International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

Chemotherapy of experimental streptococcal endocarditis. I. Comparison of commonly recommended prophylactic regimens.

The effectiveness of various antibiotics commonly recommended for the prophylaxis of bacterial endocarditis has been evaluated in experimental streptococcal endocarditis in rabbits. High doses of penicillin G did not prevent the development of this infection. The only consistently successful prophylactic regimens using penicillin alone were those which provided for both an early high serum level and more than 9 h of effective antimicrobial action. Vancomycin was the only other drug which proved uniformly successful when given alone, even though the duration of its antimicrobial action in the blood was only 3 h. However, combined therapy using penicillin G or ampicillin with streptomycin was always effective in prophylaxis. Treatment with single injections of ampicillin, cephaloridine, cephalexin, clindamycin, cotrimoxazole, rifampicin, streptomycin, erythromycin, and tetracycline failed to prevent infection. The findings provide information on the effect of antimicrobials in vivo and may be applicable to the chemoprophylaxis of infective endocarditis in clinical practice.

Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide.

Cryptococcus neoformans is variably encapsulated in vitro, whereas in tissues it develops a large capsule. We observed that cells of a strain with thin capsules, when growing in a standard fungal culture medium, became heavily encapsulated when incubated in serum-free cell culture medium (Dulbecco's modified Eagle's medium [DME]). Capsule size was quantitated physically by measuring cell volume, and chemically by determining the content of a capsular monosaccharide, glucuronate. The CO2/HCO-3 couple stimulated capsule development, resulting in visible enlargement by 3 h after exposure to high CO2/HCO-3. The amount of capsule per cell was directly proportional to the total millimolar CO2/HCO-3 concentration between 24 and 2.4 mM at pH 7.35, but at constant PCO2 (40 torr) and varying [HCO-3], the cells were heavily encapsulated down to pH 6.8. Concentration of CO2/HCO-3 in the physiologic range increased elaboration of polysaccharide into the medium and slowed the cell generation time from 2 to 6 h. Four other first-passage clinical isolates were all heavily encapsulated in DME with CO2/HCO-3, but variably encapsulated in DME without CO2/HCO-3. Exposure of yeast to increased CO2/HCO-3 caused a marked reduction in complement-mediated phagocytosis by mouse macrophages. A stable clone was isolated which contained capsular polysaccharide, but lacked the CO2-inducible phenotype. This clone was avirulent for steroid-treated rabbits. Thus, the prevailing CO2 concentration in mammalian tissues may be one stimulus for capsular polysaccharide synthesis. This could serve as an adaptive mechanism favoring parasite survival in the host.

Chemotherapy of experimental streptococcal endocarditis. II. Synergism between penicillin and streptomycin against penicillin-sensitive streptococci.

Bacterial endocarditis was produced by intravenous injection of Streptococcus viridans into rabbits with preexisting sterile endocardial vegetations. After 6 h had elapsed, bacteria in the vegetations could not be eradicated by brief treatment with antimicrobials to which the streptococci were sensitive. However, when treatment with penicillin was continued for 4 days, the animals were cured. The 6-h infection therefore offered a model in which treatments could be conveniently compared over a short period. Synergism was demonstrated between penicillin and streptomycin in endocarditis due to a fully penicillin-sensitive streptococcus, a point which had not been previously proved in vivo. The clinical implications are discussed.

Chemotherapy of experimental streptococcal endocarditis. IV. Further observations on prophylaxis.

The ability of antibiotics to prevent Streptococcus sanguis endocarditis was tested in rabbits. Only vancomycin or a combination of penicillin G plus streptomycin always prevented infection when administered as a single dose. A loading dose of 30 mg/kg of phenoxymethyl penicillin (penicillin V) followed by additional 7.5 mg/kg doses for 48 h proved to be the only successful prophylactic program that could be given orally to man. Cefazolin alone or with streptomycin in multiple doses was also an effective alternative to penicillin or penicillin derivatives. Erythromycin uniformly failed to protect animals from bacterial endocarditis but showed greater prophylactic efficacy when a low inoculum of streptococci was used.

Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages.

