Identification and evaluation of outcome measurement instruments in pyoderma gangrenosum: a systematic review.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare autoinflammatory skin condition that causes tissue destruction and subsequent painful ulcers. To date, there are no core domains or instruments for assessing PG severity in clinical trials, and current treatment paradigms rely on outcome measurements that have not been well characterized in the literature. OBJECTIVES: To perform two systematic reviews that (i) identify the outcome measurement instruments used in PG clinical trials and their corresponding domains and (ii) identify any associated validation studies and evaluate their measurement properties and methodological quality. METHODS: We systematically searched the MEDLINE and Embase databases for PG outcome measurement instruments. We also systematically searched for PG instrument validation studies. We evaluated the measurement properties and methodological quality of validation studies using the 2018 COSMIN Risk of Bias checklist. RESULTS: In total, seven clinical trials were included. These studies utilized a total of 20 different instruments, including 11 physician-reported instruments, eight patient-reported instruments and one composite instrument. Among these, 85% of the instruments lacked any validation data. Of the remaining three validated instruments (speed of healing, physician global assessment and resolution of inflammation), methodological quality was not available for half of the COSMIN categories. CONCLUSIONS: We identified 17 non-validated outcome measurement instruments used in PG clinical trials. We conclude that PG validation studies are required for existing instruments, and new instruments need to be developed to inform the consensus process for the development of a core outcome set for PG. What is already known about this topic? Pyoderma gangrenosum (PG) is a rare autoinflammatory skin condition that has been characterized by multiple outcome measurement instruments in clinical trials. However, there is no consensus on the most validated and appropriate outcome measurement instruments. What does this study add? This study identifies and evaluates 20 unique outcome measurement instruments for PG in the literature. Of these 20, 17 lack any instrument validation data, highlighting the need for future studies. What are the clinical implications of this work? Despite the current use of several outcome measurement instruments, future studies should explore the validation surrounding these instruments, as no instruments can currently be recommended.

Experimental vaccine induces Th1-driven immune responses and resistance to Neisseria gonorrhoeae infection in a murine model.

Female mice were immunized intravaginally with gonococcal outer membrane vesicles (OMVs) plus microencapsulated interleukin-12 (IL-12), and challenged using an established model of genital infection with Neisseria gonorrhoeae. Whereas sham-immunized and control animals cleared the infection in 10-13 days, those immunized with OMV plus IL-12 cleared infection with homologous gonococcal strains in 6-9 days. Significant protection was also seen after challenge with antigenically distinct strains of N. gonorrhoeae, and protective anamnestic immunity persisted for at least 6 months after immunization. Serum and vaginal immunoglobulin G (IgG) and IgA antibodies were generated against antigens expressed by homologous and heterologous strains. Iliac lymph node CD4+ T cells secreted interferon-γ (IFNγ), but not IL-4, in response to immunization, and produced IL-17 in response to challenge regardless of immunization. Antigens recognized by immunized mouse serum included several shared between gonococcal strains, including two identified by immunoproteomics approaches as elongation factor-Tu (EF-Tu) and PotF3. Experiments with immunodeficient mice showed that protective immunity depended upon IFNγ and B cells, presumably to generate antibodies. The results demonstrated that immunity to gonococcal infection can be induced by immunization with a nonliving gonococcal antigen, and suggest that efforts to develop a human vaccine should focus on strategies to generate type 1 T helper cell (Th1)-driven immune responses in the genital tract.

STI/HIV Sexual Risk Behavior and Prevalent STI Among Incarcerated African American Men in Committed Partnerships: The Significance of Poverty, Mood Disorders, and Substance Use.

African Americans face disproportionate sexually transmitted infection including HIV (STI/HIV), with those passing through a correctional facility at heightened risk. There is a need to identify modifiable STI/HIV risk factors among incarcerated African Americans. Project DISRUPT is a cohort study of incarcerated African American men recruited from September 2011 through January 2014 from prisons in North Carolina who were in committed partnerships with women at prison entry (N = 207). During the baseline (in-prison) study visit, participants responded to a risk behavior survey and provided a urine specimen, which was tested for STIs. Substantial proportions reported multiple partnerships (42 %), concurrent partnerships (33 %), and buying sex (11 %) in the 6 months before incarceration, and 9 % tested positive for an STI at baseline (chlamydia: 5.3 %, gonorrhea: 0.5 %, trichomoniasis: 4.9 %). Poverty and depression appeared to be strongly associated with sexual risk behaviors. Substance use was linked to prevalent STI, with binge drinking the strongest independent risk factor (adjusted odds ratio: 3.79, 95 % CI 1.19-12.04). There is a continued need for improved prison-based STI testing, treatment, and prevention education as well as mental health and substance use diagnosis.

