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PURPOSE Hematopoietic cell transplantation can cure hematologic malignancies and other diseases, but this treatment can also cause late complications. Previous studies have evaluated the cumulative effects of late complications on survival, but longer-term effects on life expectancy after hematopoietic cell transplantation have not been assessed. PATIENTS AND METHODS We used standard methods to evaluate mortality, projected life expectancy, and causes of death in a cohort of 2,574 patients who survived without recurrence of the original disease for at least 5 years after allogeneic or autologous hematopoietic cell transplantation from 1970 through 2002. Sex- and age-specific comparisons were made with US population data. Results Estimated survival of the cohort at 20 years after transplantation was 80.4% (95% CI, 78.1% to 82.6%). During 22,923 person-years of follow-up, 357 deaths occurred. Mortality rates remained four- to nine-fold higher than the expected population rate for at least 30 years after transplantation, yielding an estimated 30% lower life expectancy compared with that in the general population, regardless of current age. In rank order, the leading causes of excess deaths were second malignancies and recurrent disease, followed by infections, chronic graft-versus-host disease, respiratory diseases, and cardiovascular diseases. CONCLUSION Patients who have survived for at least 5 years after hematopoietic cell transplantation without recurrence of the original disease have a high probability of surviving for an additional 15 years, but life expectancy is not fully restored. Further effort is needed to reduce the burden of disease and treatment-related complications in this population.

Objective: The purpose of this study was to analyze enrollment of racial/ethnic minorities in Phase I and Phase II HIV vaccine trials in the U.S. conducted by National Institute of Allergy and Infectious Diseases (NIAID)-funded networks from 1988 to 2002., Methods: A centralized database was searched for all NIAID-funded networks of HIV vaccine trial enrollment data in the U.S. from 1988 through 2002. The authors reviewed data from Phase I or Phase II preventive HIV vaccine trials that included HIV-1 uninfected participants at low to moderate or high risk for HIV infection based on self-reported risk behaviors. Of 66 identified trials, 55 (52 Phase I, 3 Phase II) met selection criteria and were used for analyses. Investigators extracted data on participant demographics using statistical software., Results: A total of 3,731 volunteers enrolled in U.S. NIAID-funded network HIV vaccine trials from 1988 to 2002. Racial/ethnic minority participants represented 17% of the overall enrollment. By pooling data across all NIAID-funded networks from 1988 to 2002, the proportion of racial/ethnic minority participants was significantly greater (Fisher's exact test p-value < 0.001) in Phase II trials (278/1,061 or 26%) than in Phase I trials (347/2,670 or 13%). By generalized estimating equations, the proportion of minorities in Phase I trials increased over time (p = 0.017), indicating a significant increase in racial/ethnic minority participants from 1988 to 2002., Conclusions: There has been a gradual increase in racial/ethnic minority participation in NIAID-funded network HIV vaccine trials in the U.S. since 1988. In the light of recent efficacy trial results, it is essential to continue to increase the enrollment of diverse populations in HIV vaccine research.

Objectives: We estimated the number and cost of syphilis-attributable HIV cases among African Americans., Methods: A mathematical model of HIV transmission was used to estimate the number of partnerships consisting of HIV-discordant African Americans in which infectious syphilis was present and the number of new HIV cases attributable to syphilis in these partnerships., Results: In 2000, an estimated 545 new cases of HIV infection among African Americans could be attributed to the facilitative effects of infectious syphilis, at a cost of about 113 million dollars., Conclusions: Syphilis prevention could reduce HIV incidence rates and the disproportionate burden of HIV/AIDS on the African American community, resulting in substantial reductions in future HIV/AIDS medical costs.

Of 1506 marrow transplant patients from 1980 through 1986 reviewed for risk factors for invasive candidal infection defined by positive blood cultures, biopsy, or histologic evidence of tissue invasion, 171 (11.4%) had invasive infection, with a significantly higher incidence in the more recent years of review; 40% (69 patients) had evidence of tissue-invasive disease without fungemia. Of 102 patients with fungemia, 45% had candidemia alone with a mortality of 39%. Mortality in patients with tissue involvement was 90% with or without fungemia. Factors that increased infection were age, acute graft-versus-host disease, and donor mismatch. Factors that decreased infection included conditioning with 12 Gy of fractionated irradiation and cyclophosphamide, transplantation for aplastic anemia, and more rapid engraftment. Among fungemic patients, the number of days of fungemia was a risk factor for tissue invasion while more rapid engraftment was protective.