The microbiostatic action of macrophages was studied in vitro employing peritoneal cytotoxic macrophages (CM) from mice acting against Cryptococcus neoformans cultured in Dulbecco's medium with 10% dialyzed fetal bovine serum. Fungistasis was measured using electronic particle counting after lysis of macrophages with detergent. Macrophage fungistasis failed in medium lacking only L-arginine. Complete fungistasis was restored by L-arginine; restoration was concentration dependent, maximal at 200 microM. Deletion of all other essential amino acids did not abrogate fungistasis provided that L-arginine was present. Of twenty guanido compounds, including D-arginine, only three (L-arginine, L-homoarginine, and L-arginine methylester) supported fungistasis. Known activators or mediators of macrophage cytotoxicity (endotoxin, interferon gamma, tumor necrosis factor) did not replace L-arginine for CM-mediated fungistasis. The guanido analogue NG-monomethyl-L-arginine was a potent competitive inhibitor of CM-mediated fungistasis giving 50% inhibition at an inhibitor/L-arginine ratio of 1:27. Although CM completely blocked fungal reproduction via an L-arginine-dependent mechanism, the majority of the dormant fungi remained viable. Thus, this mechanism is viewed as a microbiostatic process similar or identical to the tumoristatic effect of macrophages. This suggests the production of a broad spectrum biostatic metabolite(s) upon consumption of L-arginine by cytotoxic macrophages.

Metabolic fate of L-arginine in relation to microbiostatic capability of murine macrophages.

L-arginine is required for the fungistatic action of murine macrophages in vitro. To further investigate this requirement, L-arginine metabolism by macrophages was measured under conditions where fungistasis either succeeded or failed. Macrophage fungistasis correlated with metabolism of L-arginine to citrulline, nitrite, and nitrate. The metabolic rate was dependent on extracellular L-arginine concentration, reaching a maximum of 67 nmol nitrite/h per mg protein. It accounted for one-third of arginine consumed by fungistatic macrophages. Equimolar amounts of citrulline and total nitrite plus nitrate accumulated in medium. This was consistent with the hypothesis that one of the equivalent guanidino nitrogens of L-arginine was oxidized to both nitrite and nitrate leaving L-citrulline as the amino acid reaction product. The analogue, NG-mono-methyl-L-arginine, selectively inhibited nitrogen oxidation and it was shown previously that it inhibited fungistatic capability. Resident macrophages were not fungistatic and their nitrogen oxidation was low. Once macrophages began producing nitrite/nitrate, protein synthesis was not required during the next 8 h for either fungistasis or nitrogen oxidation. Two-thirds of L-arginine consumption was due to macrophage arginase yielding L-ornithine and urea, which accumulated in medium. This activity was dissociated from macrophage fungistasis. Nitrogen oxidation metabolism by macrophages is linked to a mechanism that inhibits proliferation of fungi. This may involve synthesis of an intermediate compound(s) that has antimicrobial properties.

The neuroleptic malignant syndrome.

The neuroleptic malignant syndrome (NMS) comprises hyperpyrexia, altered consciousness, muscular rigidity, and autonomic dysfunction. It is a rare idiosyncratic reaction to major tranquilizers, including the phenothiazines, butyrophenones, and thioxanthenes; haloperidol and fluphenazine enanthate or fluphenazine decanoate are the drugs most commonly incriminated. The syndrome occurs after therapeutic rather than toxic doses of neuroleptic drugs and is unrelated to the duration of therapy. The NMS is attributed to a disturbance of dopaminergic systems within the basal ganglia and hypothalamus. Associated laboratory abnormalities include leukocytosis, with elevated serum creatine phosphokinase (CPK) and liver enzyme concentrations. The NMS, which is known to some psychiatrists and neurologists but to few internists, probably is underdiagnosed; therefore, its true incidence is unknown. The NMS should be included in the differential diagnosis of any febrile patient with a history of neuroleptic treatment. Because the mortality of NMS is about 20%, early diagnosis and withdrawal of the neuroleptic drug therapy is crucial. Supportive treatment in a medical intensive care unit may be required.

Intestinal parasites and HIV infection in Tanzanian children with chronic diarrhea.

