Persistently positive culture results in a patient with community-acquired pneumonia due to Legionella pneumophila.

We describe a patient with community-acquired pneumonia due to Legionella pneumophila serogroup 6. This patient was found to have bronchoalveolar carcinoma of the lung by means of cytologic testing in 1 of 2 bronchoalveolar lavage samples, but no lesions were visible on bronchoscopy. Despite intravenous administration of azithromycin to the patient, repeat culture and polymerase chain reaction showed persistence of Legionella; the isolates remained susceptible to azithromycin. The patient did not respond to 14 doses of daily intravenously administered azithromycin. The poor outcome may have been partially due to the suspected underlying lung malignancy, as shown by cytologic examination, and by a delay in seeking medical attention.

Recurrent pneumococcal bacteremia: 34 episodes in 15 patients.

Thirty-four episodes of pneumococcal bacteremia were identified in 15 patients over 5 years in 10 hospitals in Franklin County, Ohio. Twelve patients each had 2 episodes of pneumococcal bacteremia, 2 had 3, and 1 had 4. All patients had predisposing conditions, with lymphoma, multiple myeloma, and chronic obstructive pulmonary disease being the most frequent. The mean interval between the first and second episode was 268 days. Serotyping and genotyping were performed on 29 isolates. The same serotypic and genotypic patterns were found for sequential isolates from four patients; three of these patients had a recurrence between 22 and 90 days after a previous episode. Seven (24%) of the 29 isolates were serotype 23F; four isolates (14%) were not susceptible to penicillin. All of our patients received appropriate antimicrobial therapy and appeared to be clinically cured of their initial infection. For patients with recurrent pneumococcal disease, alternate preventive measures such as immunization with conjugate pneumococcal vaccine and/or prophylactic antibiotic therapy should be considered.

A study of HIV RNA viral load in AIDS patients with bacterial pneumonia.

We examined the effect of bacterial pneumonia on the magnitude of circulating plasma HIV RNA in HIV-infected patients. Serum samples from 13 adult HIV-infected patients (median CD4 count = 83 cells/microl) were assayed for HIV RNA using the reverse transcriptase polymerase chain reaction assay (a) before bacterial pneumonia, (b) during the acute phase, and (c) after the recovery from the disease. Patients remained on constant antiretroviral therapy: HIV RNA was detected in all samples tested. The medians before, during, and after bacterial pneumonia were 60,000 copies per ml, 245,000 copies per ml, and 84,000 copies per ml, respectively. All 13 patients had increased HIV RNA levels on developing pneumonia. There was a decline in the level of HIV RNA with recovery from pneumonia in 12 of 13 patients. The difference between the HIV RNA levels before and after pneumonia was not significant, nor was there significant difference in the CD4 counts before and after pneumonia. In conclusion, bacterial pneumonia is associated with a consistent, transient increase in HIV RNA of variable magnitude in AIDS patients. Interpretation of HIV RNA changes for clinical management of AIDS patients must take into account this reversible elevation during infections.

Frequencies of opportunistic diseases prior to death among HIV-infected persons. Community Programs for Clinical Research on AIDS.

OBJECTIVES: To describe the complete history of major opportunistic events experienced by 1883 HIV-infected persons prior to and specifically within 6 months of death, and to determine whether the frequency of specific events varies according to demographic characteristics, risk behaviors or geographic location. DESIGN: Descriptive case series. METHODS: Of 6682 HIV-infected individuals enrolled in studies sponsored by the Community Programs for Clinical Research on AIDS between September 1990 and June 1994, 1883 died during follow-up. A complete history of AIDS-defining events was determined for these patients by combining medical history data obtained at the time of enrollment, new events that occurred during follow-up, and causes of death. RESULTS: The most common opportunistic AIDS-defining events these 1883 patients experienced before death were Pneumocystis carinii pneumonia (PCP; 45%), Mycobacterium avium complex (MAC; 25%), wasting syndrome (25%), bacterial pneumonia (24%), cytomegalovirus (CMV) disease (23%) and candidiasis (esophageal or pulmonary; 22%). In addition, 47% of patients experienced two or three AIDS-defining events before death, and 22% experienced four or more events. In the 6 months prior to death, 22% of patients had PCP, 21% had MAC, and 20% had CMV disease. Significant sex and ethnic differences were found: bacterial pneumonia occurred more often before death in women compared with men; fewer blacks and Latinos than whites experienced Kaposi's sarcoma (KS); and fewer blacks than whites had CMV disease before death. The percentage of patients with KS and CMV also varied by risk behavior. The frequency of 10 opportunistic diseases varied by geographic region after adjustment for demographic characteristics and risk behavior. Of note, many more patients in northeastern USA had tuberculosis and fewer had MAC. CONCLUSION: A large percentage of individuals with HIV infection experienced multiple AIDS-defining opportunistic diseases before death. PCP, MAC, wasting syndrome, bacterial pneumonia, CMV disease, and candidiasis (esophageal or pulmonary) account for a substantial proportion of morbidity associated with HIV infection. More diseases varied by geographic location than by demographic characteristics or risk behavior of patients. Continued research on the etiology and prevention of these diseases and how they relate to one another should be a high priority.