Antimicrobial susceptibility and molecular typing of MRSA in cystic fibrosis.

OBJECTIVES: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in cystic fibrosis (CF) patients in the United States is approximately 25%. Little is known about the relative proportion of hospital- versus community-associated strains or the antimicrobial susceptibility of MRSA in different CF centers. We hypothesized that the majority of MRSA isolates obtained from children with CF are those endemic in the hospital and that those associated with community acquisition (SCCmec IV) would be more resistant than typically seen in non-CF MRSA isolates. METHODS: We studied MRSA strains from seven pediatric CF centers to determine the clonal distribution based on DNA sequencing of the staphylococcal protein A gene (spa typing), the type of staphylococcal chromosomal cassette mec (SCCmec), and the proportion of strains with Panton-Valentine leukocidin (PVL). Antimicrobial susceptibility to systemic and topical antibiotics was compared between different MRSA types. RESULTS: We analyzed 277 MRSA isolates from unique patients (mean age 11.15 ± 4.77 years, 55% male). Seventy % of isolates were SCCmec II PVL negative and the remainder SCCmec IV. Overall 17% MRSA strains were PVL positive (all SCCmec IV). Spa typing of 118 isolates showed most of the SCCmec II strains being t002, while SCCmec IV PVL positive isolates were t008, and SCCmec IV PVL negative isolates represented a variety of spa-types. The proportions of SCCmec II strains and spa-types were similar among centers. Overall rates of resistance to trimethoprim-sulfamethoxazole (4%), tetracycline (7%), tigecycline (0.4%), linezolid (0.4%) as well as fosfomycin (0.4%), fusidic acid (3%), and mupirocin (1%) were low. No strains were resistant to vancomycin. SCCmec II strains had higher rates of resistance to ciprofloxacin and clindamycin (P < 0.001) than SCCmec IV strains. CONCLUSIONS: In this U.S. study, most MRSA isolates in the pediatric CF population were SCCmec II PVL negative. Rates of resistance were low, including to older and orally available antibiotics such as trimethoprim-sulfamethoxazole.

High HIV prevalence among men who have sex with men in Jamaica is associated with social vulnerability and other sexually transmitted infections.

BACKGROUND: Human immunodeficiency virus (HIV) prevalence among men who have sex with men (MSM) is thought to be high in Jamaica. The objective of this study was to estimate HIV prevalence and identify risk factors in order to improve prevention approaches. METHODS: With the help of influential MSM, an experienced research nurse approached MSM in four parishes to participate in a cross-sectional survey in 2007. Men who have sex with men were interviewed and blood taken for HIV and syphilis tests, and urine taken for gonorrhoea, chlamydia and trichomonas testing using transcription-mediated amplification assays. A structured questionnaire was administered by the nurse. RESULTS: One third (65 of 201; 32%, 95% Confidence Interval (CI) 25.2, 47.9) of MSM were HIV positive. Prevalence of other sexually transmitted infections (STI) was: chlamydia 11%, syphilis 6%, gonorrhoea 3.5% and trichomonas 0%. One third (34%) of MSM identified themselves as being homosexual, 64% as bisexual and 1.5% as heterosexual. HIV positive MSM were significantly more likely to have ever been told by a doctor that they had an STI (48% vs 27%, OR 2.48 CI 1.21, 5.04, p = 0.01) and to be the receptive sexual partner at last sex (41% vs 23%, OR 2.41 CI 1.21, 4.71, p = 0.008). Men who have sex with men who were of low socio-economic status, ever homeless and victims of physical violence were twice as likely to be HIV positive. The majority (60%) of HIV positive MSM had not disclosed their status to their partner and over 50% were not comfortable disclosing their status to anyone. CONCLUSIONS: The high HIV prevalence among MSM is an important factor driving the HIV epidemic in Jamaica. More effective ways need to be found to reduce the high prevalence of HIV among MSM including measures to reduce their social vulnerability, combat stigma and discrimination and empower them to practice safe sex.

