Group G streptococcal endocarditis.

The group G streptococcus may be a more common human pathogen than previously recognized. A case of group G streptococcal endocarditis is reported and the 11 cases reported previously are reviewed. Group G endocarditis may have significant clinical and prognostic differences from endocarditis caused by the more commonly identified viridans or group D streptococci. Routine serologic grouping of beta-hemolytic streptococcal isolates from serious infections is warranted.

The non-value of preoperative and intraoperative cultures in predicting the bacteriology of subsequent wound infection in patients undergoing major head and neck cancer surgery.

A prospective study of patients undergoing major head and neck cancer surgery was undertaken to define the value of preoperative and intraoperative cultures in identifying the patient at "high risk" of wound infection and in predicting the bacteriology of wound infection. One or two days before surgery, the skin of the operative site on the neck, the oropharynx and anterior nares were swabbed. an intraoperative wound culture was obtained after the pharyngeal defect was closed and the wound irrigated with water. All cultures were processed for aerobes in the Anaerobic Bacteriology Research Laboratory at Wadsworth Hospital Center. Wound infections developed in 10 of 31 patients who received cefazolin prophylactically and 21 of 25 patients who received no perioperative antibiotics. Fifty-five percent of infected patients and 68% of noninfected patients demonstrated potential pathogens preoperatively. A potential pathogen isolated preoperatively or intraoperatively was subsequently recovered from 35% of infected wounds. The majority of infected wound cultures grew one or more additional pathogens. A poor correlation was also noted between preoperative nasal Staphylococcus aureus isolation and subsequent recovery from wound infections. We conclude that preoperative and intraoperative aerobic wound cultures are not predictive of the "high risk" patient or of the bacteriology of subsequent wound infection in major head and neck cancer surgery.

Overview of infectious diseases and other nonmalignant conditions in the acquired immune deficiency syndrome.

Treatment of an AIDS patient with opportunistic infections is clearly complicated by the immunological and nutritional deficiencies associated with the syndrome. Clinical control of some individual infections may be achieved with traditional or investigational measures, but relapse or appearance of another serious infection may be expected within months in most patients. While progress has been made in the treatment of infections such as those discussed in this paper and elsewhere in this symposium, 'successful' treatment of an opportunistic infection in a patient with AIDS is comparable to achieving a remission in a patient's cancer. Such 'successful' treatment in no way implies cure or even control of the acquired immune deficiency itself.

Anaerobes in infections of the head and neck and ear, nose, and throat.

Anaerobic bacteria outnumber aerobes at most oropharyngeal sites, with counts up to 10(11)/ml of fluid, and have been implicated in infections of all structures of the head and neck. They are common in chronic otitis media, chronic sinusitis, and various soft-tissue infections. These infections are initiated primarily by mucosal breaks. Bacterial factors such as adhesiveness and antileukocytic activity also may play a role. Among the complications of these infections are brain abscess, aspiration pneumonia, and anaerobic sepsis. Treatment includes surgical drainage and use of antimicrobial agents active against the mixed flora commonly found. Penicillin is currently the drug of choice, but this may change with the emergence of beta-lactamase-producing strains of anaerobes such as Bacteroides melaninogenicus.

An acquired cell-directed inhibitor of neutrophil chemotaxis and hypogammaglobulinemia.

An unusual combination of host defense abnormalities was demonstrated in an adult male with recurrent pulmonary infections due to a variety of microorganisms. Polymorphonuclear neutrophil chemotaxis was defective. Other neutrophil and T-lymphocyte function tests were normal. The patient's serum also showed a severe deficiency of IgG, no detectable IgA, IgM, or IgD, and increased IgE. The chemotactic defect was shown to be due to a cell-directed inhibitor in the patient's serum. The effect of the inhibitor on chemotaxis could be antagonized by factors in normal serum. The chemotaxis defect persisted for several months, but eventually returned to normal.

Activity of combinations of antimicrobial agents against Bacteroides fragilis.

