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Purpose: To report the successful treatment of 3 cases of recalcitrant fungal keratitis (FK) with high-dose oral posaconazole., Methods: This is a series of 3 patients from a single academic center with a culture-positive FK who were treated with oral posaconazole after failing to respond to conventional treatments., Results: All 3 patients had a history of contact lens wear. Two of the 3 cases were culture positive for Fusarium and the other for Paecilomyces . The infections of all 3 failed to respond to conventional antifungal therapies including varying combinations of topical, systemic, and intraocular antifungal therapies. All 3 cases rapidly responded to high-dose oral posaconazole ranging from 500 to 600 mg once daily. In 1 case, multiple courses of high-dose therapy were required to treat delayed recurrences of a latent infection. There were no significant adverse effects with the elevated dose, and treatment was administered with the guidance of an infectious disease specialist., Conclusions: In cases of recalcitrant FK failing to respond to conventional therapies, high-dose posaconazole, in the delayed-release tablet formulation, can be an effective treatment option., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Clostridioides difficile infection (CDI) causes significant morbidity and mortality; however, the diagnosis of CDI remains controversial. The primary aim of our study was to evaluate the association of polymerase chain reaction (PCR) cycle threshold (Ct) values with CDI disease severity, recurrence, and mortality among adult patients with CDI., Design: Retrospective cohort study., Setting: Single tertiary-care hospital., Patients: Adult patients diagnosed with hospital-onset, healthcare facility-associated CDI from June 2014 to September 2015., Methods: We performed a retrospective chart review of included patients. Univariate and multivariable logistic regression methods were used to evaluate the association between Ct values and CDI severity, 8-week recurrence, and 30-day mortality., Results: Among 318 included patients, 51% were male and the mean age was 62 years; ~32% of the patients developed severe CDI and 11% developed severe-complicated CDI. The 30-day all-cause mortality rate was 11% and the 8-week recurrence rate was 9.5%. The overall mean Ct value was 32.9 (range, 23-40). Multivariable analyses showed that lower values of PCR Ct were associated with increased odds of 30-day morality (odds ratio [OR] 0.83; 95% confidence interval [CI], 0.72-0.96) but were not independently associated with CDI severity (OR, 0.99; 95% CI, 0.90-1.09) or recurrence (OR, 0.88; 95% CI, 0.77-1.00)., Conclusions: Our findings suggest that PCR Ct values at the time of diagnosis may have a limited predictive value and utility in clinical decision making for inpatients with CDI. Larger, prospective studies across different patient populations are needed to confirm our findings.

Purpose of Review: The patient who presents with an acute spinal cord syndrome with weakness/paralysis of the limbs presents a diagnostic. Two important syndromes are acute transverse myelitis (ATM) and acute flaccid paralysis (AFP). Both can be caused by a number of infectious and noninfectious causes. Since 2014 there have been outbreaks of acute flaccid myelitis (a subgroup of AFP) in the United States, with a national surveillance program underway. In addition, there have been increasing reports of ATM from new and emerging pathogens, and opportunistic infections in immunocompromised hosts., Recent Findings: Infectious causes of ATM or AFP need to be ruled out first. There may be important clues to an infectious cause from epidemiologic risk factors, immune status, international travel, MRI, and laboratory findings. We summarize key features for the more common pathogens in this review. Advances in laboratory testing have improved the diagnostic yield from cerebrospinal fluid, including real-time polymerase chain reaction, metagenomic next-generation sequencing, and advanced antibody detection techniques. These tests still have limitations and require clinical correlation., Summary: We present a syndromic approach to infectious myelopathies, focusing on clinical patterns that help narrow the diagnostic possibilities.

