Clinical significance of donor-unrecognized bacteremia in the outcome of solid-organ transplant recipients.

We evaluated the clinical significance of unrecognized bacteremia in the organ donor (i.e., blood culture results that were reported to be positive after transplantation) on the outcome of transplant recipients. Twenty-nine of 569 liver and heart donors (5%) had bacteremia at the time of organ procurement, but there were no documented instances of transmission of the isolated bacteria from the donor to the recipient. Unrecognized bacteremia in the donor does not have a negative clinical impact on the outcome of organ transplant recipients.

Absence of maternal-fetal transmission of human immunodeficiency virus type 1 to second-trimester fetuses.

OBJECTIVE: The aim of this study was to evaluate the contribution of in utero infection to the vertical transmission of human immunodeficiency virus type 1 during the second trimester. STUDY DESIGN: We examined fetal tissues from 21 second-trimester prostaglandin-induced abortions among human immunodeficiency virus type 1-infected women and compared the fetal vertical transmission rates with those among children born to human immunodeficiency virus-seropositive women. The presence of human immunodeficiency virus type 1 nucleic acid sequences was investigated with two different highly sensitive polymerase chain reaction techniques in tissue samples from the fetal thymus, lung, and brain. RESULTS: No human immunodeficiency virus type 1 deoxyribonucleic acid was detected in any of the samples. CONCLUSION: The absence of human immunodeficiency virus type 1 in all fetuses in our study is compatible with a low rate of maternal-fetal transmission during the second trimester of pregnancy.

Prevalence and risk factors of tinea unguium and tinea pedis in the general population in Spain.

This study prospectively evaluated the prevalence and risk factors of tinea unguium and tinea pedis in the general adult population in Madrid, Spain. One thousand subjects were clinically examined, and samples of nails and scales from the interdigital spaces of the feet were taken from those patients presenting with signs or symptoms of onychomycosis and/or tinea pedis, respectively. In addition, a sample from the fourth interdigital space of both feet was collected from all individuals with a piece of sterilized wool carpet. Tinea unguium was defined as a positive direct examination with potassium hydroxide and culture of the etiological agent from subjects with clinically abnormal nails. Patients with positive dermatophyte cultures of foot specimens were considered to have tinea pedis. The prevalence of tinea unguium was 2.8% (4.0% for men and 1.7% for women), and the prevalence of tinea pedis was 2.9% (4.2% for men and 1.7% for women). The etiological agents of tinea unguium were identified as Trichopyton rubrum (82.1%), followed by Trichopyton mentagrophytes var. interdigitale (14.3%) and Trichopyton tonsurans (3.5%). Trichophyton rubrum (44.8%) and Trichophyton mentagrophytes (44.8%), followed by Epidermophyton floccosum (7%) and T. tonsurans (3.4%), were the organisms isolated from patients with tinea pedis. The percentage of subjects who suffered simultaneously from both diseases was 1.1% (1.7% for men and 0.6% for women). In a multivariate logistic regression analysis, age (relative risk [RR], 1.03) and gender (RR, 2.50) were independent risk factors for tinea unguium, while only gender (RR, 2.65) was predictive for the occurrence of tinea pedis. In both analyses, the presence of one of the two conditions was associated with a higher risk for the appearance of the other disease (RR, >25).

rpoB mutations as an epidemiologic marker in rifampin-resistant Mycobacterium tuberculosis.

SETTING: Cases of rifampin-resistant Mycobacterium tuberculosis from the prison population in Madrid and from the general population in Spain. OBJECTIVE: To identify the rpoB mutations associated with resistance to rifampin and to investigate rpoB genotyping as an epidemiological marker in rifampin-resistant M. tuberculosis. DESIGN: Twenty-nine rifampin-resistant clinical isolates of M. tuberculosis, 15 obtained from the prison population in Madrid and 14 from the general population in Spain, were characterized by sequence analysis of the 81-bp core region of the rpoB gene and IS6110 DNA fingerprinting. RESULTS: All the isolates had mutations in rpoB, with those in codon 531 accounting for 41% of the total. Twenty-three (79%) isolates were highly resistant to rifampin (minimum inhibitory concentration > or = 64 mg/L). Nineteen different IS6110 fingerprints were observed: one was shared by seven isolates, one by three, two by two, and 15 were unique. Two IS6110 clusters could be divided into subclusters on the basis of rpoB analysis. Epidemiologic links were identified among patients whose isolates had identical IS6110 patterns and rpoB genotypes, but not between those with identical IS6110 patterns and different rpoB genotypes. CONCLUSION: Characterization of rpoB mutations can provide information about susceptibility to rifampin and be a useful epidemiological tool for discrimination of rifampin-resistant strains of M. tuberculosis with identical IS6110 fingerprints.