Validity of self-reported 'safe sex' among female sex workers in Mombasa, Kenya--PSA analysis.

We assessed the validity of self-reported sex and condom use by comparing self-reports with prostate-specific antigen (PSA) detection in a prospective study of 210 female sex workers in Mombasa, Kenya. Participants were interviewed on recent sexual behaviours at baseline and 12-month follow-up visits. At both visits, a trained nurse instructed participants to self-swab to collect vaginal fluid specimens, which were tested for PSA using enzyme-linked immunosorbent assay (ELISA). Eleven percent of samples (n = 329) from women reporting no unprotected sex for the prior 48 hours tested positive for PSA. The proportions of women with this type of discordant self-reported and biological data did not differ between the enrolment and 12-month visit (odds ratio [OR] 1.1; 95% confidence interval [CI] 0.99, 1.2). The study found evidence that participants failed to report recent unprotected sex. Furthermore, because PSA begins to clear immediately after exposure, our measures of misreported semen exposure likely are underestimations.

Trichomoniasis: clinical manifestations, diagnosis and management.

Trichomonas vaginalis was originally considered a commensal organism until the 1950s when the understanding of its role as a sexually transmitted infection (STI) began to evolve. Trichomoniasis has been associated with vaginitis, cervicitis, urethritis, pelvic inflammatory disease (PID), and adverse birth outcomes. Infection with T vaginalis could have an important role in transmission and acquisition of HIV. T vaginalis is site specific for the genitourinary tract and has been isolated from virtually all genitourinary structures. Asymptomatic disease is common in both men and women, thus screening for disease is important. Various sociodemographic factors have been correlated with presence of T vaginalis, and may be used to predict infection. Diagnosis is usually made from wet mount microscopy and direct visualisation, which are insensitive. DNA amplification techniques perform with good sensitivity, but are not yet approved for diagnostic purposes. In areas where diagnostic methods are limited, management of trichomoniasis is usually as part of a clinical syndrome; vaginal discharge for women and urethral discharge for men. A single dose of metronidazole is effective in the majority of cases. Outside of the United States, other nitroimidazoles may be used and are as effective as metronidazole. Metronidazole resistance is an emerging problem, but its clinical importance is not yet clear. Concomitant treatment of sexual partners is recommended.

Selection for expression of the gonococcal hemoglobin receptor during menses.

All gonococci encode a hemoglobin (Hgb) receptor, but it is phase variable, and most laboratory and clinical isolates are in the Hgb receptor "off" phase. In the present study, we address the question of whether there is a selective advantage to expressing the Hgb receptor during early phases of the menstrual cycle, when Hgb is readily available from menstrual blood. Inclinical isolates collected from women, Hgb use in vitro (Hgb receptor "on" phase) was associated with a shorter time since the onset of the last menstrual cycle, (P=.031, Wilcoxon rank-sum test). Thus, there may be a selective advantage to expression of the gonococcal Hgb receptor during infection of women in the early phases of their menstrual cycles.

Trichomonas vaginalis as a cause of urethritis in Malawian men.

BACKGROUND AND OBJECTIVES: Trichomonas vaginalis is one of the most common sexually transmitted infections. In Malawi, rates of trichomoniasis in women are high. The prevalence of T. vaginalis infection in men is expected to be high but has not previously been documented. GOALS: We sought to determine the prevalence of trichomoniasis in Malawian men with and without urethritis, to evaluate a polymerase chain reaction detection assay for T. vaginalis in urethral swabs and to examine the effect of T. vaginalis infection on excretion of human immunodeficiency virus (HIV) in semen. STUDY DESIGN: Men presenting at the Sexually Transmitted Diseases (STD) and Dermatology Clinics in Malawi were enrolled in a cross-sectional study. We compared a polymerase chain reaction-based test for T. vaginalis detection with wet-mount microscopy and culture of urethral swabs. HIV serology was determined by enzyme-linked immunosorbent assay (ELISA), and HIV-1 RNA concentrations in semen were measured by quantitative nucleic acid sequence-based analysis. RESULTS: T. vaginalis was detected in 51 of 293 men. The estimated prevalence among symptomatic men was 20.8% and among asymptomatic men, 12.2%. Polymerase chain reaction performed with a sensitivity of 0.82 (95% CI: 0.66-0.92) and specificity of 0.95 (95% CI: 0.91-0.97) compared to wet-mount microscopy and culture. There was no difference in the rate of HIV seropositivity in men with and without T. vaginalis infection. However, in men with symptomatic urethritis, the median HIV RNA concentration in seminal plasma from men with T. vaginalis was significantly higher that in seminal plasma from HIV-positive men without trichomonas.