Thirty-two clinical isolates of Bacteroides fragilis were tested against nine pairs of antimicrobial agents by means of an agar dilution technique. A synergistic effect was observed with the combination of clindamycin and metronidazole. End points were achieved with 17 strains. Of these strains, 13 (76%) were inhibited by the combination of clindamycin and metronidazole; each drug was present at a concentration of less than or equal to 25% of its minimal inhibitory concentration when tested alone. This combination also showed synergistic bactericidal activity against three of six strains examined by a tube dilution technique. No antagonism was noted with any strain. The other eight combinations tested failed to show a consistent synergistic effect, although no antagonism was observed. These in vitro data indicate that antagonism is not likely to be encountered when combination therapy is used for B. fragilis infections. For selected B. fragilis infections, the combination of clindamycin and metronidazole may be useful.

Anaerobic and aerobic bacteriology in head and neck cancer surgery.

A prospective study of wound infections following major head and neck cancer surgery was undertaken to define a rational approach to trials of antibiotic prophylaxis and initial therapy of these infections. Preoperative aerobic cultures were taken from the planned site of skin incision and from the oropharynx. Both aerobic and anaerobic cultures were obtained from all wound infections. Patients receiving prophylactic antibiotics were excluded from the study. The data indicate that preoperative cultures are not usually predictive of the bacteriology of subsequent wound infection. Mixed aerobic and anaerobic flora were cultured from most wound infections and usually reflected normal anaerobic oropharyngeal flora and/or exogenously acquired Staphylococcus aureus. Bacteroides fragilis was not cultured in this series. Antibiotics selected for trials of prophylaxis or initial treatment of these infections should cover both the resident oral aerobic and anaerobic flora and S aureus. Coverage for B fragilis does not appear necessary. Antibiotic choices might include (1) penicillin G agents plus a penicillinase-resistant penicillin or (2) a parenteral cephalosporin.

Cefoxitin for treatment of infections due to anaerobic bacteria.

Twenty-seven patients with 29 infections due to anaerobic or mixed anaerobic-aerobic bacteria were treated with cefoxitin. From the 27 patients 99 isolates of anaerobic bacteria and 70 isolates of aerobic bacteria were recovered. Twelve pleuropulmonary infections, 12 soft tissue infections, three bone infections, and two intraabdominal infections were treated. Twenty-six of the 29 infections were completely or partially eradicated; the remaining three infections were unchanged. One-third of the patients experienced phlebitis; in two instances severe phlebitis caused discontinuation of therapy. In this study cefoxitin appeared to be an effective single agent for the therapy of infections due to specific anaerobic bacteria or to a mixed flora of anaerobic and aerobic bacteria.

Cefoxitin: clinical evaluation in thirty-eight patients.

Clinical and bacteriological efficacy, patient tolerance, and toxicity of cefoxitin, a beta-lactamase-resistant cephamycin, were evaluated in 38 patients; 13 had soft tissue infection, 12 had pneumonia, 3 had urinary tract infection, 2 had peritonitis, and 4 had miscellaneous infections. In five patients, infection was clinically evident, though not bacteriologically proven. The latter patients were evaluated with regard to tolerance and toxicity only. Among the 34 infections in 33 patients, 71% were considered clinically cured; 86% of those patients who could be recultured were bacteriologically cured. Phlebitis was noted in 32% of the total group, and eosinophilia was observed in 16%. Unexplained deterioration in renal function occurred in two patients. Mean peak cefoxitin levels in serum were 72 mug/ml 30 min after a 2-g infusion and 32 mug/ml 30 min after a 1-g infusion. Cefoxitin was more active against facultatively and obligately anaerobic gram-negative organisms isolated from these patients than was cephalothin.

Susceptibility of respiratory tract anaerobes to orally administered penicillins and cephalosporins.

Anaerobic bacteria recovered from airway-related infections were tested by agar dilution against selected penicillins and cephalosporins available for oral administration. Against 136 isolates, penicillins G and V showed comparable activity, particularly when pharmacological differences were considered. Although many isolates were exquisitely susceptible to the penicillins, only 55% of the Bacteroides species and 72% of all isolates were inhibited at 0.5 mug of penicillin G per ml. Results for penicillin V at 1 mug/ml were similar (59 and 73%). The two cephalosporins were more active at achievable levels, inhibiting 94 to 95% of Bacteroides and 95 to 96% of all isolates at 8 mug/ml. These levels represent approximately 50% of the reported peak serum levels after oral administration of 625 mg of the penicillins and 500 mg of the cephalosporins. Dicloxacillin and nafcillin were tested against 50 isolates. The two were comparably active on a weight basis; dicloxacillin was more active when pharmacological differences were considered, but did not match the other penicillins or the cephalosporins.