Heterosexual transmission of HIV-1 is associated with high plasma viral load levels and a positive viral isolation in the infected partner.

Risk factors for heterosexual HIV transmission are not fully understood. In fact, a proportion of people with sexual exposure to HIV remain uninfected despite multiple and continuous intercourse with HIV-infected partners. In this work, we have analyzed those virologic parameters potentially involved in the transmission of HIV through heterosexual contact. Thirty-eight couples with continuous unprotected sexual intercourse were included. HIV transmission occurred in 10 of 38 couples. No differences in clinical characteristics, exposure time, sexual practices, CD4 counts, or polymorphism in CCR5 were found between transmitter and nontransmitter groups. In contrast, virologic data were different between both groups; median values of viral load were 21.139 and 5.484 RNA copies/ml of plasma in the transmitter and nontransmitter groups, respectively, and a significant difference was found in mean viral load values (p = .03, Mann-Whitney test). Viral isolation was obtained in 90% of transmitters, but in only 44% of nontransmitter subjects (p = .02, Fisher's exact test). These data show that viral load levels and a positive viral isolation in culture must be considered as risk factors for heterosexual transmission of HIV-1.

Evidence of exogenous reinfection and mixed infection with more than one strain of Mycobacterium tuberculosis among Spanish HIV-infected inmates.

BACKGROUND: As prisons have a high prevalence of tuberculosis and HIV infection, we studied the possibility of multiple tuberculosis infections in a selected population of HIV-infected inmates. METHODS: Two groups of patients with special characteristics were selected from 226 HIV-infected inmates diagnosed with tuberculosis in the prisons of Madrid (Spain) between 1993 and 1994. The first group contained nine patients who remained culture positive 4 months after the initiation of therapy and the second group contained 28 patients with Mycobacterium tuberculosis isolated from different anatomical sites. DNA typing with IS6110 was performed on all isolates from these patients. In some patients a secondary DNA typing with the plasmid pTBN12 was performed. RESULTS: Two patients from group A had a second M. tuberculosis strain obtained 4 and 18 months after the initial isolate, with different IS6110 and pTBN12 patterns. In one patient the second strain was multidrug resistant and in the other patient both strains had the same drug-susceptible pattern. The clinical and microbiologic evidence in both patients was consistent with the presence of active tuberculosis caused by a new strain of M. tuberculosis. In group B, the isolates from 27 patients shared similar fingerprint pattern; however, in one patient isolates from sputum and urine showed different IS6110 and pTBN12 patterns, although both strains showed the same drug-susceptible phenotype. CONCLUSION: This study provides evidence that HIV-infected inmates living under conditions of high environmental infectivity can be infected with two different strains of M. tuberculosis. This finding has implications for the tuberculosis-control programs in prison.

Prevalence of undetected tinea capitis in a prospective school survey in Madrid: emergence of new causative fungi.

From October 1994 to December 1996, a prospective study was undertaken in 10,000 unselected school children in Madrid, aged between 2 and 16 years (mean +/- SD 8.5 +/- 3.6 years). Fifty-two (0.52%) (including 13 immigrants from Africa) had dermatophytes in the scalp: 33 (0.33%) (including 10 immigrants from Africa) had tinea capitis and 19 were scalp carriers. Almost half of the symptomatic cases were caused by Trichophyton tonsurans (12 of 33 cases) and Microsporum canis (16 of 33 cases). T. tonsurans (13 of 19 cases) was the predominant species in the scalp carriers. Twenty-four per cent of the subjects with tinea capitis and 42% of the asymptomatic scalp carriers also had ringworm in other body sites. There was a significantly higher occurrence of tinea capitis (P < 0.001) (particularly due to T. tonsurans: P < 0.001) and of asymptomatic scalp carriers (P < 0.05) (particularly due to anthropophilic species: P < 0.01) in the immigrant population from Africa.

In vitro selective elimination of HIV-infected cells from peripheral blood in AIDS patients by the immunotoxin DAB389CD4.

