Clinical Infectious Diseases (Clin Infect Dis)

Landmark studies on the dynamics of HIV-1 infection, conducted nearly a decade ago, provided the theoretical framework on which the modern approach to combination antiretroviral therapy is based [1]. It is now accepted dogma that the high turnover rate of the virus, coupled with a high mutation rate—a consequence of the low fidelity of reverse transcriptase—leads to the accumulation of mutations in the viral quasispecies over time. According to this model, individual drug-resistance mutations are represented many times in the quasispecies; doublemutants are less common, and specific triple mutants are relatively rare [2]. Antiretroviral regimens consisting of several drugs with nonoverlapping resistance patterns erect a genetic barrier to resistance, because multiple mutations—which are unlikely to be preexisting in any single viral genome—are needed to reduce activity of the regimen. Because the level of plasma HIV-1 RNA at steady state is a function of the replication rate and because the replication rate is a determinant of the mutation rate, it is reasonable to assume that patients with high plasma HIV-1 RNA levels are more likely to harbor preexisting drug-resistant variants than are patients with lower virus loads. Likewise, patients with advanced HIV-1 disease may be at greater risk for the development of drug-resistant virus. In such patients, the genetic barrier of triple combination therapy might not suffice to prevent emergence of resistance and ensure durable suppression of virus replication. Indeed, for certain 3-drug combination regimens, high virus load and low CD4 cell count are associated with a greater risk of treatment failure [3].

A multicenter prospective, randomized, controlled trial, with 0.5% tincture of chlorhexidene versus 10% povidone-iodine as cutaneous antisepsis for central venous catheter (CVC) insertion, was conducted for patients in intensive care units. Of 374 patients, 242 had a CVC inserted for >3 days and were used for the primary analysis. Outcomes included catheter-related bacteremia, significant catheter colonization (⩾15 colony-forming units [cfu]), exit-site infection, serial quantitative exit-site culture (every 72 h), and molecular subtyping of all isolates. Patients in both study groups were comparable with respect to age, sex, underlying disease, length of hospitalization, reason for line insertion, and baseline APACHE II score. Documented catheter-related bacteremia rates were 4.6 cases per 1000 catheter-days in the chlorhexidine group (n = 125) and 4.1 cases per 1000 catheter-days in the povidone-iodine group (n = 117; not significant [NS]). Significant catheter-tip colonization occurred in 24 (27%) of 88 patients in the povidone-iodine group and in 31 (34%) of 92 patients in the chlorhexidine group (NS). A mean exit-site colony count of 5.9 × 105 cfu/mL per 25 cm2 of the surface area of skin in the povidone-iodine group versus 3.1 × 105 cfu/mL per 25 cm2 in the chlorhexidine group (NS) was found. There was a trend toward fewer exit-site infections in the chlorhexidine group (0 of 125 patients) versus those in the povidone-iodine group (4 of 117 patients; P = .053). Results of an intention-to-treat analysis were unchanged from the primary analysis. No difference was demonstrable between 0.5% tincture of chlorhexidine and 10% povidone-iodine when used for cutaneous antisepsis for CVC insertion in patients in the intensive care unit.

This double-blind, randomized, multicenter trial compared clindamycin/primaquine (Cm/Prq) with trimethoprim-sulfamethoxazole (TMP-SMZ) as therapy for AIDS-related Pneumocystis carinii pneumonia (PCP). Forty-five patients received clindamycin (450 mg four times daily [q.i.d.]) and primaquine (15 mg of base/d); 42 received TMP-SMZ (320 mg/1,600 mg q.i.d. if weight of ⩾60 kg or 240 mg/1,200 mg q.i.d. if weight of <60 kg) plus placebo primaquine. Overall, the efficacy of Cm/Prq was similar to that of TMP-SMZ (success rate, 76% vs. 79%, respectively); Cm/Prq was associated with fewer adverse events (P = .04), less steroid use (P = .18), and more rashes (P = .07). These differences were even greater for patients with PaO2 of >70 mm Hg (P = .02, P = .04, and P = .02, respectively). For patients with PaO2 of ⩽70 mm Hg (23 Cm/Prq recipients and 21 TMP-SMZ recipients), the efficacy of Cm/Prq was similar to that of TMP-SMZ (success rate, 74% vs. 76%, respectively); Cm/Prq was associated with similar adverse events (P = .57), steroid use (P = .74), and rashes (P = .78). This trial confirms that Cm/Prq is a reasonable alternative therapy for mild and moderately severe PCP.

Although drug-induced rash is frequent in human immunodeficiency virus (HIV)-infected patients, rash due to pyrimethamine has not been described previously. In a randomized, double-blind, placebo-controlled study of pyrimethamine as primary prophylaxis for toxoplasmic encephalitis, the incidence of rash (per hundred patient-years) was 8.1 in the pyrimethamine group versus 1.5 in the placebo group (P < .0002). The 1-year incidence of toxoplasmic encephalitis after occurrence of rash was 37%, as compared with 9.6% in the pyrimethamine group without rash, with a 3.7 times higher risk for patients with pyrimethamine-induced rash (P = .001); the incidence was 13% in the placebo group. At the time of toxoplasmic encephalitis, pyrimethamine was successfully readministered to 80% of patients who discontinued it because of rash. Thus, pyrimethamine, when used for prophylaxis, does induce rash in HIV-infected patients. These patients are at higher risk for toxoplasmic encephalitis and should be carefully monitored for it.