Background: Graft-versus-host disease (GVHD) and infection are major complications of allogeneic bone marrow transplantation. Since intravenous immunoglobulin has shown benefit in several immunodeficiency and autoimmune disorders, we studied its antimicrobial and immunomodulatory role after marrow transplantation., Methods: In a randomized trial of 382 patients, transplant recipients given immunoglobulin (500 mg per kilogram of body weight weekly to day 90, then monthly to day 360 after transplantation) were compared with controls not given immunoglobulin. By chance, the immunoglobulin group included more patients with advanced-stage neoplasms; otherwise, the study groups were balanced for prognostic factors., Results: Control patients seronegative for cytomegalovirus who received seronegative blood products remained seronegative, but seronegative patients who received immunoglobulin and screened blood had a passive transfer of cytomegalovirus antibody (median titer, 1:64). Among the 61 seronegative patients who could be evaluated, none contracted interstitial pneumonia; among the 308 seropositive patients evaluated, 22 percent of control patients and 13 percent of immunoglobulin recipients had this complication (P = 0.021). Control patients had an increased risk of gram-negative septicemia (relative risk = 2.65, P = 0.0039) and local infection (relative risk = 1.36, P = 0.029) and received 51 more units of platelets than did immunoglobulin recipients. Neither survival nor the risk of relapse was altered by immunoglobulin. However, among patients greater than or equal to 20 years old, there was a reduction in the incidence of acute GVHD (51 percent in controls vs. 34 percent in immunoglobulin recipients; P = 0.0051) and a decrease in deaths due to transplant-related causes after transplantation of HLA-identical marrow (46 percent vs. 30 percent; P = 0.023)., Conclusions: Passive immunotherapy with intravenous immunoglobulin decreases the risk of acute GVHD, associated interstitial pneumonia, and infections after bone marrow transplantation.

Nineteen patients with phaeohyphomycosis were treated with itraconazole. Of these, 17 were assessable for clinical outcome. Of these, two had received no prior therapy, five had failed amphotericin B therapy, four had failed ketoconazole or miconazole therapy, and five had failed both amphotericin B and azole therapy. One patient had received only prior surgical intervention. Fungi of seven different genera caused disease of the skin in nine patients, soft tissue in nine, sinuses in eight, bone in five, joints in two, and lungs in two. Itraconazole was given in dosages ranging from 50 to 600 mg/day for 1 to 48 months. Clinical improvement or remission occurred in nine patients. Two patients have had stabilization of disease. Six patients failed treatment, one had a relapse after initially successful treatment. Itraconazole appears to be highly effective in some patients with phaeohyphomycosis, including patients refractory to other antifungal agents.

A prospective, double-blind, placebo-controlled study was conducted to determine the safety and efficacy of endotracheal tobramycin (ETT) for treatment of gram-negative bacterial pneumonia. Patients were randomized to either 40 mg of tobramycin or a placebo instilled endotracheally every 8 h. Patients also received intravenous tobramycin plus either cefazolin or piperacillin. Of 85 patients enrolled, 41 were assessable. Most microbiologic diagnoses were made by endotracheal aspiration with strict grading criteria. The clinical-radiographic responses of patients and standard demographic data were recorded. Pseudomonas aeruginosa, "multiple pathogens," and Klebsiella-Enterobacter-Serratia-Citrobacter species were isolated in 41, 32, and 15% of the instances, respectively. Causative pathogens were eradicated from sputum significantly more frequently by patients who received ETT (P less than 0.05). However, no significant differences were noted in the clinical outcomes of the two study groups. No local adverse reactions attributable to the administration of this agent were observed, but four patients had supraventricular tachycardia, compared with none who received the placebo (P = 0.053). ETT may be considered as adjunctive therapy for seriously ill individuals.

In 1975 an outbreak of group A meningococcal disease began in Seattle, Washington, and cases subsequently were recognized throughout the Pacific Northwest. Nearly one-half of the affected persons were Native Americans; two-thirds were alcohol abusers and/or habitués of skid road communities. In Seattle, group A meningococci colonized asymptomatic persons only if these individuals had contact with skid road (P = .006). The epidemic strain may have spread from American Indians in Manitoba, Canada. Traditional migration routes connect the two populations; asymptomatic American Indians on reservations in Washington carried group A meningococci. Vaccination programs were undertaken in four cities but only after cases occurred. In Seattle, vaccination reached 80% of the target population and was associated with a significant decrease in incidence of the disease, but cases recurred after the program ended. The social habits of skid road communities, combined with the "case-triggering" approach to, and premature termination of, vaccination programs, may have resulted in 56% of regional cases occurring after the start of the vaccination program in Seattle.