Infectious diseases are a significant cause of morbidity and mortality in immunosuppressed patients, including those with connective tissue diseases. Both disease and treatment contribute to a predisposition to infection in immunocompromised patients. Significant infection and morbidity occur in 25% to 50% of these patients with a median mortality of 5.2% due to common bacterial infections, such as pneumonia or bacteremia, and opportunistic fungal infections such as Pneumocystis. The lungs, skin, urinary tract, blood, and central nervous system are commonly affected. Pathogens such as Pneumocystis jirovecii, Histoplasma capsulatum, Aspergillus species, herpes zoster, JC virus, Nocardia asteroides, and Nocardia species are increasingly prevalent in immunocompromised patients. Improved recognition, diagnosis, and prevention of these infections are needed to enhance outcomes in these patients.

Objectives: To describe the influence of age on clinical features of histoplasmosis., Design: Retrospective single-center cohort study., Setting: Large tertiary care center., Participants: All individuals who met criteria for probable or proven histoplasmosis between 1998 and 2008., Measurements: Participants were divided into the following categories of histoplasmosis: acute pulmonary, chronic pulmonary, asymptomatic, disseminated, and other. Correcting for immune status, the influence of age at diagnosis on presentation, diagnosis, imaging, treatment, and all-cause mortality was evaluated., Results: In 347 participants with histoplasmosis, a number of characteristics were associated with age when evaluating participants according to diagnostic category. An age-associated increase in asymptomatic histoplasmosis was observed (P < .001). In symptomatic pulmonary histoplasmosis, older adults were less likely to present with chest pain (P < .001) and less likely to have hilar lymphadenopathy on imaging (P = .04). Lower rates of seropositivity with older age were seen in asymptomatic (P = .04) but not other forms of histoplasmosis. Cavitary disease was associated with older age in chronic pulmonary histoplasmosis (P = .05). Treatment did not change with age. All-cause mortality at 6 months was 4% and was associated with older age (P = .02)., Conclusion: Although most studied characteristics of histoplasmosis were similar, notable age-related differences were present. Chronic cavitary disease and asymptomatic histoplasmosis were more common with older age. In acute histoplasmosis, the lack of chest pain and hilar lymphadenopathy may hinder diagnosis in older adults., (© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.)

The utility of cytomegalovirus (CMV) viral load (VL) by quantitative hybrid capture assay (Q-HCA) was investigated in bronchoalveolar lavage (BAL) from lung transplant recipients and compared with BAL cultures and blood VL. Forty-three consecutive BAL samples from 27 lung transplant recipients were analyzed. All samples had shell vial (SV) cultures in addition to Q-HCA. Histopathology was done on all lung tissues, and immunohistochemistry (IHC) in those with positive CMV cultures. Fifteen (56%) lung transplant recipients had both positive BAL SV cultures and BAL VL. Five of 15 had CMV pneumonitis with a VL in BAL >500 000 copies/mL (mean: 1638 450). Ten patients without CMV pneumonitis had VL in BAL <500 000 copies/mL (mean 81 820, p = 0.002). High VL in BAL and blood invariably meant CMV pneumonitis, but 2 patients with CMV pneumonitis had high BAL VL but relatively low blood VL. Initial CMV seronegativity was associated with pneumonitis (4/5 vs. 1/10; p = 0.004) and higher BAL CMV VL (p = 0.03). High CMV BAL or blood VL did not correlate with acute rejection or development of bronchiolitis obliterans syndrome (BOS). High CMV VL in BAL in lung transplant recipients is strongly associated with CMV pneumonitis, and may be more predictive than peripheral blood viral load.