E. coli O157:H7 is one of many E. coli organisms that contain genes encoding one or more toxins similar in structure and function to Shiga toxin. E. coli O157:H7 is the most frequently isolated diarrheagenic type of E. coli isolated in North America today; this pathogen can cause serious, even fatal disease. Syndromes caused by E. coli O157:H7 include diarrhea, hemorrhagic colitis, and HUS. Poorly cooked ground beef has been the most frequently implicated vehicle of transmission, but additional vehicles are being identified. Treatment consists of rehydration during hemorrhagic colitis and support of the patient during the multiple systemic complications of HUS. A policy of routine screening for E. coli O157:H7 in clinical microbiology laboratories, without reliance on the physician to request that this organism be sought or the technician to notice blood in the stool, is the most effective way to find cases. Timely and accurate diagnosis can prevent secondary transmission, avert unnecessary and possibly dangerous procedures and/or therapies, and detect continuing outbreaks. SLTEC strains other than E. coli O157:H7 may cause diseases similar to or less severe than those caused by E. coli O157:H7. At present, however, screening for such pathogens in clinical laboratories is too labor-intensive to be practical. Education and legislation should promote safe food-preparation and food-handling practices. Research should be directed at reducing the carriage of E. coli O157:H7 at its bovine source, minimizing the microbial content of food and water, and averting systemic microangiopathic hemolytic anemia after infection with this pathogen.

We conducted a randomized, open-label trial in 42 French hospitals to compare the clinical and bacteriologic efficacy of combination therapy with clarithromycin/clofazimine (Clm/Clof) with that of combination therapy with clarithromycin/rifabutin/ethambutol (Clm/Rib/Eth) as treatment for Mycobacterium avium bacteremia. One hundred forty-four human immunodeficiency virus-seropositive patients older than 18 years of age who had CD4 lymphocyte counts of <100/mm3 and a blood culture positive for M. avium were enrolled in the study. The main measures of outcome were blood cultures, abatement of clinical symptoms (fever), and survival. Treatment success (defined as patient living, either no fever or a reduction of > or = 1 degrees C in initial body temperature, and a blood culture negative for M. avium) was similar in both treatment groups at months 2 and 6. However, following initial resolution of infection, relapse of M. avium bacteremia occurred in more patients in the Clm/Clof group than in the Clm/Rib/Eth group (22 vs. six, respectively; P < .001); these relapses were accompanied by emergence of strains resistant to clarithromycin in 21 and two patients, respectively. In conclusion, combination therapy with Clm/Rib/Eth prevented relapse of mycobacterial disease and, compared with combination therapy with Clm/Clof, was associated with a significant decrease in the emergence of resistant M. avium strains in HIV-infected patients treated for at least 28 weeks.

In this AIDS commentary, Dr. Wilfert has reviewed the American experience with vertical transmission of human immunodeficiency virus type 1 (HIV-1) since the closing of the 076 trial performed by the AIDS Clinical Trials Group in February 1994. The news generally is good; the rate of transmission from mother to child in nonstudy situations has been reduced when counseling and therapy are offered to pregnant women. As Dr. Wilfert emphasizes, the mechanism of the beneficial effect remains to be elucidated. More important, the resources required to insure that women have access to counseling and care need to be secured. In addition to these issues discussed by Dr. Wilfert, questions that need to be addressed include the efficacy and safety of more-potent antiretroviral agents or combinations in further reducing the risk of transmission, the optimal intervention for women who become pregnant while receiving antiretroviral therapy, the optimal postpartum management for women, and the most-effective treatment strategy for children born to infected women. The newborn child who is infected in spite of treatment of the mother potentially could receive great benefit from aggressive therapy designed to reduce the rate of viral replication and the selection of drug-resistant HIV-1. Finally, inexpensive and user-friendly methods of reducing the rate of vertical transmission in developing countries are urgently needed. Progress in reducing the prevalence of pediatric HIV-1 infection transmitted by mothers, the most common source of this infection in children, has been made, but further research and effort to insure access to care and answers to unsolved problems are necessary.

