6,7]. Nevertheless, the MICso values obtained in this study are greater than those obtained in previous studies, suggesting a slow decrease in the susceptibility of enterococci to this agent. The other new quinolones, levofloxacin, sparfloxacin and trovafloxacin, did not improve on the results obtained with clinafloxacin. In summary, clinafloxacin, and to a lesser extent sparfloxacin, levofloxacin and trovafloxacin, showed greater in vitro activity than the classical fluoroquinolones against enterococci. Taking into account the few therapeutic alternatives for infections caused by rnultiresistant strains, further experimental studies will be needed to determine if these new fluoroquinolones will be useful in the treatment of serious enterococcal infections caused by strains resistant to other antibiotics. Acknowledgments This work was partially supported by a grant (PB941424) from the Direcci6n General de Investigacion Cientifica y Tkcnica (DGICYT), Spain. The authors thank P. Hidalgo and J. Dawson for the preparation of the manuscript. Luis Mavtinez-ll.~arti~~ez', Providencia Joyanes ', Alvuro Pascual', Eurique Terrero I, Evelio J Perea' 'Department of Microbiology, University Hospital V. Macarena, School of Medicine, Seville, Spain; 'Department of Microbiology, School of Medicine, Apdo 914, 41080-Seville, Spain References 1. Ernori TG, Gaynes RP. An overview of nosocomial infections, including the role of the microbiology laboratory Clin Microb Rev 1993; 6: 428-42. 2. Gordon S, Swenson JM, Hill BC, et al. Antimicrobial susceptibility patterns of comnion and unusual species of enterococci cauting infections iii the United States. J Clin Microbiol 2992; 30: 2373-8. Barry AI, Fuchs PC. Cross-resistance and crosg-tusceptibility between fluoroquinolone agents. EurJ Clin Microbiol Infect Dis 1991; 10: 1013-18. Facklam RR, Sahm DE Enterococcus. In Murray PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH, eds. Manual of clinical microbiology, 6th edn. Washington, LIC: American Society for Microbiology, 1995: 308-1 4. National Committee for Clinical Laboratory Standudt. Methods for dilution antimicrobial susceptibility test for bacteria that grow aerobically, 3rd edn. Approved Standard. NCCLS document M7-A3. Villanova, PA: National Committee for Clinical Laboratory Standards, 1993. Burney S, Landman U, Quale JM. Activity of clinafloxacin against multidrug-reqistant Entcrococcus $eciimi. Antimicrob Agents Cheniother 1994; 38: 1668-70. I'iddock LJV New quinoloiies and Gram-pos1tive bacteria. Antimicrob Agents Chemother 1994; 38: 163-9. Usefulness of delayed hypersensitivity skin tests in HIV infected patients Clin Microbiol Infecf 1997; 3: 499-500 The demands on the health services by patients infected with type 1 human immunodeficiency virus (HIV-1) are increasing markedly. In Spain, past or present intravenous drug users account for a significant proportion of the total infected individuals [I]. Their visits to doctors are random and do not fit into defined patterns. In this context, it is extremely important to obtain objective data which may help in the evaluation of their serologic, diagnostic and clinical status. Delayed hypersensitivity skin tests provide a very important diagnostic tool for assessing cellular immunity and several authors have advocated their use in clinical practice at the initial evaluation [2,3]. At the same time, lymphocyte CD4 counts have become widely accepted as an indicator when assigning a prophylactic or therapeutic regimen and in establishing life-expectancy [4,5]. This indicator has gained universal currency with the publication of the latest CDC criteria for staging and clinical categorization [6]. The objective of the present work is to evaluate the response to a skin test consisting of five bacterial and two fungal antigens (Ag) in a sample of HIV-1 infected individuals at their first visit to the doctor and to establish its relation to the CD4 lymphocyte count. Between October 1985 and March 1993 we studied a total of 503 individuals with risk factors who presented for clinical evaluation at the University Clinical Hospital of Valladolid. Their average age was 29 k 7 years (range: 500 Clinical Microbiology and Infection, Volume 3 Number 4, August 1997 16-74) and 72% were males. Ninety-two per cent of these subjects had a history of past or present intravenous drug use. A cutaneous skin test was performed in all the patients at the beginning of the study with Multitest IMC (Institut