PIP: This study was conducted to determine the prevalence of trichomoniasis in Malawian men, to evaluate a polymerase chain reaction (PCR) detection assay for T. vaginalis in urethral swab samples, and to examine the effect of T. vaginalis infection on HIV excretion in the semen. There were 206 men with symptomatic urethritis in STD clinic and 127 asymptomatic men in the Dermatology Clinic who were enrolled from January to March 1996. Results, according to a wet-mount microscopy and urethral swabs culture combination, showed that, of 293 men, only 38 (13%) men were positive for T. vaginalis. The estimated prevalence among symptomatic and asymptomatic cases was 15.7% and 8.7%, respectively. The PCR yielded a sensitivity of 0.82 (95% CI: 0.66-0.92) and specificity of 0.95 (95% CI: 0.91-0.97); these were compared to the wet-mount microscopy and culture combination. Overall HIV seroprevalence of men was 51%, because gonococcal urethritis was shown to significantly increase seminal HIV RNA levels. The median HIV RNA concentration in seminal plasma from men with symptomatic urethritis plus T. vaginalis infection was significantly higher than in seminal plasma from HIV-positive men with symptomatic urethritis only. Since this study has several important limitations, a randomized clinical trial would be useful for determining whether urethritis cure rates can be significantly improved.

Molecular typing of Neisseria gonorrhoeae causing repeated infections: evolution of porin during passage within a community.

Thirty-three Neisseria gonorrhoeae isolates from 15 persons infected multiple times with the same serovar were compared using por gene sequencing, opa-typing, and arbitrarily primed-polymerase chain reaction. All three molecular techniques were more discriminatory than serotyping and identified differences between some isolates belonging to the same serovar. Although there were differences among Por sequences within some serovars, 10 of 15 subjects became reinfected with gonococci expressing identical Por proteins. Sequence analysis of por genes revealed evidence of horizontal genetic exchange and point mutations in potential surface-exposed regions during passage in the community.

Haemophilus ducreyi infection causes basal keratinocyte cytotoxicity and elicits a unique cytokine induction pattern in an In vitro human skin model.

Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid. Predominantly a cutaneous pathogen, H. ducreyi is present in chancroid ulcers that are characterized by extensive neutrophil accumulation in intraepidermal lesions accompanied by a mononuclear infiltrate in the dermis. We used an in vitro human skin model composed of foreskin fibroblasts and keratinocytes to examine host skin cell interactions with H. ducreyi 35000. Bacteria replicated and persisted in artificial skin for at least 14 days. We observed H. ducreyi inside suprabasal keratinocytes using transmission electron microscopy. Although no bacteria were seen in the basal keratinocyte region, these cells were disrupted in infected cocultures. H. ducreyi infection stimulated increased secretion of interleukin-6 (IL-6) and IL-8 by skin cells. Conversely, tumor necrosis factor alpha and IL-1alpha levels were not elevated. IL-8 produced in response to H. ducreyi infection may be involved in recruiting polymorphonuclear leukocytes and other inflammatory cells, thereby contributing to the tissue necrosis and ulcer formation characteristic of chancroid.

The transferrin receptor expressed by gonococcal strain FA1090 is required for the experimental infection of human male volunteers.

Iron, an essential nutrient for most microorganisms, is sequestered by the host to decrease the concentration of iron available to bacterial pathogens. Neisseria gonorrhoeae, the causative agent of gonorrhoea, can acquire iron by direct interaction with human iron-binding proteins, including the serum glycoprotein, transferrin. Iron internalization from host transferrin requires the expression of a bacterial receptor, which specifically recognizes the human form of transferrin. Two gonococcal transferrin-binding proteins have been implicated in transferrin receptor function, TbpA and TbpB. We constructed a gonococcal transferrin receptor mutant without the introduction of additional antibiotic resistance markers and tested its ability to cause experimental urethritis in human male volunteers. The transferrin receptor mutant was incapable of initiating urethritis, although the same inoculum size of the wild-type parent strain, FA1090, causes urethritis in >90% of inoculated volunteers. To our knowledge, this is the first experimental demonstration that a bacterial iron acquisition system is an essential virulence factor for human infection.