Selective inhibitory effects of stress hormones on natural killer (NK) cell activity of lymphocytes from AIDS patients.

To examine the potential role of stress hormones in the progression of HIV infections, we developed an in vitro model system that investigates the effects of cortisol, adrenocorticotropin-releasing hormone (ACTH) and beta-endorphin on the natural killer cell activity of lymphocytes from normal subjects and AIDS patients. The system employs a 4 hr 51Cr release assay and K562 target cells. Direct addition of cortisol (0.05, 0.1, and 0.2 microgram/ml) or ACTH (10(-6) to 10(-8) M) to the mixture of effector and prelabeled target cells did not produce any significant immunoregulatory effects on the NK cell activity of normal lymphocytes. Direct addition of beta-endorphin (10(-13) to 10(-17) M) to the mixture of effector and prelabeled target cells did not produce any significant immunoregulatory effects on the NK cell activity of lymphocytes from normal or AIDS subjects. However, cortisol and ACTH significantly inhibited the NK activity of lymphocytes from AIDS patients. The selective inhibitory effects of cortisol and ACTH in patients with HIV infections are consistent with a model which proposes that stress related neurohormones and/or neuropeptides may be involved in the progression of HIV infections.

Clinical safety, tolerability, and pharmacokinetics of murine monoclonal antibody to human tumor necrosis factor-alpha.

The safety, tolerability, and pharmacokinetic profile of murine monoclonal antibody to human tumor necrosis factor-alpha (TNF alpha MAb) were evaluated in 20 uninfected patients at risk of sepsis and 16 septic patients. TNF alpha MAb was well tolerated in all patients, with no immediate or delayed signs of allergic reaction. During the 28-day evaluation, side effects included thrombocytosis (11), hepatic enzyme elevations (8), cardiac arrhythmias (3), and deaths (5). Each was attributed to the patient's severe underlying disease and not to TNF alpha MAb; however, a relationship between TNF alpha MAb and these events cannot be ruled out. The half-life was 52 h for a single infusion of TNF alpha MAb. Human antibody against TNF alpha MAb was observed in 13 (76.5%) of 17 phase IA patients and 10 of 10 phase IB patients and anti-idiotype antibodies in 11 (91.7%) of 12 phase IA patients and 2 (33.3%) of 6 phase IB patients. TNF alpha MAb should be evaluated as adjunctive therapy for patients with sepsis.

Health care worker exposure to HIV-1 and HTLV I-II in critically ill, resuscitated emergency department patients.