OBJECTIVE: To determine whether specific intestinal parasites are associated with HIV infection in Tanzanian children with chronic diarrhea. DESIGN: A prospective, cross-sectional study. SETTING: Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania. SUBJECTS: All children aged 15 months to 5 years admitted with chronic diarrhea, and age-matched controls. METHODS: Standardized history, physical examination, HIV serology, and stool parasitology were evaluated for all subjects. We compared three groups: HIV-infected and non-HIV-infected children with chronic diarrhea and controls without diarrhea. MAIN OUTCOME MEASURES: Fecal parasites and nutritional status. RESULTS: Chronic diarrhea accounted for one-quarter of all cases of diarrheal disease in the defined age range, and children with chronic diarrhea were severely malnourished. Forty per cent of subjects with chronic diarrhea were HIV-seropositive. Although intestinal parasites were detected in approximately 50% of all three groups, diarrheagenic parasites were detected in up to 40% of children with chronic diarrhea. Blastocystis hominis was detected only in HIV-infected patients. CONCLUSIONS: HIV infection was common in children with chronic diarrhea, and parasitic agents of diarrhea may be important in children with chronic diarrhea both with and without HIV infection in this setting. B. hominis was more frequent in HIV-infected children. The immunocompromising effects of severe malnutrition may have diminished the difference between HIV-infected and non-HIV-infected children.

PIP: The authors attempted to determine whether specific intestinal parasites are associated with HIV infection in Tanzanian children with chronic diarrhea. This prospective, cross-sectional study included all children aged 15 months to 5 years admitted with chronic diarrhea and a group of age-matched controls and took place at Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania. Standardized history, physical examination, HIV serology, and stool parasitology were evaluated for all subjects. The authors compared 3 groups - HIV infected and non-HIV-infected children with chronic diarrhea and controls without diarrhea--and they measured fecal parasites and nutritional status. Chronic diarrhea accounted for one-fourth of all cases of diarrheal disease in the defined age range, and children with chronic diarrhea were severely malnourished. 40% of all subjects with chronic diarrhea were HIV-seropositive. Although intestinal parasites were detected in approximately 50% of all 3 groups, diarrheagenic parasites were detected in up to 40% of children with chronic diarrhea. Blastocystis hominis was detected only in HIV-infected patients. HIV infection was common in children with chronic diarrhea, and parasitic agents of diarrhea may be important in children with chronic diarrhea both with and without HIV infection in this setting. B. hominis was more frequent in HIV-infected children. The immunocompromising effects of severe malnutrition may have diminished the differences between HIV-infected and non-HIV-infected children.

Cryptococcemia.

Previous reports have emphasized that cryptococcemia is almost uniformly fatal. To define the clinical course and prognostic and therapeutic implications of cryptococcemia, we studied 15 patients treated at this medical center over the past 7 years. Cryptococcemia was strongly associated with corticosteroid therapy, especially when the dosage had recently been increased. Meningitis was common (but not invariably present) in these patients, characteristically with a large burden of organisms in the cerebrospinal fluid. Cryptococcemia developed during hospitalization in one-third of our patients; this high rate of nosocomial infection emphasizes that C. neoformans infection should be considered in febrile, immunocompromised patients even when the initial work-up is negative. Most of these patients were treated with amphotericin B plus 5-fluorocytosine. Although the one-year survival rate of 4/15 (29%) was dismal, no patient died from uncontrolled cryptococcal infection. Other infections, which developed before, during or after cryptococcemia was diagnosed, were the major immediate cause of morbidity and mortality. The progress of underlying diseases and the outcome of concomitant infections in these patients were more important determinants of survival than was cryptococcemia itself.

Single and multiple pyogenic liver abscesses. Natural history, diagnosis and treatment, with emphasis on percutaneous drainage.

The presenting features, modes of treatment and clinical course were reviewed for 55 patients with pyogenic liver abscess, seen at Duke University Medical Center over a 15-year period. Thirty-three patients had a solitary abscess and 22 had multiple abscesses. Most patients were between the ages of 40 and 60 years. Males predominated, 2.4:1. Major underlying conditions included biliary tract disease, malignancy and colonic disease. Eight patients, each with a solitary abscess, had no identifiable underlying condition. Symptoms and signs were nonspecific: fever, chills, focal abdominal tenderness and hepatomegaly were common. A raised serum alkaline phosphatase level was the most consistent abnormal laboratory finding. CT with contrast enhancement, radioisotope scanning and ultrasonography all accurately defined solitary hepatic abscesses. However, CT scan was more successful than other imaging techniques in detecting multiple abscesses. In seven patients the diagnosis was made only at laparotomy. Overall, a diagnosis of liver abscess was made in 50 living patients (91%). Microorganisms were recovered from pus and/or blood cultures of 44 patients (80%). Most common were enteric gram-negative facultative rods, anaerobic gram-negative rods, and microaerophilic streptococci. Single abscesses were more likely than multiple abscesses to contain more than one organism. All patients received antibiotics; the choice of antibiotic does not appear to be critical provided the regimen has a broad spectrum including activity against anaerobes. Surgical or percutaneous drainage was successful when attempted in all patients with a single abscess, but the outcome was less favorable in those with multiple abscesses. Percutaneous drainage is currently replacing open operative drainage as the method of choice. Overall mortality in patients with single abscesses was 15% (5/33) and in those with multiple abscesses 41% (9/22).