Efavirenz (EFV) is a highly active antiretroviral drug, use of which is associated with frequent (although transient) neurosensorial adverse reactions. Whether the use of EFV is associated with the risk of depression or suicide remains controversial. ALIZE-ANRS (Agence Nationale de Recherches sur le SIDA et les Hepatites Virales) 099 was a 48-week randomized trial involving virologically suppressed, human immunodeficiency virus (HIV)-infected patients that compared the maintenance of a treatment regimen that contained protease inhibitors (177 subjects) with a switch to a once-daily combination of EFV, didanosine, and emtricitabine (178 subjects). We used the trial's adverse events reporting system and a self-administered Center for Epidemiologic Studies-Depression Scale questionnaire to assess depressive disorders. Determinants were studied using a multivariate proportional hazards model adjusted for antiretroviral treatment, sex, age, HIV risk factor, history of depression, hepatic disorder, alcohol abuse, and HIV-related or non-HIV-related events. Thirty cases of depressive disorder (26 cases of depression and 4 suicide attempts) occurred during treatment in 27 patients (12 patients [7%] and 15 patients [8%] in the protease inhibitor-based and EFV-based treatment arms, respectively; P = .56). In the proportional hazards model, only age (hazard ratio, 1.6 per 10 years younger; 95% confidence interval, 1.0-2.6) and a history of depressive disorder (hazard ratio, 5.0; 95% confidence interval, 2.1-12.0) were associated with a risk of depressive disorders. The proportion of depressive patients (24%), as determined on the basis of the Center for Epidemiologic Studies-Depression Scale data, was stable during the follow-up period, without difference between treatment groups. Patients with a history of depressive disorder were more frequently depressed (53%) than were those without such history (22%; P = .03). The frequency of depressive disorders was high in this population, but the disorders were not related to EFV treatment. Younger age and a history of depression are important determinants for depression and should be considered for early detection and case management.

Gliadel wafers (1,3-bis [2-chloroethyl]-1-nitrosourea; Guilford Pharmaceuticals) are approved for the treatment of malignant gliomas; however, the incidence of and risk factors associated with infection with respect to this new technology are unknown. We identified 32 patients who received Gliadel wafers from December 1996 through October 1999. Nine patients (28%) developed ∼1 surgical site infection (SSI), which included 4 cases of brain abscess. All 3 patients who received vancomycin for surgical prophylaxis developed an SSI. In addition, multivariable analysis revealed an association between infection and a clinical diagnosis of depression. The National Nosocomial Infection Surveillance Surgical Site Index did not predict the onset of SSI after Gliadel wafer implantation. Patients who received a Gliadel wafer had a higher incidence of infection than previously has been reported, and additional studies are required to better quantify this risk and describe the epidemiology of such infections.

(1,3)-β-D-glucan (BG) is a biomarker for invasive candidiasis (IC). The usefulness of BG level as a prognostic marker of treatment outcome is not well characterized. Two hundred fifty-seven patients with proven IC were enrolled in an anidulafungin study. Clinical and microbiological responses at the end of therapy were evaluated. Serial serum BG was measured. Correlation of initial and final BG levels with overall outcome was assessed in each patient. Two hundred three patients had at least 2 BG levels and outcomes assessed. The majority of IC was caused by non-Candida albicans (53%) and found in the blood (84%). Overall, treatment success was 85%. In successfully treated patients, the mean ± SD initial and final BG were 573 ± 681 pg/mL and 499 ± 635 pg/mL (P = .03), respectively; while in treatment-failure patients, the levels were 1224 ± 1585 pg/mL and 1293 ± 1283 pg/mL (P = .29), respectively. A negative slope in BG levels correlated with a successful treatment outcome with a positive predictive value (PPV) of 90%, and a positive slope in BG levels correlated with treatment failure with a negative predictive value (NPV) of 90%. The cutoff value for initial BG <416 pg/mL has potential to predict treatment success with a PPV of 89%. A decrease in BG levels during therapy is associated with treatment success. An initial BG of <416 pg/mL has potential to predict successful treatment outcomes. Baseline and consecutive serum BG measurements may be useful as prognostic markers of treatment outcome in patients with IC receiving primarily echinocandin therapy.

To study the difference between the sexes with regard to chronic hepatitis B virus infection, we surveyed levels of serum hepatitis B e antigen (HBeAg) and alanine aminotransferase (ALT) among 10,431 asymptomatic Chinese carriers of hepatitis B surface antigen (HBsAg) in Taiwan. There were 7,095 men and 3,336 women in this study; ages ranged from 15 to 70 years. HBeAg was detected in 19.6% of HBsAg carriers. The prevalence of HBeAg decreased significantly with increasing age. HBeAg was detected in 17.7% of men and 23.6% of women. After correction for the confounding effect of age, it was found that the prevalence of HBeAg was significantly higher among women than among men. The level of serum ALT was abnormal in 20.8% of HBsAg carriers. Abnormal ALT levels were significantly more frequent among HBsAg carriers who tested positive for HBeAg (39.7%) than among those who did not (16.2%; P < .001). Among the HBeAg-positive carriers, 43.2% of men and 34.2% of women had abnormal ALT levels, and men were 1.45 times more likely to have abnormal ALT levels than women (P < .001). Among the carriers who were negative for HBeAg, 20.6% of men and only 6.0% of women had abnormal ALT levels, and men were 3.98 times more likely to have abnormal ALT levels than women (P < .001). Overall, 24.6% of men and only 12.6% of women had abnormal ALT levels, and men were 2.33 times more likely to have abnormal ALT levels than were women (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Phaeohyphomycosis refers to infections caused by darkly pigmented fungi. These fungi rarely cause life-threatening disease. We reviewed 101 cases of culture-proven primary central nervous system phaeohyphomycosis reported in the English-language literature from 1966 to 2002. The most frequently isolated species was Cladophialophora bantiana. The next most frequent isolate was Ramichloridium mackenziei, seen exclusively in patients from the Middle East. More than one-half of the cases occurred in patients with no known underlying immunodeficiency. Mortality rates were high regardless of immune status. Therapy is not standardized, although the combination of amphotericin B, flucytosine, and itraconazole may improve survival rates. Newer azoles, such as voriconazole, also have a broad spectrum of activity against these fungi, although clinical experience is limited. Complete excision of brain lesions may provide better results than simple aspiration. An aggressive medical and surgical approach is warranted in treating these infections to optimize outcomes.