STUDY OBJECTIVE: Exposure to HIV-1 is of profound concern to health care workers. HTLV-I and HTLV-II, retroviruses with similar modes of transmission as HIV-1, also cause disease in human beings. Emergency department resuscitations are high-risk situations for such exposure. The purpose was to determine the seroprevalence of HIV-1 and HTLV I-II in patients undergoing ED resuscitations, the magnitude of health care worker exposure, and risk factors associated with infection. DESIGN: Prospective identity-unlinked seroepidemiologic study. SETTING: ED of a 950-bed private inner-city teaching hospital. Participants included 370 patients undergoing ED resuscitations. MEASUREMENTS: Serum was tested for antibodies to HIV-1 and HTLV I-II. Questionnaires were completed by the physician in charge of the ED resuscitations. RESULTS: Fifteen (4.1%) (95% confidence interval [CI], 2.1% to 6.1%) patients were HIV-1 seropositive, and seven (1.9%) (95% CI, 0.7% to 3.1%) were HTLV I-II positive. Eleven (5.6%) (95% CI, 2.4% to 8.8%) of 197 trauma patients and 11 (6.4%) (95% CI, 2.8% to 10.0%) of 173 medical patients were infected with one of these viruses. Health care workers had direct cutaneous contact with patient blood during 114 (31%) ED resuscitations and with infected patient blood during 11 (3%) ED resuscitations. An additional 11 ED resuscitations involved parenteral exposures, one to HIV-1-infected blood. No factors could be identified that would quickly and reliably predict infection. CONCLUSION: Health care workers must protect themselves in such high-risk situations by strict compliance to mandatory universal precautions.

The emerging role of HTLV-I/II and HIV-1 among intravenous drug users in Detroit.

During 1987-1988, a seroprevalence study of the human immunodeficiency virus (HIV-1) and the human T-cell lymphoma/leukemia virus (HTLV-I/II) was performed among Detroit intravenous drug users unaffiliated with substance abuse programs. Seroprevalence data along with patient demographic information were compared to a similar study performed in 1985-1986. In the earlier study, 12 (12.5%) of 96 individuals tested positive for HIV-1. Of the 74 available negative samples retested in 1987-1988 for retroviruses, 7 (9.5%) tested positive for HTLV-I/II. Thus, the overall retroviral (HIV-1, HTLV-I/II) seropositive rate for 1985-1986 was 22%. In 1987-1988, 11 (15.7%) of 70 individuals tested positive for HIV-1 and 7 (10%) tested positive for HTLV-I/II. Concomitant infection with both viruses was found in 2 (2.9%) of the 70 individuals. Thus, retrovirus seroprevalence in 1987-1988 was 22.9%. In 1987-1988, significant differences between the retroviral-positive group and the retroviral-negative group consisted of intravenous drug use greater than 16 years (P = 0.059) for an odds ratio of 3.80 (CI 1.12-12.89) and sex with female prostitutes (P = 0.029) for an odds ratio of 5.38 (CI 1.38-20.95).

The role of tumor necrosis factor in sepsis.

There is an increasing incidence of sepsis among hospitalized patients. Also, high mortality associated with sepsis and septic shock persists despite appropriate antibiotic therapy. Recent investigations have demonstrated that bacterial antigens stimulate a cascade of cellular mediators or cytokine release. In sepsis and septic shock the response of these cytokines often exceeds natural downregulation and leads to multisystem organ failure and even death in an unacceptably high number of patients. Many investigative studies have shown that tumor necrosis factor (TNF) is the prime mediator of the inflammatory response seen in sepsis and septic shock. Sepsis management in the future will include immune modulating therapy directed against the deleterious effects of cytokines, specifically TNF. This article reviews the current problem of sepsis and the evidence to support the role of TNF in sepsis. also, recent studies employing monoclonal antibodies against TNF as well as considerations for future studies are discussed.

Emphysematous gastritis: case report and review.

Emphysematous gastritis is a condition involving gastric wall inflammation, radiologic or intraoperative evidence of intramural gas, and systemic toxicity. A recent case of emphysematous gastritis in a 57-year-old diabetic man is reported, and 27 cases published since 1889 are reviewed. Predisposing factors include ingestion of corrosive substances (37%) and alcohol abuse (22%). Diagnosis of emphysematous gastritis is based on the clinical presentation of an acute abdomen with systemic toxicity and on radiographs demonstrating gas bubbles within the stomach wall. For the case reported herein, computed tomography was useful both in establishing the diagnosis and in following the resolution of emphysematous gastritis. Organisms most commonly involved were Escherichia coli (six cases), Streptococcus species (six cases), Enterobacter species (five cases), and Pseudomonas aeruginosa (three cases). The mortality was 61% (17 of 28 patients), and morbidity with gastric contractures occurred in 21% of cases (6 of 28). Optimal therapy has not been defined; however, antimicrobial chemotherapy and surgery, when appropriate, may improve survival rates.

Inhibition of Legionella pneumophila multiplication within human macrophages by fleroxacin.