One hundred one patients with severe aplastic anemia underwent allogeneic marrow transplantation and received one of three forms of infection prophylaxis: oral nonabsorbable antibiotics and isolation and decontamination in a laminar airflow room (36 patients); prophylactic granulocyte transfusions from a single family member donor (33 patients); or conventional treatment in single rooms with hand-washing and mask precautions (31 patients). During the period of granulocytopenia, patients in the laminar airflow rooms acquired fewer infections than either of the other groups, but this difference was statistically significant only when compared with the group receiving conventional treatment. Patients in the laminar airflow rooms had significantly fewer infections after engraftment as compared with the other two groups. Incidence of interstitial pneumonia and graft rejection was not different among the three groups. Acute graft-versus-host disease occurred later (Day 47) in the group in the laminar airflow rooms as compared with the group receiving prophylactic granulocyte transfusions (Day 23) or the group receiving conventional treatment (Day 20). The incidence of grades II to IV acute graft-versus-host disease was less in the patients in the laminar airflow rooms but only reached borderline significance (p = 0.08) when compared with the conventionally treated patients. The survival at Day 100 was 92 percent for the group in the laminar airflow rooms, 79 percent for the group receiving prophylactic granulocyte transfusions, and 64 percent for the group receiving conventional treatment.

One hundred twelve patients with hematologic malignancies underwent marrow transplantation from HLA-matched sibling donors and were randomized to receive either prophylactic granulocyte transfusions (PG, 67 patients) or prophylactic systemic antibiotics (PSA, 45 patients) as prophylaxis against nosocomial infections. Patients were treated in conventional hospital rooms and studied until day 100 post-transplant. For the entire study period, 26 patients (39%) in the PG group developed septicemia compared to 15 patients (33%) in the PSA group. Twenty-eight patients (42%) in the PG group developed local major infections compared to 19 patients (42%) in the PSA group. Ten patients (15%) in the PG group developed viral interstitial pneumonitis compared to 6 patients (13%) in the PSA group. None of these differences were statistically significant. There was no difference in the incidence of bacterial or fungal infections or viral interstitial pneumonitis between the two groups during the granulocytopenic or post-engraftment period. There was no difference in the incidence and severity of graft-versus-host-disease (GVHD). Inability to carry out the prophylaxis was frequent in the PG group, with complications necessitating discontinuance of transfusion in 24% of the recipients and 13% of the donors. The use of PG as an infection prophylaxis modality in marrow transplantation is not supported by this study, as it is difficult to carry out and because PG did not show any advantage over the use of PSA in preventing nosocomial infections.

We reevaluated conventional criteria for diagnosing coliform infection of the lower urinary tract in symptomatic women by obtaining cultures of the urethra, vagina, midstream urine, and bladder urine. The traditional diagnostic criterion, greater than or equal to 10(5) bacteria per milliliter of midstream urine, identified only 51 per cent of women whose bladder urine contained coliformis. We found the best diagnostic criterion to be greater than or equal to 10(2) bacteria per milliliter (sensitivity, 0.95; specificity, 0.85). Although isolation of less than 10(5) coliforms per milliliter of midstream urine has had a low predictive value of previous studies of asymptomatic women, the predictive value of the criterion of greater than or equal to 10(2) per milliliter was high (0.88) among symptomatic women the prevalence of coliform infection exceeded 50 per cent. In view of these findings, clinicians and microbiologists should alter their approach to the diagnosis and treatment of women with acute symptomatic coliform infection of the lower urinary tract.

An immunofluorescent-antibody test was developed for rapid detection of Pseudomonas aeruginosa in blood cultures. The test uses a murine monoclonal antibody specific for all strains of P. aeruginosa. In initial tests, bright uniform immunofluorescence signals were seen when each of the 17 international serotypes, as well as 14 additional isolates of P. aeruginosa, were examined. No immunofluorescent staining was observed when 37 other gram-negative and 15 gram-positive species were studied. In a clinical study, the assay was applied to broth smears of 86 gram-negative bacilli isolated from 74 bacteremic patients and 28 additional clinical isolates of Pseudomonas sp. and other oxidase-positive gram-negative bacilli recovered from various body sites. Smears were made directly from blood cultures which were positive for gram-negative bacilli by Gram staining. Eleven (15%) of 74 patients with gram-negative bacteremia had a positive test for P. aeruginosa. Including the results of these 11 isolates recovered in a prospective study and an additional 10 isolates from a retrospective study, we obtained a sensitivity and specificity of 100% (21 positive specimens and 103 negative specimens, respectively). These preliminary results suggest that this is a useful reagent for rapid presumptive identification of P. aeruginosa in blood cultures. With the immunofluorescent-antibody test, P. aeruginosa could be identified within 1 h of Gram stain evidence of gram-negative bacteremia.