Ganciclovir treatment of cytomegalovirus colitis in AIDS: a randomized, double-blind, placebo-controlled multicenter study.

The efficacy and safety of ganciclovir therapy for cytomegalovirus (CMV) colitis in patients with AIDS was examined in a double-blind, placebo-controlled study. Sixty-two patients at four university medical centers were enrolled. All had biopsy-proven CMV colitis with diarrhea, fever, and weight loss. Other pathogens were excluded. Ganciclovir (5 mg/kg) or placebo was administered every 12 h for 14 days. A significant reduction in CMV-positive colonic and urine cultures was seen with ganciclovir (P = .034 and P < .001, respectively) compared with placebo. Colonoscopy scores were improved significantly more with ganciclovir than with placebo (P = .042). New extracolonic CMV disease developed in 7 (23%) of 30 placebo patients and in 3 (9%) of 32 ganciclovir patients in only 14 days (P = .026). Ganciclovir-treated patients maintained body weight, while placebo patients had a mean loss of 1.5 kg. Overall, ganciclovir appears of some benefit in treating CMV colitis in patients with AIDS.

Acquired immunodeficiency syndrome (AIDS)--apheresis and operative risks.

The removal of immune complexes, autoantibodies and suppressor factors from the circulation of patients with AIDS and AIDS related conditions by plasmapheresis and selective immunoadsorption may play a role as a therapeutic modality in these disorders. Lymphocytapheresis may also be of potential use in AIDS related conditions with presumed autoimmune basis. Perfusion of plasma over immobilized protein A columns is being evaluated as a possible immunomodulatory and antitumor therapy in patients with AIDS related Kaposi's sarcoma. Although apheresis procedures as a therapeutic modality in AIDS related conditions are still at the experimental stage, preliminary results are encouraging. The possible transmission of the disease by blood products presents a health hazard to health workers involved in the field of apheresis. Since the mode of transmission of the disease appears to be similar to hepatitis B, strict hepatitis B precautions should be enforced in every case in which AIDS suspected blood is being processed.

Doxycycline in abdominal surgery.

Twenty patients undergoing urgent or emergency surgical procedures where intra-abdominal infection was suspected were treated with doxycycline hyclate. Wound infections involving anaerobic, aerobic, or facultative bacteria developed in four of 11 patients treated with doxycycline alone. Nine other patients received higher doses of doxycycline plus gentamicin sulfate. Five of these had postoperative infections primarily involving anaerobic organisms. Bacteremia with a doxycycline-resistant Bacteroides fragilis developed in one patient during therapy. Serum levels of doxycycline, even at the higher dosage, were below the minimal inhibitory concentrations (MICs) of a number of potential pathogens isolated at the time of surgery. Doxycycline is not indicated in cases of serious intra-abdominal infection unless the infecting flora are known to be susceptible.

The use of plasmapheresis, lymphocytapheresis, and staph protein-A immunoadsorption as an immunomodulatory therapy in patients with AIDS and AIDS-related conditions.

Circulating immune complexes, autoantibodies, and suppressor factors to normal lymphoproliferation may play an important role in the induction and maintenance of the cellular immunodeficiency characteristic for the acquired immunodeficiency syndrome (AIDS) and its related conditions. In order to explore the possibility that the removal of circulating humoral factors may have an immunomodulatory effect in patients with AIDS and AIDS-related conditions (ARC), we used apheresis procedures to treat patients with different clinical presentations of AIDS and ARC. Five patients with AIDS and opportunistic infections were treated with plasmapheresis. Four patients with AIDS and Kaposi's sarcoma without opportunistic infections were treated with staph protein-A immunoadsorption and two patients with ARC and peripheral neuropathy were treated with lymphoplasmapheresis. The treatments were tolerated well by all patients. Effective removal of circulating humoral immune factors was observed in all three groups. No significant clinical benefit was seen in the patients with AIDS and opportunistic infections treated with plasmapheresis. Partial tumor responses were observed in three of the four patients with AIDS related Kaposi's sarcoma treated with staph protein-A plasma perfusion, and resolution of neurologic symptoms was seen in both patients with ARC and peripheral neuropathy treated with lymphoplasmapheresis. Our preliminary results suggest that lymphoplasmapheresis may be an effective treatment modality for patients with ARC related peripheral neuropathy, that protein-A immunoadsorption is well tolerated by patients with AIDS-related Kaposi's sarcoma, and that this treatment has antitumor and immunomodulatory effects in these patients.