The susceptibility of Legionella pneumophila to a new quinolone, fleroxacin, was studied in both an extra- and an intracellular system. The activity of fleroxacin was compared with that of erythromycin, cefoxitin, and rifampicin. In the extracellular system, erythromycin inhibited while cefoxitin killed the organism. Extracellularly, fleroxacin performed similarly to cefoxitin. Rifampicin was initially bactericidal for L. pneumophila but resistant bacteria emerged at 48 h. The Horwitz monocyte model was used for studies of intracellular antimicrobial activity. At ten times the MIC, cefoxitin did not inhibit intracellular L. pneumophila. Fleroxacin was as active as erythromycin and rifampicin in inhibiting intracellular L. pneumophila. No intracellular, rifampicin-resistant L. pneumophila emerged. Addition of rifampicin to cefoxotin, erythromycin or fleroxacin provided neither synergy nor antagonism.

Infection surveillance in cardiac transplantation.

Infections are a major cause of morbidity and mortality in cardiac transplantation. There is little information describing screening and prospective surveillance of heart recipients. We describe a surveillance program that was used for 35 patients, which screens and follows recipients through serologic, virologic, and immunologic parameters. Pretransplantation surveillance identified four (11.4%) patients whose skin tests with purified protein derivative (PPD) were positive, one patient with giardiasis, and seven (20%) recipients who were susceptible to cytomegalovirus (CMV). Twelve (34.3%) patients had CMV infections, only one of which was primary and involved a seropositive donor. The low rate of primary infection (14%) may result from our use of CMV-negative blood products. Seven (20%) recipients who were seronegative for toxoplasmosis received seropositive hearts, and disseminated toxoplasmosis developed in one of them. Eight (22.8%) patients had asymptomatic significant increases in Epstein-Barr virus antibody titers, without evidence of lymphoma. Fifteen (42.8%) recipients had at least one herpes simplex virus reactivation. Preventive, diagnostic, and early therapeutic interventions should occur as a result of infection surveillance, thus leading to a reduced risk of infection during the period after cardiac transplantation.

In-vitro susceptibility of gram-positive cocci to LY146032 teicoplanin, sodium fusidate, vancomycin, and rifampicin.

LY146032, a new antimicrobial agent with activity against Gram-positive cocci, was tested against methicillin-susceptible and methicillin-resistant Staphylococcus aureus, methicillin-susceptible and methicillin-resistant Staph. epidermidis, Staph. saprophyticus, and Streptococcus faecalis. MIC90s in cation-supplemented Mueller Hinton broth by the microdilution broth method were less than 1.0 mg/l for all organisms tested. Increasing or decreasing the inoculum size did not appreciably effect the MIC50 or MIC90 for any organism group nor did decreasing the incubation temperature. The addition of sodium chloride to the test system did not appreciably effect the susceptibility of methicillin-resistant Staph. aureus to LY146032. All organisms were 4 to 32 times more susceptible to LY146032 than to vancomycin. The Staph. aureus had LY146032 susceptibility patterns which were similar to those of teicoplanin and sodium fusidate. LY146032 was 4-16 times more active than teicoplanin against Staph. saprophyticus and Staph. epidermidis while teicoplanin was 8-16 times more active than LY146032 against Str. faecalis.

The in-vitro and in-vivo efficacy of cisplatin and analogues in the treatment of herpes simplex virus-II infections.

The antitumour effect of cisplatin results from cross-linking and disruption of DNA when it binds to DNA bases, especially cytosine and guanine. Since herpes simplex virus (HSV) has a high cytosine and guanine content, cisplatin might be expected to have an antiviral effect against HSV. The 50% inhibitory concentration of cisplatin for HSV-II was 0.06 mg/l. Six of ten platinum analogues had 50% inhibition of plaques at less than or equal to 10 mg/l. We evaluated the in-vivo activity of cisplatin against the MS strain of HSV-II in the mouse genital HSV model. Mice were treated either intraperitoneally or intravaginally beginning at 3 or 51 h after inoculation. In the intraperitoneally treated groups infection rates were lower, but not significantly; 4 of 15 in the 3-h and 7 of 15-h group, compared to 9 of 15 in the untreated control group (P greater than 0.18, chi-square test). Intravaginal cisplatin demonstrated a significant reduction of the infection rate from 10 of 15 untreated controls, compared to 5 of 18 in the 3-h and 5 of 17 in the 51-h group (P less than 0.05, chi-square test). No toxic effects of intravaginal cisplatin were seen in uninfected mice. These studies suggest that platinum containing drugs warrant further evaluation as a new class of antiviral agents with activity against HSV.