Multidrug-resistant Salmonella enterica serotype Typhimurium Definitive Type 104 (DT104) emerged in the 1990s and is associated with greater clinical severity than pansusceptible S. Typhimurium. Although infection with DT104 is common in the United States, it is rarely associated with outbreaks. From October to December 2003, a cluster of DT104 infections with indistinguishable pulsed-field gel electrophoresis patterns was identified in the northeastern United States. A case-control study that assessed exposures compared case patients to age- and geography-matched control subjects. Information on consumer purchasing and grocery store suppliers was used to trace the implicated food to its source. We identified 58 case patients in 9 states by pulsed-field gel electrophoresis. Representative isolates were phage type DT104 and were resistant to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline (R-type ACSSuT). Of 27 patients interviewed for the case-control study, 41% were hospitalized (median duration of hospitalization, 4 days). Compared with 71 healthy control subjects, case patients had more medical comorbidities (matched odds ratio, 4.3; 95% confidence interval, 1.5-12.7). Illness was associated with consuming store-bought ground beef prepared as hamburgers at home (matched odds ratio, 5.3; 95% confidence interval, 1.9-15.3) and with eating raw ground beef (P< or =.001). Seven case patients (27%), but no control subjects, ate raw ground beef. Product traceback linked cases to a single large ground beef manufacturer previously implicated in a multistate outbreak of highly drug-resistant Salmonella enterica Newport infections in 2002. This first multistate outbreak of highly drug-resistant S. Typhimurium DT104 infection associated with ground beef highlights the need for enhanced animal health surveillance and infection control, prudent use of antimicrobials for animals, improved pathogen reduction during processing, and better product tracking and consumer education.

Cases of nontuberculous mycobacterial lymphadenitis were analyzed in a prospective study spanning 32 years, from 1958 to 1990. The results are based on personal observations and long-term follow-up. There were 105 cases, all of which occurred in children aged 9 1/2 months to 12 years (median age, 2.92 years). The patients were predominantly female, and the cases occurred more often in the winter and spring. The cervical or facial nodes were involved in 96 cases. An abrupt change in the predominant etiologic agent (from Mycobacterium scrofulaceum to Mycobacterium avium complex) was noted in the 1970s. Positive tuberculin skin tests were the rule, and reactivity was long lasting. Complications included a prolonged initial phase of infection (n = 6) and recurrences 3 1/2 months to 7 years later (n = 5). Resection during the early stage of infection produced the most satisfactory healing.

The etiologic and clinical features of cholecystitis in infection due to human immunodeficiency virus (HIV) were studied retrospectively. The charts and histopathologic specimens of 136 HIV-infected patients who underwent cholecystectomy between February 1987 and May 1993 at a large tertiary care center were reviewed. Opportunistic pathogens infecting the 107 patients with AIDS included microsporidia (eight cases—Enterocytozoon bieneusi in six and Septata intestinalis in two); cytomegalovirus alone (six cases); Cryptosporidium alone (eight cases); cytomegalovirus plus Cryptosporidium (15 cases); and Pneumocystis carinii and Isospora belli (one case each). In addition, histopathologic changes characteristic of Kaposi's sarcoma were seen in one case. Thirty-eight patients with AIDS had acalculous cholecystitis for which no etiologic agent was found. Twenty-eight AIDS patients had cholelithiasis, six with coexistent opportunistic gallbladder infection. In the 107 AIDS patients, no specific symptom was found to be predictive of opportunistic infection of the gallbladder, but such infection was significantly associated with an abnormal abdominal ultrasound (P = .017) and with nonvisualization of the gallbladder by radionucleotide biliary scan (P < .001).

Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality among transplant recipients. For the purpose of developing consistent reporting of CMV in clinical trials, definitions of CMV infection and disease were developed and published. This study seeks to update the definitions of CMV on the basis of recent developments in diagnostic techniques, as well as to add to these definitions the concept of indirect effects caused by CMV.

We report the clinical and microbiological characteristics of 11 cases of Aeromonas hydrophila infection of skin and soft tissue, and we review the English-language literature on such infections. Of our 11 patients, seven (64%) presented to the hospital between the months of May and September (inclusive). Three patients (27%) had an underlying systemic illness, and two (18%) had nosocomially acquired infection. The nine patients with community-acquired infection had all experienced antecedent trauma, and seven (78%) of these nine reported recent exposure to freshwater. All patients had clinical evidence of soft-tissue inflammation, and nine (82%) had fever. Four wounds were characterized by a foul odor. The infection was polymicrobial in nine cases (82%). Treatment included the administration of antibiotics in nine instances, but empirical antimicrobial therapy provided coverage against Aeromonas in only two cases. Ten patients required surgical management of their wounds. Posttraumatic wound infections with a history of freshwater exposure should alert the clinician to the possible presence of A. hydrophila. Prompt surgical evaluation of wounds in combination with appropriate antibiotic therapy is recommended for the management of these infections.