Current issues in prevention of infective endocarditis.

Prevention of infective endocarditis continues to concern health care providers in many specialties. The well-known lack of primary clinical trials in this area is not expected to change. Therefore, the evolution of recommendations and practice must be based on theoretic considerations and continuing assessment of secondary sources of information. Recent developments include a report of 52 cases in which antibiotic prophylaxis for infective endocarditis was attempted but appeared to fail. Most of these patients had undergone dental procedures after oral penicillin prophylaxis, with subsequent development of streptococcal endocarditis. In two thirds, the organism was sensitive to the antibiotic used. Notably, the most common underlying cardiac lesion among these patients was mitral valve prolapse. However, two recent independent analyses have concluded that providing endocarditis prophylaxis for all patients with mitral valve prolapse during procedures that might cause bacteremia would not be cost-effective. This is primarily because mitral valve prolapse is common and endocarditis is relatively rare, resulting in an adverse risk-benefit ratio. Parenteral prophylaxis for mitral valve prolapse might even cause a net loss of life from anaphylaxis. On the other hand, for the individual patient or physician, the reassurance provided by attempted prophylaxis with oral penicillin can be purchased at low cost and low risk. Very few cases of infective endocarditis have been reported after gastrointestinal and other endoscopic procedures; most of these do not need antibiotic coverage. Prophylactic antibiotics should be restricted to those situations in which both the procedure and the underlying cardiac condition seem to pose significant risk, for example, endoscopic sclerotherapy of esophageal varices in patients with prosthetic heart valves. Newly revised recommendations have been issued by the Medical Letter, the American Heart Association, and the American Dental Association. These regimens are shorter and simpler than earlier versions.

Prevention of central nervous system infections in patients at risk.

Infections of the central nervous system in patients at risk are relatively uncommon when compared with pneumonia, bacteremia, and soft tissue infection. However, they carry serious morbidity and are frequently fatal. Each of the diverse conditions that can place a patient at risk for central nervous system infection is associated with a fairly predictable spectrum of etiologic organisms. Various forms of trauma (including blunt and penetrating injuries and neurosurgery, especially when a cerebrospinal fluid shunt is implanted) predispose to infection with common pathogenic bacteria. Defects of cellular immunity including congenital immune deficiencies, immunosuppressive drug therapy, leukemia, lymphoma, and the acquired immune deficiency syndrome are more likely to give rise to infection with a distinctive spectrum of opportunistic viruses, fungi, and protozoa. Other underlying conditions include sinus, ear, and mastoid infections, congenital heart disease, intrathoracic suppuration, endocarditis, and bacteremia, hypogammaglobulinemia, and complement deficiencies. Some preventive measures including vaccines, antibiotics, and surgical procedures are available. However, for many of these central nervous system infections, preventive measures are lacking or less effective than those for infections in other organs. In the future, opportunistic central nervous system infections will increase in frequency as the number of patients at risk continues to grow.

Manifestations of human T-lymphotropic virus type I infection.

HTLV-I, the first human oncovirus, is a type C retrovirus linked to the development of ATLL. The virus shows a striking ethnogeographic distribution that is only partially understood. Certain populations at high risk for AIDS appear to have a higher incidence of HTLV-I infection. The extended latent period renders present knowledge of the sequelae and natural history of HTLV-I seropositivity incomplete, although recent data suggest that HTLV-I infection may have important implications for blood transfusion, organ transfer, and public health policy. A variety of clinical syndromes have been associated with infection, ranging from an asymptomatic carrier state to acute ATLL with lymphadenopathy, hepatosplenomegaly, hypercalcemia, cutaneous lesions, and systemic immunosuppression. Conventional chemotherapy is marginally effective; innovative approaches to therapy are presently being evaluated.

New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service.