The effect of heat upon the interaction between aminoglycosides and semi-synthetic penicillins in human serum: a consideration for HIV infectious serum.

We conducted 2 experiments to study the effect of heat on the interaction between aminoglycosides and semi-synthetic penicillins in human serum. In one experiment, human serum spiked with either gentamicin or tobramycin at a concentration of 4.7 mg/l plus carbenicillin, ticarcillin, piperacillin, mezlocillin, or azlocillin at concentrations of either 50 mg/l or 150 mg/l was subjected to a 30-min, 56 degrees C waterbath incubation. In the second experiment, randomly selected sera from patients receiving either gentamicin or tobramycin were also heat-treated. Two methods, the Abbott TDx and the Syva Emit, were used for each aminoglycoside assay. The difference between pre- and post-heat treatment aminoglycoside concentration was less than 10% in approximately 92% of the patient sera and in 93% of the spiked sera containing an aminoglycoside plus a semi-synthetic penicillin at 50 mg/l. For sera spiked with an aminoglycoside plus a semi-synthetic penicillin at 150 mg/l, post-heat treatment concentrations were 5-19% lower than pre-heat treatment concentrations. In most instances, heat treatment of sera does not alter aminoglycoside concentrations to any clinically significant degree.

In vitro susceptibility of gram-positive cocci to paldimycin.

Paldimycin (U-70138F) is a new antimicrobial agent with activity against gram-positive cocci. Clinical isolates of staphylococci and streptococci were tested. MICs were higher in Mueller-Hinton broth than in nutrient broth. Change in pH had minimal effect on the MICs in either broth. When inoculum size was varied, an inoculum effect was observed. The gram-positive cocci tested were generally more susceptible to paldimycin than to vancomycin.

Relative efficacy and toxicity of netilmicin and tobramycin in oncology patients.

We prospectively compared the efficacy and safety of netilmicin sulfate or tobramycin sulfate in conjunction with piperacillin sodium in 118 immunocompromised patients with presumed severe infections. The two treatment regimens were equally efficacious. Nephrotoxicity occurred in a similar proportion in patients treated with netilmicin and tobramycin (17% vs 11%). Ototoxicity occurred in four (9.5%) of 42 netilmicin and piperacillin and in 12 (22%) of 54 tobramycin and piperacillin-treated patients. Of those evaluated with posttherapy audiograms, three of four netilmicin and piperacillin-treated patients had auditory thresholds return to baseline compared with one of nine tobramycin and piperacillin-treated patients. The number of greater than or equal to 15-dB increases in auditory threshold as a proportion of total greater than or equal to 15-dB changes (increases and decreases) was significantly lower in netilmicin and piperacillin- vs tobramycin and piperacillin-treated patients (18 of 78 vs 67 of 115). We conclude that aminoglycoside-associated ototoxicity was less severe and more often reversible with netilmicin than with tobramycin.

Comparison of intravenous administration with intrauterine irrigation with ceforanide for nonelective cesarean section.

A randomized, prospective, double-blind study was designed to compare intravenous administration with intrauterine irrigation using an extended half-life (t1/2 = three hours) cephalosporin, ceforanide. Patients included in the study had a nonelective cesarean section with rupture of membranes for three hours or longer. Sixty-four patients received a single dose of ceforanide immediately after clamping the umbilical cord. Patients were similar in both groups in age, weight, length of labor, and duration of ruptured membranes. The group receiving the intravenous ceforanide had a significantly shorter duration of surgery than the patients receiving the intrauterine ceforanide. Endometritis infection rates were similar, 11.8% (intravenous) versus 11.1% (intrauterine), P greater than .1. Serum levels were as much as tenfold higher in the intravenous group versus the intrauterine group. Intrauterine irrigation with an antimicrobial agent provided no advantage over systemic administration.