The incidence of invasive Haemophilus influenzae infection decreased dramatically since the introduction of the H. influenzae serotype b (Hib) conjugate vaccine. H. influenzae invasive disease continues to occur and cause significant morbidity and mortality in children aged <5 years. We aimed to report the epidemiology and serotypes of invasive H. influenzae disease in children from Utah in the post-Hib vaccine era. We identified all cases of invasive H. influenzae disease, defined as H. influenzae isolated from a sterile site, during the period 1998-2008 among children aged <18 years who were living in Utah. We identified 91 cases of invasive H. influenzae disease in children. Children aged <5 years accounted for 78 cases (86%). H. influenzae serotype a (Hia) was the most common serotype (22 cases), representing 28% of all cases of invasive disease among children aged <5 years. The majority (15 cases [93%]) of Hib disease cases occurred among children aged <5 years and accounted for 18% of all cases of H. influenzae invasive disease in this age group. The mean incidence of Hia disease increased from 0.8 cases per 100,000 child-years in 1998 to 2.6 cases per 100,000 child-years in 2008. The incidence of Hib disease among children aged <5 years remained steady at 0.5 cases per 100,000 child-years. Bacteremia accounted for 61% of all cases of invasive disease. One-half (13 of 26) of cases of H. influenzae meningitis were due to Hia. H. influenzae continues to cause invasive disease in Utah children. Hia is the primary cause of the overall increased incidence of invasive H. influenzae disease and leads to disease similar to Hib. Isolated cases of Hib disease demonstrate a continued reservoir. The success of the Hib conjugate vaccine may therefore be vulnerable to vaccine shortages and refusal of vaccination.

We report the clinical and biological course of infection with human immunodeficiency virus (HIV) type 1 in 11 liver transplant recipients who acquired this infection between 1985 and 1987. Eight patients were infected by blood or blood products from graft-related transfusions and one by the graft itself; the remaining two patients were infected after transplantation and had independent risk factors. All patients received a triple-drug immunosuppressive regimen including cyclosporine. The mean duration of follow-up after liver transplantation was 52 months (standard error, ±32 months). Chronic graft rejection was documented in four cases. The cumulative incidences of HIV-related complications and HIV-related deaths were 82% and 27%, respectively. Three patients died rapidly of HIV disease. The survival rate 7 years after transplantation was 36% among the 11 HIV-infected patients, whereas it was ∼70% among HIV-negative liver transplant recipients during the same period. The course of HIV infection in the four survivors did not appear to differ from that in other patients infected by blood transfusion.

We studied the clinical resistance to acyclovir of infections with varicella-zoster viruses (VZV) in patients with acquired immunodeficiency syndrome, and we correlated it to virologic analyses. Eleven patients with VZV infections (treated with acyclovir, 30 mg/kg/day, given intravenously, or 4 g/day, given orally) were included in the study because of the failure of 10 days of acyclovir therapy. Susceptibility of VZV isolates to acyclovir was tested using a plaque reduction assay to determine the 50% inhibitory concentration (IC50) of acyclovir and the SI50 (IC50 of the patient isolate/IC50 of the reference strain) to acyclovir. The thymidine kinase (TK) gene, which supports the resistance, was sequenced on amplified products. Only 3 patients had a significant increase in the IC50, as compared with the IC50 of the reference strain (SI50 of ⩾4), and a mutation in the TK gene. For the other 8 patients, the clinical resistance was not confirmed by the virologic results: the SI50 was <4, and no mutation was detected in the TK gene. Because no acyclovir-resistant strain appeared during a shorter period of time, we suggest an increase in the duration of the treatment to 21 days before acyclovir resistance is suspected.

We describe the features of 13 cases of Pseudomonas aeruginosa folliculitis (eight of which occurred sporadically and five of which resulted from two family outbreaks) that developed subsequent to the use of commercial synthetic sponges for bathing. On the basis of O serogrouping and pyocin typing and subtyping, the strains recovered from the skin lesions were found to be identical to those isolated from household shower water and sponges. P. aeruginosa folliculitis is commonly caused by the serogroup O:11; The serogroups described in this study are rare causative agents of this type of skin infection. We believe that this is the first report of P. aeruginosa folliculitis due to serogroups O:3 and O:16.