Dibekacin, a new parenteral aminoglycoside, was compared with gentamicin in vitro against 221 clinical isolates. Tests for minimum inhibitory concentrations, performed in agar, demonstrated that dibekacin was comparable to gentamicin against most isolates tested. Dibekacin was slightly more active than gentamicin against some isolates of Pseudomonas aeruginosa, but was significantly less active against strains of Serratia.

An extensive outbreak of waterborne typhoid fever occurred in 1973 at a migrant labor camp in Dade County, Florida. Blood cultures from 105 of the 188 patients with proved or presumptive cases of typhoid fever grew Salmonella typhi. The clinical and laboratory findings in these patients were reviewed. Fever, usually with temperatures above 38.8 degrees C and of the sustained type, was a primary manifestation of disease, although a majority of the patients also complained of headache and gastroenteric symptoms. Hepatic or splenic enlargement was present in 52 per cent and 42 per cent, respectively, whereas rose spots were detected in only 13 per cent. The total leukocyte count was normal in 74 per cent, but serum levels of liver and muscle enzymes were frequently elevated. Gastrointestinal, pulmonary and neurologic complications were infrequent; circulatory failure was not observed. Defervescence in response to antibiotic therapy was variable; however, the median response among 68 patients who received chloramphenicol was two days less than that in 34 patients treated with ampicillin. There was one possible treatment failure with ampicillin. The relapse rate of 10 per cent in chloramphenicol-treated patients was not significantly greater than the 3 per cent rate among those treated with ampicillin. Serologic studies for typhoid fever were of limited diagnostic value since the titer of agglutinins was 1:160 or higher in 49 per cent of the serums obtained before treatment, and a fourfold rise in titer occurred in only 24 per cent of 57 patients studied. The serologic response to chloramphenicol treatment did not differ from that to ampicillin.

Interviews conducted during outbreaks of group A meningococcal disease in skid row communities suggested that heavy alcohol use was associated with increased risk of disease. Frequent moving within skid row and from one skid row to another was characteristic of a subpopulation with increased risk of disease and may have facilitated spread within and between skid rows. The observations discussed herein have important implications for control of communicable diseases in and near skid rows.

The efficacy of a single dose (four tablets) and of 10-day courses of trimethoprim-sulfamethoxazole (TMP-SMZ) was studied in 77 women with symptomatic cystitis and negative tests for antibody-coated bacteria. Cure rates after six weeks were 76% for single-dose therapy and 87% for 10 days of treatment. For Escherichia coli infections, cure rates after six weeks were 80% and 86%, respectively. However, 10-day treatment eliminated enteric bacilli from urethral and vaginal sites more often than did single-dose therapy. Two weeks after completion of treatment, perineal colonization was observed more often in the women who developed recurrent infections than in those who did not (P = 0.01). During these two weeks, recurrent infections were found somewhat more often in the women who had received single-dose therapy than in those who had undergone 10-day treatment (5 of 38 vs. 2 of 39; P = 0.07). With conventional courses of antibiotics, retreatment of all recurrent infections was less successful in women previously given single-dose therapy. Recurrent infections were also more frequent in women infected with bacteria other than E. coli. Both drug regimens were well tolerated. However, serious adverse reactions were fewer in patients treated with a single dose (8.5%) than in patients treated for 10 days (15%). Single-dose therapy with TMP-SMZ appears as effective as 10-day therapy in acute uncomplicated cystitis caused by E. coli.

To study once-daily antimicrobial prophylaxis of urinary tract infections, we gave trimethoprim-sulfamethoxazole (40 mg/200 mg), trimethoprim (100 mg), nitrofurantoin macrocrystals (100 mg), or placebo to 60 women for 6 months. During prophylaxis, infections per patient year were comparable in the groups receiving trimethoprim (0.0), nitrofurantoin (0.14), or trimethoprim-sulfamethoxazole (0.15) and occurred less frequently than in patients receiving placebo (2.8; P less than 0.001, placebo versus each drug regimen). The effectiveness of prophylaxis was limited to the 6 months that antimicrobials were given, and infections were more likely to develop after prophylaxis in women who had three or more infections in the year before prophylaxis (P less than 0.005). Further, women whose preprophylaxis infection was positive for antibody-coated bacteria were more likely to have same-strain relapse when infections recurred (P = 0.001). Emergence of trimethoprim-resistant Escherichia coli was rare, but non-E. coli infections occurred more often after prophylaxis (P less than 0.05). Prophylaxis with these drugs is effective, well tolerated, and did not produce emergence of resistant E. coli but may predispose to non-E. coli urinary tract infections after its discontinuation.