Objective: To determine the accuracy and cost-effectiveness of a polymerase chain reaction (PCR) for detecting nasal carriage of Staphylococcus aureus directly from clinical specimens. CROSS-SECTIONAL STUDY: This occurred in a tertiary-care hospital in Cleveland, Ohio, and included 239 consecutive patients who were scheduled for a cardiothoracic surgical procedure. Conventional cultures and a PCR for S. aureus from nasal swabs were used as measurements. COST-EFFECTIVENESS ANALYSIS: Data sources were market prices and Bureau of Labor Statistics. The time horizon was the maximum period for availability of culture results (3 days). Interventions included universal mupirocin therapy without testing; initial therapy, with termination if PCR negative (treat-PCR); initial therapy, with termination if culture negative (treat-culture); treat PCR-positive carriers (PCR-guided treatment); and treat culture-positive carriers (culture-guided treatment). The perspective was institutional and costs and the length of time to treatment were outcome measures., Results: Sixty-seven (28%) of the 239 swabs grew S. aureus. Rapid PCR was 97.0% sensitive and 97.1% specific for the detection of S. aureus. For populations with prevalences of nasal S. aureus carriage of up to 50%, the PCR assay had negative predictive values of greater than 97%. PCR-guided treatment had the lowest incremental cost-effectiveness ratio (1.93 dollars per additional day compared with the culture strategy). Among immediate treatment strategies, treat-PCR was most cost-effective. The universal therapy strategy cost 38.19 dollars more per additional day gained with carrier identification compared with the PCR strategy., Conclusion: Rapid real-time PCR is an accurate, rapid, and cost-effective method for identifying S. aureus carriers for preoperative intervention.

West Nile fever has now spread to much of the United States. This disease can be diagnosed using one of several laboratory tests, notably an immunoglobulin M enzyme-linked immunosorbent assay. It can cause devastating neurologic damage, including an unusual polio-like syndrome. Magnetic resonance imaging is an important imaging tool in such patients. Treatment is largely supportive, although antiviral agents are under investigation.

West Nile virus (WNV) is an emerging mosquito-transmitted encephalitis virus first recognized in North America in 1999. The pathologic manifestations of WNV infection have not been well defined. This study documents the clinicopathologic features, including autopsy findings, of 2 cases: an 81-year-old man who contracted WNV infection with meningoencephalitis and a polio-like paralysis and a hospitalized 74-year-old woman with meningoencephalitis who acquired WNV through transfusion. The pathologic findings in both cases were marked by perivascular and leptomeningeal chronic inflammation, microglial nodules, and neuronophagia, predominantly involving the temporal lobes and brainstem. These findings also were present in the spinal cord, especially the lumbar region, of the patient with polio-like paralysis. In both cases, most of the inflammatory infiltrate was composed of CD3+ T lymphocytes (a predominance of CD8+ over CD4+ T cells), CD68+ macrophages, and rare CD20+ B lymphocytes. These cases further define the clinical and pathologic spectrum of central nervous system disease in WNV infection.

A retrospective chart review of all patients seen at the Cleveland Clinic Foundation with infectious endogenous endophthalmitis between January 1982 and August 2000 revealed 34 affected eyes in 27 patients. During this time, the median incidence of endogenous endophthalmitis was 1.8 cases/year, and 48.1% of patients presented as outpatients. Twenty-six patients presented to an ophthalmologist, and the diagnosis was initially missed in almost half the cases. Eleven patients had an unremarkable physical exam except for eye findings. We found an equal incidence of bacterial and fungal endophthalmitis and a predominance of among the fungal etiologic agents. We did not, however, note a predominance of Gramnegative organisms seen mostly in reports from Asia. The microbiologic diagnosis was based on aqueous and vitreous cultures or positive eye histopathology stains in almost two-thirds of cases. The sensitivity of the Gram stain was poor, but its specificity and positive predictive value were excellent. The vitreous cultures obtained by vitrectomy instruments were more sensitive in making the diagnosis than the vitreous needle biopsy. Aside from blood cultures and eye specimen cultures, half the patients had an additional infectious focus, most frequently a urinary tract infection, whereas infectious endocarditis was seen in a small minority. Twelve patients had visual improvement with treatment with a final visual acuity better than 20/200 in 44% of the eyes. Good visual outcome was associated with visual acuity of 20/200 or better at diagnosis and with the absence of hypopyon.

We designed and tested a real-time LightCycler PCR assay for Histoplasma capsulatum that correctly identified the 34 H. capsulatum isolates in a battery of 107 fungal isolates tested and also detected H. capsulatum in clinical specimens from three patients that were culture positive for this organism.