A 9-month course of isoniazid monotherapy is currently recommended for the treatment of latent tuberculosis infection (LTBI) and has been shown to be effective in both children and adults. Reduced compliance with this regimen has forced physicians to explore shorter regimens. The aim of this study was to compare 3- and 4-month combination regimens of isoniazid plus rifampin with a 9-month regimen of isoniazid monotherapy for the treatment of LTBI in children. This prospective, randomized, controlled study was conducted over an 11-year period (1995-2005). In period 1 (1995-1998), 232 patients received isoniazid therapy for 9 months (group A), and 238 patients received isoniazid and rifampin for 4 months (group B). In period 2 (1999-2002), 236 patients were treated with isoniazid and rifampin for 4 months (group C), and 220 patients received the same regimen for 3 months (group D). All patients were observed for > or = 3 years. Overall compliance with treatment was good, but patients who received isoniazid monotherapy were less compliant than were those who received short-course combination therapy (P=.011, for group A vs. group B; P=.510, for group C vs. group D). No patient in any group developed clinical disease during the follow-up period. New radiographic findings suggestive of possible active disease were more common in patients who received isoniazid monotherapy (24%) than in those treated with shorter regimens (11.8%, 13.6%, and 11% for groups B, C, and D, respectively; P=.001 for group A vs. group B; P=.418 for group C vs. group D). Serious drug-related adverse effects were not detected. Short-course treatment with isoniazid and rifampin for 3-4 months is safe and seems to be superior to a 9-month course of isoniazid monotherapy.

The etiologic and clinical features of cholecystitis in infection due to human immunodeficiency virus (HIV) were studied retrospectively. The charts and histopathologic specimens of 136 HIV-infected patients who underwent cholecystectomy between February 1987 and May 1993 at a large tertiary care center were reviewed. Opportunistic pathogens infecting the 107 patients with AIDS included microsporidia (eight cases—Enterocytozoon bieneusi in six and Septata intestinalis in two); cytomegalovirus alone (six cases); Cryptosporidium alone (eight cases); cytomegalovirus plus Cryptosporidium (15 cases); and Pneumocystis carinii and Isospora belli (one case each). In addition, histopathologic changes characteristic of Kaposi's sarcoma were seen in one case. Thirty-eight patients with AIDS had acalculous cholecystitis for which no etiologic agent was found. Twenty-eight AIDS patients had cholelithiasis, six with coexistent opportunistic gallbladder infection. In the 107 AIDS patients, no specific symptom was found to be predictive of opportunistic infection of the gallbladder, but such infection was significantly associated with an abnormal abdominal ultrasound (P = .017) and with nonvisualization of the gallbladder by radionucleotide biliary scan (P < .001).

Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality among transplant recipients. For the purpose of developing consistent reporting of CMV in clinical trials, definitions of CMV infection and disease were developed and published. This study seeks to update the definitions of CMV on the basis of recent developments in diagnostic techniques, as well as to add to these definitions the concept of indirect effects caused by CMV.

The incidence of invasive Haemophilus influenzae infection decreased dramatically since the introduction of the H. influenzae serotype b (Hib) conjugate vaccine. H. influenzae invasive disease continues to occur and cause significant morbidity and mortality in children aged <5 years. We aimed to report the epidemiology and serotypes of invasive H. influenzae disease in children from Utah in the post-Hib vaccine era. We identified all cases of invasive H. influenzae disease, defined as H. influenzae isolated from a sterile site, during the period 1998-2008 among children aged <18 years who were living in Utah. We identified 91 cases of invasive H. influenzae disease in children. Children aged <5 years accounted for 78 cases (86%). H. influenzae serotype a (Hia) was the most common serotype (22 cases), representing 28% of all cases of invasive disease among children aged <5 years. The majority (15 cases [93%]) of Hib disease cases occurred among children aged <5 years and accounted for 18% of all cases of H. influenzae invasive disease in this age group. The mean incidence of Hia disease increased from 0.8 cases per 100,000 child-years in 1998 to 2.6 cases per 100,000 child-years in 2008. The incidence of Hib disease among children aged <5 years remained steady at 0.5 cases per 100,000 child-years. Bacteremia accounted for 61% of all cases of invasive disease. One-half (13 of 26) of cases of H. influenzae meningitis were due to Hia. H. influenzae continues to cause invasive disease in Utah children. Hia is the primary cause of the overall increased incidence of invasive H. influenzae disease and leads to disease similar to Hib. Isolated cases of Hib disease demonstrate a continued reservoir. The success of the Hib conjugate vaccine may therefore be vulnerable to vaccine shortages and refusal of vaccination.

We describe the features of 13 cases of Pseudomonas aeruginosa folliculitis (eight of which occurred sporadically and five of which resulted from two family outbreaks) that developed subsequent to the use of commercial synthetic sponges for bathing. On the basis of O serogrouping and pyocin typing and subtyping, the strains recovered from the skin lesions were found to be identical to those isolated from household shower water and sponges. P. aeruginosa folliculitis is commonly caused by the serogroup O:11; The serogroups described in this study are rare causative agents of this type of skin infection. We believe that this is the first report of P. aeruginosa folliculitis due to serogroups O:3 and O:16.