PURPOSE: This study was designed to develop improved criteria for the diagnosis of infective endocarditis and to compare these criteria with currently accepted criteria in a large series of cases. PATIENTS AND METHODS: A total of 405 consecutive cases of suspected infective endocarditis in 353 patients evaluated in a tertiary care hospital from 1985 to 1992 were analyzed using new diagnostic criteria for endocarditis. We defined two "major criteria" (typical blood culture and positive echocardiogram) and six "minor criteria" (predisposition, fever, vascular phenomena, immunologic phenomena, suggestive echocardiogram, and suggestive microbiologic findings). We also defined three diagnostic categories: (1) "definite" by pathologic or clinical criteria, (2) "possible," and (3) "rejected." Each suspected case of endocarditis was classified using both old and new criteria. Sixty-nine pathologically proven cases were reclassified after exclusion of the surgical or autopsy findings, enabling comparison of clinical diagnostic criteria in proven cases. RESULTS: Fifty-five (80%) of the 69 pathologically confirmed cases were classified as clinically definite endocarditis. The older criteria classified only 35 (51%) of the 69 pathologically confirmed cases into the analogous probable category (p < 0.0001). Twelve (17%) pathologically confirmed cases were rejected by older clinical criteria, but none were rejected by the new criteria. Seventy-one (21%) of the remaining 336 cases that were not proven pathologically were probable by older criteria, whereas the new criteria almost doubled the number of definite cases, to 135 (40%, p < 0.01). Of the 150 cases rejected by older criteria, 11 were definite, 87 were possible, and 52 were rejected by the new criteria. CONCLUSION: Application of the proposed new criteria increases the number of definite diagnoses. This should be useful for more accurate diagnosis and classification of patients with suspected endocarditis and provide better entry criteria for epidemiologic studies and clinical trials.

Deficiency of the fifth component of complement in human subjects. Clinical, genetic and immunologic studies in a large kindred.

The discovery of a large kindred with a heritable deficiency of the fifth component of complement (C5) has permitted the accumulation of new clinical, genetic and immunologic data concerning the role of C5 in human subjects. The proband, who has had nine episodes of disseminated gonococcal infection, has a hemolytic C5 level of approximately 0.5 per cent of normal. No C5 protein was detectable, but low levels of functional C5 activity could be found using a sensitive bactericidal assay. The proband's twin as well as another sister also had extremely low levels of hemolytic C5(approximately 0.5 per cent normal), but both these subjects have been healthy. Hemolytic complement and bacteriolytic activity could be restored by the addition of purified C5. No chemotactic activity for polymorphonuclear leukocytes could be generated in the C5-deficient serums upon activation of either the classic or alternative pathways, again demonstrating the importance of C5 in human subjects for the production of chemotactic factors. The chemotactic responsiveness of the patients' polymorphonuclear leukocytes and monocytes to preformed chemotactic factors was not depressed. Twenty-two of 32 other family members from three generations had depressed whole hemolytic complement levels. In 19 of 30 family members, levels of hemolytic C5 ranged from 13 to 64 per cent of normal. No linkage for C5 deficiency and the A or B loci of the major histocompatibility complex could be found. These data suggest an autosomal codominant mode of inheritance of C5 deficiency. Deficiency of C5 is compatible with good health, but it can be associated with repeated disseminated gonococcal infection.

International health and internal medicine residency training: the Duke University experience.

OBJECTIVE: To evaluate the impact of the Duke University Medicine Residency International Health Program (IHP) on program participants and to evaluate the relationship of the IHP to the residency program. SUBJECTS AND METHODS: The Duke University Medicine Residency Program classes of 1988 to 1996 participated in a questionnaire-based survey. All program participants (n = 59), a group of nonparticipants (n = 138), and residents who had not yet had an opportunity to participate (preparticipants; n = 106). RESULTS: The overall response rate to the questionnaire was 93%. Participation exceeded expectations and had a strongly positive impact on personal and professional lives of the majority of the participants. Participants reported a significant positive impact on their training in internal medicine and their knowledge of tropical medicine. A minority of nonparticipants identified a positive effect in these areas due to conferences and interactions with their participating colleagues. Participants who changes career plans during residency tended to move toward areas of general internal medicine or public health, in contrast to nonparticipants who tended to change areas of subspecialty or chose private practice. The IHP was identified as a significant factor for selection of the Duke Medicine Residency by 42% of the preparticipant group. Nearly all of the respondents (99%) indicated that the IHP should be continued. CONCLUSION: The IHP has a measurable positive impact on the participants, as well as on the Medicine Residency Program.

Intravenous acyclovir therapy of first episodes of genital herpes: a multicenter double-blind, placebo-controlled trial.