The increasing prevalence of vancomycin-resistant enterococcal (VRE) infections has necessitated a search for drugs that are effective in treating these infections, and a need to determine whether currently available antimicrobials are effective. 75 consecutive clinical isolates of vancomycin-resistant Enterococcus faecium (VRE faecium) (40 blood and 35 urine isolates) isolated over 1 y at the Cleveland Clinic Foundation were tested for susceptibility to linezolid, quinupristin-dalfopristin, fosfomycin and nitrofurantoin using the Etest. The minimum inhibitory concentrations were read independently by 3 observers and compared, and a final reading was obtained by predetermined criteria. The proportion of isolates susceptible to linezolid, quinupristin-dalfopristin, fosfomycin and nitrofurantoin was 100%, 98.7%, 98.7% and 78.7%, respectively. No single isolate was resistant to more than 1 of the 4 drugs tested. Etest presented significant unexpected difficulties in testing for VRE faecium susceptibility to nitrofurantoin. Fosfomycin may be a useful alternative to linezolid and quinupristin-dalfopristin in the treatment of VRE infections in certain clinical situations, e.g. uncomplicated urinary tract infections. In addition, the use of fosfomycin could limit the use of newer agents, thus reducing the chance of development of further resistance in the enterococci.

Endogenous endophthalmitis due to Actinobacillus actinomycetemcomitans is an unusual disease with serious sequelae. Of the 4 cases published in the literature only 1 recovered useful vision after treatment. This study reports on 1 additional patient and expands on the previously described brief ophthalmology case report of another patient with marked visual impairment at presentation and good visual recovery after treatment. Of the 5 patients described, 4 had pre-existing heart abnormalities, 3 had permanent pacemakers and 2 had periodontal disease. Definite endocarditis by Duke criteria was present in 3 patients. Endocarditis should be ruled out in every patient with A. actinomycetemcomitans endophthalmitis, even in the absence of systemic complaints and prior penicillin prophylaxis. Eye specimen cultures should be incubated for 10 d. A thorough dental examination should be done in each patient and any periodontal disease should be promptly treated.

Background: Ganciclovir-resistant (GCV-R) cytomegalovirus (CMV) is now being reported with increasing frequency in solid organ transplant recipients., Objective: To describe the clinical characteristics and outcomes of all solid organ transplant patients with GCV-R CMV seen between 1990 and 2000 at a single center., Methods: Patients with clinically suspected GCV resistance had viral isolates subjected to phenotypic analysis by plaque reduction assay, and also genotypic analysis. Medical records of the 13 patients with GCV-R CMV were reviewed for demographic, microbiologic, clinical, and pathologic data., Results: Thirteen patients were identified, including 5 kidney, 1 heart, and 7 lung transplant recipients. All but one patient (92%) were CMV donor seropositive, recipient negative (D+/R-), and 11/13 (85%) had tissue-invasive CMV. CMV viremia was recurrent in 9/13 (69%); in 2 others, the first CMV episode was fatal. Overall, 9/13 (69%) of patients have died, all of CMV or its complications. Of the 10 who received foscarnet, only one survived. All patients had received GCV-based prophylactic regimens; 8/13 patients (62%) had received CMV hyperimmune globulin (CMVIG) as part of prophylaxis, 6/13 (46%) had received oral ganciclovir, and 5/13 (38%) had received intermittent (3 x/week) IV ganciclovir for prophylaxis., Conclusions: GCV-R CMV is associated with CMV D+/R- status, tissue-invasive disease, and high mortality even with foscarnet therapy. Exposure to less than fully therapeutic levels of GCV, in the form of oral or intermittent IV GCV, is common. The use of CMVIG in prophylaxis does not appear to prevent resistance. Further work remains to be done to elucidate the risk factors and optimal mode of prophylaxis and treatment for GCV-R CMV.