A 9-month course of isoniazid monotherapy is currently recommended for the treatment of latent tuberculosis infection (LTBI) and has been shown to be effective in both children and adults. Reduced compliance with this regimen has forced physicians to explore shorter regimens. The aim of this study was to compare 3- and 4-month combination regimens of isoniazid plus rifampin with a 9-month regimen of isoniazid monotherapy for the treatment of LTBI in children. This prospective, randomized, controlled study was conducted over an 11-year period (1995-2005). In period 1 (1995-1998), 232 patients received isoniazid therapy for 9 months (group A), and 238 patients received isoniazid and rifampin for 4 months (group B). In period 2 (1999-2002), 236 patients were treated with isoniazid and rifampin for 4 months (group C), and 220 patients received the same regimen for 3 months (group D). All patients were observed for > or = 3 years. Overall compliance with treatment was good, but patients who received isoniazid monotherapy were less compliant than were those who received short-course combination therapy (P=.011, for group A vs. group B; P=.510, for group C vs. group D). No patient in any group developed clinical disease during the follow-up period. New radiographic findings suggestive of possible active disease were more common in patients who received isoniazid monotherapy (24%) than in those treated with shorter regimens (11.8%, 13.6%, and 11% for groups B, C, and D, respectively; P=.001 for group A vs. group B; P=.418 for group C vs. group D). Serious drug-related adverse effects were not detected. Short-course treatment with isoniazid and rifampin for 3-4 months is safe and seems to be superior to a 9-month course of isoniazid monotherapy.

We report the clinical and biological course of infection with human immunodeficiency virus (HIV) type 1 in 11 liver transplant recipients who acquired this infection between 1985 and 1987. Eight patients were infected by blood or blood products from graft-related transfusions and one by the graft itself; the remaining two patients were infected after transplantation and had independent risk factors. All patients received a triple-drug immunosuppressive regimen including cyclosporine. The mean duration of follow-up after liver transplantation was 52 months (standard error, ±32 months). Chronic graft rejection was documented in four cases. The cumulative incidences of HIV-related complications and HIV-related deaths were 82% and 27%, respectively. Three patients died rapidly of HIV disease. The survival rate 7 years after transplantation was 36% among the 11 HIV-infected patients, whereas it was ∼70% among HIV-negative liver transplant recipients during the same period. The course of HIV infection in the four survivors did not appear to differ from that in other patients infected by blood transfusion.

We studied the clinical resistance to acyclovir of infections with varicella-zoster viruses (VZV) in patients with acquired immunodeficiency syndrome, and we correlated it to virologic analyses. Eleven patients with VZV infections (treated with acyclovir, 30 mg/kg/day, given intravenously, or 4 g/day, given orally) were included in the study because of the failure of 10 days of acyclovir therapy. Susceptibility of VZV isolates to acyclovir was tested using a plaque reduction assay to determine the 50% inhibitory concentration (IC50) of acyclovir and the SI50 (IC50 of the patient isolate/IC50 of the reference strain) to acyclovir. The thymidine kinase (TK) gene, which supports the resistance, was sequenced on amplified products. Only 3 patients had a significant increase in the IC50, as compared with the IC50 of the reference strain (SI50 of ⩾4), and a mutation in the TK gene. For the other 8 patients, the clinical resistance was not confirmed by the virologic results: the SI50 was <4, and no mutation was detected in the TK gene. Because no acyclovir-resistant strain appeared during a shorter period of time, we suggest an increase in the duration of the treatment to 21 days before acyclovir resistance is suspected.

We report the clinical and microbiological characteristics of 11 cases of Aeromonas hydrophila infection of skin and soft tissue, and we review the English-language literature on such infections. Of our 11 patients, seven (64%) presented to the hospital between the months of May and September (inclusive). Three patients (27%) had an underlying systemic illness, and two (18%) had nosocomially acquired infection. The nine patients with community-acquired infection had all experienced antecedent trauma, and seven (78%) of these nine reported recent exposure to freshwater. All patients had clinical evidence of soft-tissue inflammation, and nine (82%) had fever. Four wounds were characterized by a foul odor. The infection was polymicrobial in nine cases (82%). Treatment included the administration of antibiotics in nine instances, but empirical antimicrobial therapy provided coverage against Aeromonas in only two cases. Ten patients required surgical management of their wounds. Posttraumatic wound infections with a history of freshwater exposure should alert the clinician to the possible presence of A. hydrophila. Prompt surgical evaluation of wounds in combination with appropriate antibiotic therapy is recommended for the management of these infections.

Staphylococcus lugdunensis is a recently described coagulase-negative staphylococcus that has been associated with human infections, including nine reported cases of infective endocarditis. The present study describes 11 other cases of infective endocarditis caused by this organism. The infection occurred in patients whose mean age was 61 years and was community-acquired in most cases. A preexisting cardiac abnormality was present in eight patients. Three of the 11 infections involved prosthetic valves. Ten strains were susceptible to penicillin. The destructive course of the infection, the need for valve replacement, and the high mortality suggest that S. lugdunensis causes a virulent form of endocarditis.