PURPOSE: A collaborative multicenter double-blind, placebo-controlled trial of intravenous acyclovir treatment of first-episode genital herpes was performed in order to substantiate previous findings on the efficacy and safety of this drug, to evaluate the influence of parenteral therapy on recurrence frequency, and to obtain further data on the natural history of genital herpes. PATIENTS AND METHODS: Eighty-two patients with first episodes of genital herpes simplex virus (HSV) infection were randomly assigned in a double-blind fashion to treatment with intravenous acyclovir (5 mg/kg every eight hours) or placebo for five days. Before therapy, all lesions in the genital/perineal area and in extragenital sites were cultured. New lesions appearing in both areas after the onset of therapy were cultured separately. Lesions in all groups were cultured until completely healed. Sera were collected from all patients on entry to the study and on Day 21 to determine presence or absence of antibodies to HSV-1 and HSV-2. Time to healing, time to crusting, time to cessation of viral shedding, and appearance of new lesions during therapy were compared for each treatment group. RESULTS: Patients receiving acyclovir experienced a significant reduction in the median duration of pain (4.3 versus 4.8 days, p = 0.019), viral shedding (1.9 versus 8.4 days, p less than 0.001), and time to healing (8.4 versus 11.5 days, p = 0.02) compared with placebo recipients. These differences were largely attributable to the effect of therapy in the subset of patients with primary disease in whom acyclovir reduced the median duration of pain from 10.6 days to 4.2 days, the median duration of viral shedding from 17.1 days to 1.9 days, and the median time to healing from 14.2 days to 8.3 days. The rate of subsequent recurrence of genital herpes was not altered by acyclovir treatment: 24 of 32 acyclovir recipients (75 percent) experienced one or more recurrences during a mean follow-up of 14 months compared with 19 of 27 placebo recipients (70 percent). Among patients experiencing recurrences, the mean number of recurrences per month among acyclovir recipients was 0.25 compared with 0.19 for patients given placebo. CONCLUSION: This multicenter trial confirms the efficacy of intravenous acyclovir in the management of first-episode genital herpes, especially in patients with primary infection. However, therapy did not alter the frequency of recurrences.

Multicenter collaborative trial of intravenous acyclovir for treatment of mucocutaneous herpes simplex virus infection in the immunocompromised host.

Intravenous acyclovir was evaluated in the treatment of 97 immunocompromised patients with mucocutaneous herpes simplex virus infection in a randomized, double-blind, placebo-controlled trial. Acyclovir recipients had significantly shorter periods of virus shedding (p less than 0.0002) and lesion pain (p less than 0.01), and more rapid lesion scabbing (p less than 0.004) and lesion healing (p less than 0.04). The most common adverse reaction was a low incidence of peripheral vein irritation; no serious toxicity could be definitely attributed to acyclovir treatment even in these seriously ill patients. Intravenous acyclovir offers both safe and effective treatment for mucocutaneous herpes simplex virus infection in the immunocompromised host.

Negative predictive value of the Duke criteria for infective endocarditis.

With use of new Duke criteria, 405 episodes of suspected endocarditis were previously classified as "definite," "possible," or "rejected" endocarditis. To determine the negative predictive value of the Duke clinical criteria for the classification of suspected endocarditis, chart review and follow-up were performed for the 52 episodes in which the diagnosis of endocarditis was rejected. Three of 52 episodes were reclassified to possible endocarditis; 49 episodes in 48 patients met the criteria for rejected endocarditis. Of these 49 episodes, 31 (63%) had a firm alternate diagnosis other than endocarditis, 17 (35%) had resolution of the clinical syndrome leading to the suspicion of endocarditis with < or = 4 days of antibiotics, and 1 patient had no evidence of endocarditis at surgery. Echocardiograms recorded in 3 patients with rejected endocarditis had evidence of oscillating valvular masses, and blood cultures were positive in 13 episodes; none of these patients had evidence of endocarditis at follow-up. Follow-up or outcome information was available in all 49 episodes. Excluding the 5 in-hospital deaths, mean duration (+/- SD) of follow-up was 39.9 +/- 28.8 months (range 0.5 to 108.0); in living patients, mean time to final follow-up was 56.2 +/- 25.2 months (range 25.0 to 108.0). One patient had possible infective endocarditis at autopsy. No patient in our series whose diagnosis of endocarditis had been rejected had proven endocarditis. Therefore, the negative predictive value of the Duke clinical criteria for endocarditis is at least 92%.