The development of cytomegalovirus (CMV) disease and subsequent emergence of drug-resistant strains was examined in a large group of solid organ transplant recipients; drug-resistant CMV was detected in a total of 30 transplant recipients (20 lung, 5 kidney, 4 heart, and 1 liver). Drug resistance was confirmed both phenotypically and genotypically. The sequences of drug-resistant CMV strains from the same patient differed from drug-susceptible baseline sequences only at single sites previously confirmed to confer drug resistance. At least 1 isolate from each patient had a mutation in the UL97 phosphotransferase coding sequence. Mutations in the DNA polymerase gene were found in 6 of 38 sequenced strains. Lung transplant recipients had the highest incidence of drug-resistant virus: of the 30 patients, 28 were CMV-seronegative transplant recipients of CMV-seropositive organs, which strongly supports the premise that drug resistance is most prevalent in that transplant population.

One hundred BacT/ALERT blood culture bottles growing gram-positive cocci in clusters were cultured and studied by LightCycler PCR for the sa442 and mecA genes. PCR was 100% sensitive and specific for detecting Staphylococcus aureus and methicillin resistance in S. aureus but was less accurate for methicillin resistance in coagulase-negative staphylococci.

Complications occurring > 1 month after Candida glabrata fungemia have not been studied. We conducted a study to determine the frequency and morbidity of complications of C. glabrata bloodstream infections occurring > 1 month after infection. Late complications were common (incidence 9.9 per 100 patient years), and most often occurred within the first year. In a multivariate analysis, late complications were associated with the presence of diabetes mellitus [odds ratio (OR) 12.2; 95% confidence interval (CI) 1.2-130] and chronic renal failure (OR 14.7; 95% CI 1.2-184). These data suggest that careful long-term follow-up of patients with C. glabrata fungemia is important and present an opportunity to explore secondary prophylaxis.

We report a case of livedo reticularis as an unusual complication of a midline catheter in a patient being treated for pyelonephritis with intravenous antibiotics. The rash resolved completely after catheter removal. The constellation of symptoms suggested an aberrant autonomic response as the cause of the illness.

New recommendations advise starting highly active antiretroviral therapy (HAART) slightly later in the course of HIV disease compared with earlier guidelines. HAART has prolonged life in HIV patients, altering the spectrum of problems being treated. As the immune system recovers, long-term prophylaxis against some secondary infections can be discontinued. The problem, however, is that HAART also has serious long-term side effects such as lactic acidosis, lipodystrophy, and the promotion of drug-resistant strains of HIV.

Purpose: Proven clinical efficacy of protease-sparing regimens (PSR) has been shown. Concerns exist about broad applicability of these regimens in advanced naïve patients. Recent reports have associated a rise in liver enzymes with nevi rapine; however, no data exist with efavirenz., Method: 17 consecutive antiretroviral-naïve HIV patients were started on a PSR with efavirenz plus two nucleoside reverse transcriptase inhibitors. Baseline liver enzymes, serum CD38, CD4, and HIV viral load data were collected. Correlation between change in viral load and immune reconstitution on therapy were compared to baseline laboratory values., Results: All patients had a mean viral load decrease of >2 logs, including patients with low initial CD4% or high viral load, and there was no increase of liver enzymes observed at a median follow-up of 42 weeks (range 17-78). There was a perfect correlation between the change in viral load and the initial viral load (p <.0001, r = 1.00) including patients with viral load > or =100,000 copies/mL and CD4 count< or =50 (n = 5). Even patients with low initial CD4 had a significant percentage increase in CD4 count (p <.0002, r = 0.7880). CD38% showed a positive correlation with change in viral load (p =.046, r = 0.522)., Conclusion: All patients experienced a mean viral load decrease of >2 logs (88% less than 400 copies/mL and 35% less than 20 copies/mL). There were no observed increases in liver enzymes. Patients with low CD4 counts, high initial viral load, or high CD38 expression still experienced a significant change in viral load.