Periplasmic copper-zinc superoxide dismutase protects Haemophilus ducreyi from exogenous superoxide.

Haemophilus ducreyi causes chancroid, a sexually transmitted genital ulcer disease implicated in increased heterosexual transmission of HIV. As part of an effort to identify H. ducreyi gene products involved in virulence and pathogenesis, we created random TnphoA insertion mutations in an H. ducreyi 35000 library cloned in Escherichia coli. Inserts encoding exported or secreted PhoA fusion proteins were characterized by DNA sequencing. One such clone encoded a Cu-Zn superoxide dismutase (SOD) enzyme. The Cu-Zn SOD was periplasmic in H. ducreyi and accounted for most of the detectable SOD activity in whole-cell lysates of H. ducreyi grown in vitro. To investigate the function of the Cu-Zn SOD, we created a Cu-Zn SOD-deficient H. ducreyi strain by inserting a cat cassette into the sodC gene. The wild-type and Cu-Zn SOD null mutant strains were equally resistant to excess cytoplasmic superoxide induced by paraquat, demonstrating that the Cu-Zn SOD did not function in the detoxification of cytoplasmic superoxide. However, the Cu-Zn SOD null strain was significantly more susceptible to killing by extracellular superoxide than the wild type. This result suggests that the H. ducreyi Cu-Zn SOD may play a role in bacterial defence against oxidative killing by host immune cells during infection.

Organization of the Haemophilus ducreyi 35000 chromosome.

A physical and rudimentary genetic map of the Haemophilus ducreyi strain 35000 genome was constructed. Pulsed-field gel electrophoresis was used to separate restriction fragments of H. ducreyi DNA digested with Sfil, I-Ceul, or Sfil plus I-Ceul. The sizes of the fragments were determined, and the circular chromosome was estimated to be 1757 kbp. The six I-Ceul fragments and four Sfil fragments were ordered into macrorestriction maps using Southern blot hybridization with random H. ducreyi clones as probes. It was shown that both H. ducreyi and the distantly related Haemophilus influenzae have six rrn operons marked by the locations of the I-Ceul sites. However, the two species displayed distinct I-Ceul restriction patterns. A second H. ducreyi strain, CIP542, displayed an identical I-Ceul pattern to that of H. ducreyi 35000, but Sfil digests of teh two strains were distinct. The orientation of the six rrn operons was determined and thirteen identified H. ducreyi genes positioned on the map of strain 35000.

Swine model of Haemophilus ducreyi infection.

Haemophilus ducreyi is a strict human pathogen that causes sexually transmitted genital ulcer disease. We infected domestic swine with H. ducreyi 35000, resulting in the development of cutaneous ulcers histologically resembling human chancroid lesions. Intraepidermal lesions progressed from pustules to ulcers containing polymorphonuclear leukocytes and were accompanied by a dermal inflammatory infiltrate containing T cells and macrophages. H. ducreyi was recovered from lesions up to 17 days after inoculation, and pigs did not develop immunity to reinfection with the challenge strain. Features of the model include inoculation through abrasions in the epidermis, ambient housing temperatures for infected pigs, the ability to deliver multiple different inocula to a single host, and the availability of monoclonal antibodies against porcine immune cells permitting immunohistochemical characterization of the host immune response to H. ducreyi infection.

Microevolution within a clonal population of pathogenic bacteria: recombination, gene duplication and horizontal genetic exchange in the opa gene family of Neisseria meningitidis.

Opacity (Opa) proteins are a family of antigenically variable outer-membrane proteins of Neisseria meningitidis. Even among clonally related epidemic meningococcal isolates, there is greater variation of Opa protein expression than can be accounted for by the opa gene repertoire of any individual strain. We characterized the opa genes of eight closely related isolates of serogroup A N. meningitidis (subgroup IV-1) from a recent meningitis epidemic in West Africa. DNA sequence analysis and Southern blot experiments indicated that changes occurred in the opa genes of these bacteria as they spread through the human population, over a relatively short period of time. Such changes in one or a few loci within a clonal population are referred to as microevolution. The distribution of sequences present in hypervariable (HV) regions of the opa genes suggests that duplication of all or part of opa genes into other opa loci changed the repertoire of Opa proteins that could be expressed. Additional variability in this gene family appears to have been introduced by horizontal exchange of opa sequences from other meningococcal strains and from Neisseria gonorrhoeae. These results indicate that processes of recombination and genetic exchange contributed to variability in major surface antigens of this clonal population of pathogenic bacteria.