OBJECTIVES: To study the antiviral efficacy of the recombinant immunotoxin DAB389CD4 against wild-type strains of HIV and to analyse its potential toxicity in non-infected peripheral blood mononuclear cells (PBMC). DESIGN AND METHODS: PBMC from HIV-seropositive patients were cultured in the presence of DAB389CD4. After 30 days in culture, viral load was assessed by quantification of RNA levels in supernatants and HIV-specific polymerase chain reaction (PCR) was performed for measuring proviral DNA as an indicator of remaining virus in cells. To study the toxicity of DAB389CD4, PBMC from healthy donors were isolated and cell viability and lymphocyte proliferation were assessed after immunotoxin treatment. RESULTS: DAB389CD4 presented a strong antiviral activity in five of the six primary isolates decreasing p24 production in cultures to undetectable levels and eliminating selectively HIV-infected cells as measured by HIV DNA-specific PCR. One viral isolate was resistant to DAB389CD4 treatment. The immunotoxin was active against both syncytial and non-syncytial HIV strains. DAB389CD4 was not toxic in non-infected PBMC as measured by different techniques: trypan blue exclusion, methyl thiazol tetrazolium oxidation, lymphocyte proliferation, and CD4 cell count. CONCLUSIONS: DAB389CD4 showed a strong antiviral and specific activity against primary HIV isolates by killing selectively HIV-infected cells without affecting non-infected cells. This antiviral effect produced the eradication of HIV in cultures and indicated the potential use of this drug as a new therapeutic tool in combination with antiretroviral drugs. This immunotoxin would be especially interesting in the context of the marginal populations of HIV-infected cells remaining after successful antiviral treatment.

Clinical, virological, and histologic evolution of hepatitis C virus infection in liver transplant recipients.

We designed a prospective study to assess the time course and evolution of hepatitis C virus (HCV) infection in 152 patients who underwent a liver transplantation (LT) in our institution. Forty-four recipients (29%) were infected by HCV after transplantation: 40 who developed recurrent infection after LT and four who acquired infection during or after LT. No differences were found in survival actuarial rates at 1, 2, and 4 years after transplantation for patients infected by HCV vs. noninfected ones. Graft hepatitis occurred in 66% of HCV-infected recipients: 18 developed chronic active hepatitis (10 of them with intense fibrosis) and 2 developed cirrhosis during the follow-up. Infection by the HCV-1b genotype was found in 79% of the infected recipients and in 100% of those in whom histologic evolution was worst. Fourteen grafts were lost in 44 HCV-infected recipients, in comparison with 12 in 108 HCV-negative patients (P = .007), mostly because of chronic rejection. HCV infection did not affect life expectancy in the midterm follow-up for LT patients. However, it was often associated with the occurrence of early and severe graft hepatitis and with a higher incidence of graft loss due to chronic rejection.

[Tolerance and safety of carbapenems: the use of meropenem]. / Tolerancia y seguridad de los carbapenémicos: el uso de meropenem.

The purpose of this article is to review the safety and tolerance of two carbapenems (imipenem/cilastatin and meropenem) in order to establish their possible use in different clinical settings. The tolerance and safety profile of both carbapemens in intravenous and intramuscular formulation is good. With imipenem/cilastatin, nausea and vomiting can constitute a practical problem requiring prolonged times of perfusion and high dilutions. The possibility of administering meropenem in intravenous infusion or bolus injection with lower volumes of fluid, without increasing the incidence of these adverse reactions, may have practical advantages in special situations. The possible neurotoxicity of the imipenem/cilastatin presents limitations of the use in high risk circumstances such as meningitis, previous alterations of CNS, renal insufficiency and concomitant administration of other drugs with neurotoxic profiles and when high doses of administration are needed. The meropenem, by the contrary, can be used in patients with infections of the CNS and other risk factors, at high doses, without increased risk of seizures.

Prevalence of undetected tinea capitis in a school survey in Spain.