MCrieux, Lyon), which includes Clostridiurn tetani, Covynebactevium diphtheriae, Streptococcus group C, Mycobacterium tuberculosis, Proteus mirabilis, Candida albicans and Tvichophyton mentagrophytes, and it was read 48-72 h later. We also obtained an absolute CD4 lymphocyte count on peripheral blood. The Multitest response was classified as ‘normal’ when there was frank response to more than two antigens, ‘partial’ if there was response to one or two antigens, and ‘anergic’ when no reactivity or reactivity below control level (glycerin) was found. The chisquared statistical test was used for making comparisons. Table 1 Relationship between cutaneous Multitest and CD4 lymphocyte count CD4 lymphocytes/mn3 Response to cutaneous Multitest No. <200 2200 is twofold. First, these patients are infrequent clinic attenders and also have difficult venous access; skin testing may partly help to overcome this difficulty. Second, there is a11 increasing problem of tuberculosis in these patients; multiple skin tests are helpful in assessing the value of Mantoux testing. One important difficulty remains: ensuring that the reading of the skin tests is homogeneous. Ideally, we should determine the inter-observer variation (K-COefflCient); more studies are necessary in order to control the information bias derived from the interpretation carried out by several observers. Jose Ma Eiros, Prudencio Martinez, Rad Ortiz de Lejarazu, Antonio Orduiia, Luis Inglada, Antonio Roddguez-Torres2 ‘Microbiologia, Facultad de Medicina, Avda Rambn y Cajal, 7, 47005 Valladolid, Spain; 2Facultad de Medicina y Hospital Clinic0 Universitario, Valladolid, Spain NormaVPartial 329 20 309 Anergic 174 21 153 Total SO3 41 462 Abnormal or partial responses to Multitest IMC were seen in 329 patients and 174 were anergic. Table 1 shows these data categorized according to the total CD4 lymphocyte count. We found that in anergic patients the relative risk of having a CD4 count <200/mm3 was 1.985 (95% CI: 1.107-3.561, p<0.02). There was no significant difference in terms of CD4 count between normal and partial responders. We chose this ‘cut-off according to CD4 cell category (subgroup 3) in the CDC classification. This important association (delayed hypersensitivity testing with CD4) should be clinically useful in HIV+ intravenous drug users, particularly in developing countries which do not have easy access to CD4 count monitoring. It seems clear that viral load is the most useful marker of disease progression. Our data are in line with those often found in clinical studies [3,7] and support the utilization of rapid tests in clinical practice. In our experience the cutaneous Multitest is a valuable alternative in the context of initial clinical evaluation, offering a good correlation with CD4 circulating levels, because of its low cost and easy application. In our practice with a large proportion of intravenous drug users who are HIV infected, the practical importance of delayed hypersensitivity testing References 1. Registro Nacional de Casos de Sida. Vigilancia Epidemio16gica de SIDA en Espafia a fecha de actualizaci6n 31 de diciembre de 1995. Pub Of Seisida 1996; 7: 325-35. 2. Caiaffa WT, Ghaham NM, Galai N, RIZZO RT, Nelson KE, Vlahov D. Instability of delayed-type hypersensitivity skin test anergy in human immunodeficiency virus infection. Arch Intern Med 1995; 155: 2111-17. 3. Dolan MJ, Clerici M, Blatt SP, et al. In vivo T cell function, delayed-type hypersensitivity shn testing, and CD4+ T cell subset phenotyping independently predict survival time in patients infected with human immunodeficiency virus. J Infect Dis 1995; 172: 79-87. 4. Saravolatz L, Neaton JD, Sacks L, Deyton L, Rhame F, Sherer R for the Terry Beirn Community Programs for Clinical Research on AIDS. CD4+ T lyniphocyte counts and patterns of mortality among patients infected with human immunodeficiency virus who were enrolled in community programs for clinical research on AIDS. Clin Infect Dis 1996; 22: 5. Stein DS, Korvick JA, Vermund SH. CD4+ lymphocyte cell enumeration for prediction of clinical course of human immunodeficiency virus disease: a review. J Infect Dis 1992; 6. CDC 1993. Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 1992; 41: 1-19. 7. Huebner RE, Schein MF, Hall CA, Barnes SA. Delayed-type hypersensitivity anergy in human immunodeficiency virusinfected persons screened for infection with Mycobarterium tuberculorb. Clin Infect Dis 1994; 19: 26-32. 513-20. 165: 352-63.