Characterization of the opa (class 5) gene family of Neisseria meningitidis.

Class 5 outer membrane proteins of Neisseria meningitidis show both phase- and antigenic variation of expression. The proteins are encoded by a family of opa genes that share a conserved framework interspersed with three variable regions, designated the semivariable (SV) region and hypervariable regions 1 (HV1) and 2 (HV2). In this study, we determined the number and DNA sequence of all of the opa genes of meningococcal strain FAM18, to assess the structural and antigenic variability in the family of proteins made by one strain. Pulsed field electrophoresis and Southern blotting showed that there are four opa genes in the FAM18 chromosome, and that they are not tightly clustered. DNA sequence analysis of the four cloned genes showed a modest degree of diversity in the SV region and more extensive differences in the HV1 and HV2 regions. There were four versions of HV1 and three versions of HV2 among the four genes. Each of the FAM18 opa loci contained a gene with a unique combination of SV, HV1, and HV2 sequences. We used lambda gt11 cloning and synthetic peptides to demonstrate that HV2 sequences completely encode the epitopes for two monoclonal antibodies specific for different class 5 proteins of FAM18.

Opsonic activity of cerebrospinal fluid in experimental cryptococcal meningitis.

The role of antibody in protection against infection with Cryptococcus neoformans is undefined. In this paper we describe the development of opsonic activity in the cerebrospinal fluid (CSF) of rabbits in response to cryptococcal meningitis. The opsonin appeared to be immunoglobulin G (IgG); the activity was heat stable, copurified with the IgG fraction during protein A separation, and could be absorbed by encapsulated cryptococci. Immunosuppression with cyclosporine could be administered to prevent or allow in vivo deposition of IgG on the polysaccharide capsule of yeast in the CSF. Both early and late cyclosporine regimens resulted in prolonged, severe meningeal infections corresponding to the complete absence of in vitro opsonic activity in the CSF. While the production of opsonic antibody is part of the successful host response against C. neoformans in the central nervous system of rabbits, the presence of specific immunoglobulin by itself is insufficient for complete protection.

Complementation of an Escherichia coli proC mutation by a gene cloned from Treponema pallidum.

Little is known concerning the biosynthetic and metabolic capabilities of the syphilis agent, Treponema pallidum, because of the inability to cultivate continuously the organism in vitro. To circumvent the problem of cultivation, researchers have used recombinant DNA technology to express treponemal protein antigens in Escherichia coli. However, with a few notable exceptions, the specific cellular roles of these cloned treponemal proteins have not been determined. In this study, a cosmid library of T. pallidum genomic DNA was constructed and amplified by repackaging infective lambda bacteriophage particles in vivo. Recombinant clones capable of complementing a null mutation in the E. coli proC gene encoding 1-pyrroline-5-carboxylate (P5C) reductase (EC 1.5.1.2) were subsequently identified. The complementing activity was eventually localized to a 2.3-kilobase BglII-HindIII fragment that hybridized to the same-size fragment of a BglII-HindIII digest of T. pallidum DNA. Two proteins of 41 and 27 kilodaltons (kDa) were encoded by this fragment, as determined by maxicell analysis. Although only the 41-kDa protein could be specifically precipitated by experimental syphilitic rabbit antisera, it was the 27-kDa protein that was responsible for the proC-complementing activity. The recombinant P5C reductase differed from the native E. coli enzyme by a number of biochemical properties. The cloning of a T. pallidum gene encoding P5C reductase strongly suggests that this pathogen has the ability to synthesize proline and possibly other amino acids.

Treatment of experimental disseminated candidiasis with cilofungin.

The efficacy of cilofungin treatment of experimental disseminated candidiasis in rabbits was examined. Cilofungin treatment reduced yeast counts, especially in the kidney, with activity comparable to that of amphotericin B. The peak level of cilofungin in serum was measured at 5 min after administration of a single dose, with no drug detectable after 90 min.