For the primary infection of genital herpes, antiviral therapy with acyclovir is the gold standard. For recurrences, there are two options: antiviral treatment of each outbreak as it arises, or suppression of outbreaks with daily oral therapy. Patients tend to prefer the latter because it can decrease the number and severity of outbreaks, but it increases asymptomatic viral shedding and, therefore, the risk of unwittingly transmitting herpes simplex virus to uninfected sexual partners.

Context: Serological markers for the hepatitis B virus are routinely used in the evaluation of potential organ donors. However, serological tests can be associated with significant false or equivocal results and may not be indicative of the true risk of hepatitis B infection. Studies have recently questioned the significance of an isolated hepatitis B core antibody test in evaluating the suitability of solid organs for transplantation. The ability to detect hepatitis B virus DNA may prove useful when the diagnosis of hepatitis B infection is in doubt., Design: Serum samples from 16 donors with equivocal or positive hepatitis B core antibody and/or hepatitis B surface antigen serological screening tests were retrospectively tested for the presence of hepatitis B DNA. Any available follow-up data on the placement of organs from these donors was obtained., Results: One of the 16 (6.3%) donors tested positive for the presence of hepatitis B DNA, but organs from this donor were not recovered or transplanted. Follow-up on 14 organs recovered and transplanted from 6 donors in this group did not show clinical and/or laboratory evidence of hepatitis B infection in the recipients., Conclusions: In our donor population, there was a low incidence (6.3%) of donors with equivocal or positive hepatitis B core antibody and/or hepatitis B surface antigen serological screening tests who subsequently demonstrated the presence of detectable hepatitis B DNA. Posttransplantation follow-up of the recipients of 14 recovered organs failed to demonstrate any cases of posttransplant hepatitis B infection.

Candida species are now the fourth leading cause of nosocomial bloodstream infection in hospitalized patients, and non-Candida albicans species now surpass Candida albicans. The clinical features of the most common non-Candida albicans species, Candida (Torulopsis) glabrata, have not been well studied. We retrospectively reviewed the clinical features of 139 patients with C. glabrata blood-stream infection over a period of 7 years. The mean age of patients was 62 years, and the most common admitting diagnoses were malignancy (28%) and coronary artery disease (18%). The most common identified portals of entry were abdominal (22%) and intravascular catheters (16%). At the time of fungemia, 63% of patients had fever, 45% had change in mental status, and 30% were in septic shock. Three of 50 patients examined by an ophthalmologist had chorioretinitis. The overall hospital mortality was 49%. Factors associated with increased mortality in a regression model were prior abdominal surgery (odds ratio [OR] = 2.8; 95% confidence interval [CI] = 1.2-6.3, p = 0.01), and an elevated creatinine (OR = 2.2; 95% CI = 1.0-4.7, p = 0.05). When early deaths (< or = 72 hours) were censored, amphotericin B treatment and total dose were associated with reduced mortality (OR = 0.2; 95% CI = 0.1-0.4, p < 0.001). Nosocomial C. glabrata fungemia is not just a disease of debilitated and neutropenic patients, but affects a wide variety of patients and is associated with a high mortality.

The advent of highly active antiretroviral therapy (HAART) has brought about a dramatic decline in opportunistic infections, hospitalizations, and mortality in AIDS patients. However, the recent discovery that HIV can lay dormant in quiescent T cells and other tissues even in the face of HAART therapy has dampened optimism for a cure for AIDS, though it suggests new avenues of research.

Background: Microsporidia are the most common cause of chronic diarrhea in patients infected with human immunodeficiency virus. Patients who have undergone organ transplantation may also be infected. The precise immune defect and the clinical picture in transplant patients have not been studied., Methods: We report a case of microsporidia infection in a heart transplant patient and review three other cases reported in the literature., Results: Infection in three solid organ transplant patients occurred when the patients were receiving immunosuppressive therapy for rejection 1.5-3 years after transplantation. Patients had chronic diarrhea, vomiting, dyspepsia, and weight loss for 1 month to 3 years., Conclusions: Microsporidia may be the cause of chronic unexplained diarrhea and gastrointestinal disturbances in transplant patients. Defects in cell-mediated immunity probably play a role in maintaining the chronicity of this infection. Specific screening requests should be made to the microbiology laboratory when microsporidia infection is suspected.