From October 1994 to November 1995, a prospective study aiming to detect dermatophytes on the scalp was undertaken in 5000 unselected school children aged between 3 and 16 years (mean age 8.34 years, SD +/- 3.83). Thirty-two (0.64%) had dermatophytes in the scalp, 22. (0.44%) had tinea capitis and 10 were asymptomatic scalp carriers. It is important to point out that 33% of the patients with tinea capitis and 60% of the asymptomatic scalp carriers also had ringworm in other body sites. There was a significantly higher proportion of cases of tinea capitis (P < 0.001)(particularly due to Trichophyton tonsurans, P < 0.001) and of cases of asymptomatic scalp carriers (P < 0.05) (particularly due to Trichophyton tonsurans, P < 0.001) in the immigrant population of African origin. In all the child index cases with positive scalp cultures (tinea capitis and carriers), the household members were studied clinically and mycologically. One child had a body ringworm caused by Microsporum canis. Twelve adults had positive cultures with dermatophytosis (one tinea capitis and eleven body ringworm). Three adult patients were also carriers of dermatophytes in other body sites. Our data indicate a change in the causative agents of tinea capitis seen in Madrid over a 12-month period, with cases due to antropophilic species (T. tonsurans, T. soudanense, M. audouinii and T. violaceum) occurring in the immigrant population from Africa; as a consequence, there is an emergence of T. tonsurans in the Spanish population.

Randomized trial of fluconazole versus nystatin for the prophylaxis of Candida infection following liver transplantation.

A prospective, randomized, multicenter study addressed the safety and efficacy of fluconazole therapy in 143 liver transplant patients. Seventy-six patients received daily oral fluconazole (100 mg), and 67 received nystatin (4 X 10(6) U) during the first 28 days after transplantation. Candida colonization occurred in 25% and 53% of patients in the fluconazole and nystatin groups, respectively (P = .04), and 13% and 34% of patients in the respective groups had Candida infections (P = .022). Of these patients, 10.5% in the fluconazole group and 25.3% in the nystatin group had superficial candidal infections (P = .024). Invasive candidiasis developed in 2 patients in the fluconazole group (2.6%) and 6 in the nystatin group (9.0%) (P = .12). There was no increased hepatotoxicity, cyclosporine interaction, or emergence of clinically relevant resistant Candida strains attributable to fluconazole. Thus, oral fluconazole (100 mg) is safe and reduces Candida colonization and infection after liver transplantation.

[Use of DNA sequence hybridization with specific oligonucleotide probes to identify hepatitis C virus genotypes]. / Utilización de la hibridación de secuencias de DNA con sondas específicas de oligonucleótidos para identificar genotipos del virus de la hepatitis C.

BACKGROUND: Recent development of an assay based on the hybridization of the amplification product obtained by polymerase chain reaction (PCR) of the RNA of hepatitis C virus (HCV) with specific probes for each viral genotype ("reverse-hybridization"), has permitted to have a rapid, simple and reproductible technique to identify the different genotypes of HCV. The identification of HCV genotypes seems to be important given their different pathogenic capacity and response to interferon therapy. METHODS: We prospectively studied 221 patients with HCV infection defined by the detection of viral RNA in serum by "nested-PCR". HCV genotype was determined by "reverse-hybridization" using specific oligonucleotide-probes for each genotype corresponding to the 5, UTR. RESULTS: HCV 1b genotype was predominant in 221 patients studied (180/221, 81%), followed by 1a (10%) and by 3 and 4 (4% respectively). Two patients presented mixed infection (1a/1b). No case of infection by genotypes 2 and 5 was found. The predominance of 1b genotype was more evident in adults than in children (83 vs 62%) (p < 0.05). CONCLUSIONS: HCV 1b is the predominant genotype among our patients with hepatic disease induced by HCV. The reverse-hybridization assay is a simple and rapid technique that permit the identification of the most important genotypes of hepatitis C virus.

Detection of vertical transmission of human immunodeficiency virus type 1 by a commercial polymerase chain reaction assay.

In a prospective study, a commercial polymerase chain reaction (PCR) system was compared with a conventional procedure, based on PCR and hybridization with a radio-labeled probe, for the detection of human immunodeficiency virus (HIV) infection in 131 blood samples from 80 children born to HIV-seropositive mothers. Twenty-three of these children were HIV infected. The sensitivity and specificity of the commercial assay as compared with the conventional PCR procedure were 100% and 95.1%, respectively. This commercial method simplifies the performance of the conventional PCR technique and can be used to detect HIV type 1 vertical transmission.

[Infection of sternal wound in heart surgery: analysis of 1000 operations]. / Infección de la herida esternal en la cirugía cardíaca: análisis de 1.000 intervenciones.