Indium-111-labeled human nonspecific immunoglobulin G (111In-IgG) is a newly developed radiopharmaceutical for imaging infectious and inflammatory foci. This article presents an overview of the literature concerning In-IgG scintigraphy. The current theory about the mechanism of accumulation suggests that 111In-IgG accumulates in lesions as a result of enhanced vascular permeability and subsequent entrapment of the radiolabeled protein. Human studies show excellent results in imaging bone and joint, abdominal, and intravascular infection. Of special interest is the ability to depict infectious foci in granulocytopenic patients. The value of 111In-IgG scintigraphy for detection of infection is compared with that of gallium-67, labeled-leukocyte, and technetium-99m (99mTc) nanocolloid scintigraphy. The significance of differences between 111In-IgG scintigraphy and two other new scintigraphic techniques, 99mTc-labeled IgG and 99mTc-labeled murine monoclonal anti-granulocyte antibody BW 250/183, are discussed.

Temporal trends in the incidence of opportunistic diseases (ODs) related to acquired immunodeficiency syndrome (AIDS) were studied during 1989–1997 in 1115 outpatients infected with human immunodeficiency virus (331 of whom had AIDS) in a hospital in Madrid, Spain. We analyzed the effect of adherence to antiretroviral therapy and Pneumocystis carinii pneumonia (PCP) prophylaxis on the incidence of OD. Diseases that showed a significant decreasing trend were esophageal candidiasis, pulmonary and extrapulmonary tuberculosis, and cerebral toxoplasmosis. Patients who adhered to antiretroviral therapy had a smaller risk of OD. Patients who adhered to PCP prophylaxis had a reduced risk of cerebral toxoplasmosis and PCP. A reduction in the incidence of AIDS-related ODs was observed, mainly in patients who underwent prophylaxis. Adherence to antiretroviral treatment and PCP prophylaxis was associated with a reduction in the risk of disease.

Streptococcus pneumoniae is a commensal colonizer of the human nasopharynx (NP) that causes disease after evasion of host defenses and dissemination. Pneumococcal strains expressing the newly identified serotype 11E arise from antigenically similar 11A progenitors by genetic inactivation of the O-acetyltransferase gene wcjE. Each 11E strain contains a distinct mutation to wcjE, suggesting that 11E strains are not transmitted among hosts despite their recovery from multiple patients with pneumococcal disease. We investigated whether the presumed lack of transmission of serotype 11E is consistent with its inability to survive in the NP. More than 400 pneumococcal carriage, middle ear, conjunctiva, and blood isolates, serotyped as 11A by Quellung reaction, were reexamined for reactivity to 11A- and 11E-specific antibodies. We confirmed serotyping of isolates with sequencing of wcjE alleles. Serotype 11E strains were statistically more likely to occur among blood (4 of 15), conjunctiva (1 of 14), or middle ear (2 of 21) isolates than among carriage isolates (2 of 355). All 11E isolates contained unique mutations that putatively decrease wcjE expression. The lack of a circulating 11E clone and the increased occurrence of 11E strains among disease isolates supports the idea that serotype 11E independently arises during infection after initial colonization with a serotype 11A progenitor. Factors encountered in the NP likely contribute to relative rarity of 11E among carriage isolates, whereas selective pressures in deeper tissues possibly promote 11E emergence. These findings illustrate a novel model of microevolution that transpires during the span of a single encounter with serotype 11A, highlighting the adaptability of bacterial pathogens within hosts.

The relationship between the use of tumor necrosis factor antagonists and onset of granulomatous infection was examined using data collected through the Adverse Event Reporting System of the US Food and Drug Administration for January 1998–September 2002. Granulomatous infections were reported at rates of ∼239 per 100,000 patients who received infliximab and ∼74 per 100,000 patients who received etanercept (P < .001). Tuberculosis was the most frequently reported disease, occurring in ∼144 and ∼35 per 100,000 infliximab-treated and etanercept-treated patients, respectively (P < .001). Candidiasis, coccidioidomycosis, histoplasmosis, listeriosis, nocardiosis, and infections due to nontuberculous mycobacteria were reported with significantly greater frequency among infliximab-treated patients. Seventy-two percent of these infection occurred ⩽90 days after starting infliximab treatment, and 28% occurred after starting etanercept treatment (P < .001). These data indicate a risk of granulomatous infection that was 3.25-fold greater among patients who received infliximab than among those who received etanercept. The clustering of reports shortly after initiation of treatment with infliximab is consistent with reactivation of latent infection.

Although Acinetobacter baumannii (formerly Acinetobacter calcoaceticus var. anitratus) is known to be an important nosocomial pathogen, the clinical impact of other Acinetobacter species is not fully understood. Acinetobacter johnsonii (formerly a subset of A. calcoaceticus var. lwoffii) is considered a commensal on human skin, and infections due to this organism have not been reported previously. During a study period of 18 months, however, 13 patients at 6 hospitals developed catheter-related bloodstream infections caused by A. johnsonii. All patients had an indwelling peripheral or central venous catheter, and 11 patients were receiving a continuous intravenous infusion of heparin via the offending catheter. The clinical course of A. johnsonii bacteremia was usually benign. Infections responded readily to removal of the catheter, with or without administration of appropriate antibiotics. No insertion-site infections were documented. Thus A. johnsonii must be regarded as an organism that can cause rare cases of bloodstream infection in immunocompetent patients.