Pharmacokinetic, safety, and antiviral profiles of oral ganciclovir in persons infected with human immunodeficiency virus: a phase I/II study. AIDS Clinical Trials Group, and Cytomegalovirus Cooperative Study Group.

A phase I/II study evaluated the pharmacokinetics, tolerability, and antiviral activity of oral ganciclovir in persons infected with human immunodeficiency virus (HIV). Oral bioavailability ranged from 2.6% to 7.3%. The mean maximum serum concentration achieved at 1000 mg every 8 h was 1.11 micrograms/mL, and mean trough level was 0.54 microgram/mL. The time to maximum serum drug concentration was 1.0-2.9 h, with a serum half-life of 3.0-7.3 h, suggesting prolonged oral absorption. Serious adverse events were uncommon. Decreased cytomegalovirus (CMV) shedding was observed from all sites. The median days (by dosage) to retinitis progression assessed by retinal examination after initiation of oral ganciclovir were 62 (1000 mg every 8 h), 148 (500 mg every 3 h), 75 (750 mg every 3 h), 148 (1000 mg every 3 h), and 139 (2000 mg every 8 h). Thus, oral ganciclovir has pharmacokinetic, toxicity, and antiviral profiles that may prove beneficial for both maintenance therapy of CMV retinitis and prevention of CMV disease in HIV-infected persons.

An outbreak of Pneumocystis carinii pneumonia in homosexual men.

Pneumocystis carinii pneumonia has rarely been reported in previously healthy persons over the age of 6 months. Five cases of P. carinii pneumonia in adult homosexual men, confirmed by biopsy results, are reported. All five patients were seropositive when tested for antibodies to cytomegalovirus and four had evidence of active concurrent cytomegalovirus infections. Kaposi's sarcoma was shown in two of the patients and one had possible Pneumocystis infection of the central nervous system as well as P. carinii pneumonia. Three patients had second episodes of Pneumocystis pneumonia. Four of the five patients have died. Past or concurrent cytomegalovirus infection and homosexuality were the only common epidemiologic features in all five patients.

A randomized, controlled study of intravenous ganciclovir therapy for cytomegalovirus peripheral retinitis in patients with AIDS. AIDS Clinical Trials Group and Cytomegalovirus Cooperative Study Group.

This prospective, randomized, multicenter, controlled trial was designed to evaluate the efficacy and safety of intravenous ganciclovir for the treatment of peripheral cytomegalovirus (CMV) retinitis in patients with AIDS. Patients were randomly assigned to receive either immediate treatment, intravenous ganciclovir, 5 mg/kg twice daily for 14 days followed by 5 mg/kg once daily for 14 weeks, or deferred treatment. Patients randomized to deferred treatment whose retinitis progressed were offered ganciclovir. Of the 22 patients randomized to deferred treatment who were included in the final analysis, 20 were found to have progressive CMV retinitis compared with 10 of the 13 randomized to immediate treatment. The median time to progression in the deferred treatment group, as determined by a masked fundus photography reading center, was 13.5 days compared with 49.5 days in the immediate treatment group (mean +/- SD, 19.3 +/- 4.1 vs. 66.4 +/- 14.0; P = .001, log rank test). These data indicate that ganciclovir delays the progression of CMV peripheral retinitis in persons with AIDS.

Prevalence of resistance in patients receiving ganciclovir for serious cytomegalovirus infection.

Seventy-two AIDS patients treated with ganciclovir for cytomegalovirus (CMV) disease were prospectively monitored for the development of drug-resistant virus. No resistant strains were found in 31 patients before therapy or among seven culture-positive patients treated for less than or equal to 3 months. Of 13 culture-positive patients treated for greater than or equal to 3 months, 5 excreted virus resistant (ED50, greater than 12 microM, or ED90, greater than 30 microM) to ganciclovir. Thus, 38% of patients and receiving ganciclovir for greater than 3 months and excreting virus or, overall, 7.6% of the patients were excreting CMV resistant to the drug.