BACKGROUND: Sternal wound infection (SWI) is the most important complication in cardiac surgery. The aim of this study was to describe the frequency and clinical and microbiological features of this complication. METHODS: All the cases of SWI which were observed in the authors' hospital in the first 1,000 cardiac surgery operations performed with extracorporeal circulation were retrospectively reviewed. The cases were identified through the Infectious Diseases and Cardiac Surgery Department files and were classified according to the depth of the infection. During the study period neither the prophylaxis against infection nor the surgical techniques were modified. RESULTS: Forty-three patients (4.3%) presented SWI. Fourteen were superficial infections and 29 were deep infections of which 9 were classified as osteomyelitis and 20 as mediastinitis. A progressive decrease was observed in the proportion of SWI over time parallel to an increase in the number of operations performed. Staphylococcus aureus was the agent most frequently isolated (60.4%). Gram-positive aerobic cocci were found in 66.7% of the total number of isolations, being most frequent in the deep infections (83.3% of the isolations). The gram-negative aerobic bacilli were isolated more frequently in the superficial infections than in the deep infections (57.8% v.s. 16.7% of the isolations, respectively p < 0.01). In patients with SWI the predictive value of the positive blood cultures for the diagnosis of mediastinitis was 83.3%, with a sensitivity of 50% and specificity of 91.3%. Three patients with deep infection developed chronic complications and another three died (mortality by mediastinitis 15.0%). The mean postoperative stay was 52 days for the patients with deep infection and 39 days for those with superficial infection (p = NS). CONCLUSIONS: The percentage of surgical wound infection during the study period showed a trend to a decrease parallel with an increase in the number of operations. The gram-positive bacteria were responsible for most of the SWI. Although the depth of SWI is difficult to clinically predict, the presence of bacteremia suggests the existence of mediastinitis. Despite their lesser clinical importance, the superficial infections carry a long postoperative stay.

Rapid diagnosis of Mycobacterium tuberculosis bacteremia by PCR.

A method based on DNA amplification and hybridization has been used for the rapid detection of Mycobacterium tuberculosis in blood samples from 38 hospitalized patients (15 human immunodeficiency virus [HIV] positive and 23 HIV negative) in whom localized or disseminated forms of tuberculosis were suspected. In 32 of these patients, the diagnosis of tuberculosis was eventually confirmed by conventional bacteriological or histological procedures. M. tuberculosis DNA was detected with the PCR technique in the peripheral blood mononuclear cells from 9 of 11 (82%) HIV-infected patients and in 7 of 21 (33%) HIV-negative patients (P < 0.01), while M. tuberculosis blood cultures were positive in 1 of 8 (12.5%) and 1 of 18 (5.5%) patients, respectively. PCR was positive in all cases with disseminated disease in both HIV-negative and HIV-positive patients and also in the HIV-positive patients with extrapulmonary tuberculosis. Seven samples from patients with documented illness other than tuberculosis and 12 specimens from healthy volunteers, including seven volunteers with a recent positive purified protein derivative test, were used as controls and had a negative PCR. These results suggest that detection of M. tuberculosis DNA in peripheral blood mononuclear cells may be a useful tool for rapid diagnosis of disseminated and extrapulmonary forms of tuberculosis, especially in an HIV-positive population.

Influence of external factors in resistance of Corynebacterium urealyticum to antimicrobial agents.

Corynebacterium urealyticum is usually resistant to multiple antibiotics. We analyzed whether previous hospitalization and/or the use of antibiotics was a factor associated with the appearance of resistance to different antibiotics in C. urealyticum. Our findings suggest that resistant strains of C. urealyticum are likely to be acquired directly from the hospital environment and that the use of antibiotics in the hospital setting could favor the appearance of multiresistant strains.

Prospective randomized trial of efficacy of ganciclovir versus that of anti-cytomegalovirus (CMV) immunoglobulin to prevent CMV disease in CMV-seropositive heart transplant recipients treated with OKT3.

We compared the efficacy of ganciclovir versus that of cytomegalovirus (CMV) immunoglobulin for the prevention of CMV disease in 31 CMV-seropositive heart transplant recipients who had received early immunoprophylaxis with OKT3 monoclonal antibodies. The incidence of CMV disease and visceral involvement was much higher in the CMV immunoglobulin group than in the ganciclovir group (40 versus 6%, respectively; P = 0.03). No adverse effects were found in the CMV immunoglobulin group, but 19% of the patients in the ganciclovir group developed mild leukopenia or a mild increase in their serum creatinine levels.