Wound infections with Mycoplasma species are unusual; diagnosis may be delayed because of the growth characteristics of this organism. We report Mycoplasma hominis infection of sternotomy wounds in two patients. The first presented with fever and drainage from the incision 1 week after coronary artery bypass grafting. The other patient presented with drainage from the incision three weeks after double-lung transplantation. In both cases, initial cultures were negative, but the typical colonial morphology of M. hominis was subsequently detected. Successful treatment consisted of debridement and long courses of antibiotic therapy; omental flap grafting was eventually required for the second patient. Other published cases were reviewed and compared with the newly reported cases.

Over the years, there has emerged a considerable body of evidence supporting the importance of antimicrobial therapy in exacerbations of chronic bronchitis. The following lines of evidence suggest that most acute exacerbations are caused by bacterial infection: (1) the individual with chronic bronchitis is susceptible to bacterial infection as a consequence of local damage from prolonged cigarette smoking; (2) subtle defects in the local immune system can be shown, including impaired particle transport, defective immunoglobulin A production, chronic mucous impaction, and defective neutrophil phagocytosis; (3) acute bronchitic exacerbations are associated with a proliferation of pathogenic bacteria in the lower respiratory tract, based on quantitative culture data obtained by bronchoscopy with a protected specimen brush; (4) viral respiratory infections, which were once linked to over 50% of purulent exacerbations, probably account for only a minority of bronchitic exacerbations; (5) some "culture negative" exacerbations may be caused by bacteria susceptible to antibiotics such as Mycoplasma pneumoniae or Chlamydia pneumoniae. There are also secondary effects of bacteria that are potentially amenable to antibiotic therapy. Bacteria that colonize the respiratory tract of chronic bronchitics cause direct damage to the respiratory epithelium. Lipooligosaccharide, a major component of the outer membrane of Haemophilus influenzae, is an endotoxin-like mediator of respiratory cell damage. The host inflammatory response to bacterial proliferation is ineffective and may be potentially harmful; the enzyme neutrophil elastase is released by the host during phagocytosis of bacteria and may lead to progressive airway damage. In addition, bacterial superinfections may complicate viral exacerbations of chronic bronchitis. Clinical trials examining the efficacy of antibiotic therapy in mild to moderate exacerbations of chronic bronchitis have yielded conflicting results, caused in part to fundamental differences in study design. The major double-blinded and placebo-controlled studies suggest a trend in favor of antimicrobial therapy, although the effect is modest. For the individual patient, the risks of antimicrobial therapy are small compared with the potential benefits of returning to work earlier and avoiding the rare case of respiratory decompensation.

A cottony, light tan, filamentous fungus with pear-shaped microconidia and lacking tuberculated macroconidia was isolated from a bronchial lavage specimen. Subculture on several media at 37 degrees C failed to convert the fungus to a yeast form after several weeks; attempts at in vivo conversion in mice were also unsuccessful. Sera obtained several months apart showed M bands with Histoplasma capsulatum (HC) antigen by immunodiffusion and an increase in complement fixation titers with mycelial and yeast phase antigens of HC. Parallel identity was obtained on two occasions with exoantigen culture confirmation reagents for HC from Immuno-Mycologics as well as one of identity with Nolan reagents. Extracts from four Chrysosporium spp. strains had no identity reactions with HC with either kit. The fungus was identified as HC by the Accuprobe Histoplasma chemiluminescence-labeled DNA probe directed at ribosomal RNA, whereas all four Chrysosporium spp. isolates tested negative. DNA probes are a fast and accurate method to confirm the identity of aberrant fungal isolates.