An orthopedic surgeon in whom hepatitis B subsequently developed participated in operations on 49 patients in the two months preceding his illness. Thirty of these patients were available for subsequent clinical and serologic follow-up: five had positive reactions for antibody to hepatitis B surface antigen (anti-HBs) and one had a positive reaction for hepatitis B surface antigen (HBsAg) at the initial examination an average of 77 days after surgery. No new patients had either clinical or serologic evidence of hepatitis B during four months of subsequent follow-up (mean of 6.7 months after surgery). A control group of 56 orthopedic patients had a 25% prevalence of positive reactions for anti-HBs and negative reactions for HBsAg- this was not significantly different from the exposed group. The risk to patients of acquiring hepatitis B after surgical exposure in this setting from a surgeon is low.

The Association for Practitioners in Infection Control (APIC), in existence now for 16 years, is still considered to be a relatively young professional organization. During that time its many accomplishments include membership growth to more than 7500 persons, establishment of a national office, annual revenues of more than $700,000, publications of a bimonthly scientific journal, publication of the standard reference work for infection control practice, establishment of the process leading to a certifying examination in infection control, an annual educational conference attended by more than 1000 persons, and increasing recognition by other professional groups, state and federal agencies, and the scientific community as a leading voice that represents professionals involved in infection control practice in the United States. These accomplishments have been due in large part to the dedication and hard work of its members, especially the hundreds of persons who have filled local and national positions of leadership. However, APIC now finds itself at a crossroads; changes in the current health care climate and publication of the results of a national study on the efficacy of infection control practice have contributed to a reassessment of infection control programs and the role and scope of persons involved in the field. The purpose of this editorial is to review the background of our two position papers, to comment on an expanded role of hospital epidemiology, and to examine the response of APIC to our membership in terms of commitments identified in the two papers.

The effect of delay in processing on results of lysis-centrifugation (LC; Isolator) blood cultures was assessed in 4,577 paired blood specimens. Blood specimens were obtained at all hours from 384 febrile marrow transplant patients with indwelling venous catheters and were processed by the LC technique and by a conventional two-bottle method. Most patients (84%) were receiving broad-spectrum antibiotics at the time of blood culture. Specimens were delivered to the laboratory, where Isolator tubes were held at 35 degrees C and processed in batches between 0700 and 1730 h daily. This procedure resulted in a delay beyond the manufacturer-suggested processing time of less than 8 h for 1,853 (42%) of the LC cultures. There was no overall difference in the recovery of organisms present in LC cultures processed after being held for 8 to 24 h compared with the conventional two-bottle method. LC methodology had shorter time to detection than the conventional method for detection of Candida spp. and Pseudomonas spp. (P less than 0.05). However, time to detection for Streptococcus spp. and members of the family Enterobacteriaceae, responsible for 16.3% of total isolates, was prolonged significantly by delay in processing when compared with the conventional two-bottle method (P less than 0.01). Results of this study support the recommendation of the manufacturer for processing of Isolator tubes within 8 h or less. Although one can safely delay processing beyond 8 h in terms of total recovery of organisms, such delays were associated with longer time to detection for certain important potentially pathogenic organisms which accounted for a sizeable proportion of blood culture isolates from marrow transplant patients.

99 patients with hematological malignancies underwent allogeneic marrow transplantation from HLA-identical sibling donors and were randomized to receive one of two forms of infection prophylaxis while granulocytopenic: (1) prophylactic systemic antibiotics in a conventional hospital room (PSA, 50 patients) or (2) decontamination, isolation in a laminar air flow room and the administration of prophylactic systemic antibiotics (LAF + PSA, 49 patients). Only 1 patient (3%) in the LAF + PSA group acquired septicemia while granulocytopenic compared to 11 (24%) patients in the PSA group (p less than 0.005). Three patients (6%) in the LAF + PSA group acquired major localized infections compared to 9 (18%) in the PSA group (p = 0.06). There was no significant difference in days in hospital post transplant, days of granulocytopenia, days of fever, incidence of acute graft-versus-host disease, interstitial pneumonitis or overall survival. We conclude that the use of prophylactic systemic antibiotics added to decontamination and laminar air flow isolation of patients undergoing marrow transplantation significantly reduces the incidence of septicemia in the granulocytopenic period.

We evaluated the in vitro synergistic activity at clinically attainable concentrations of combinations of aminoglycoside and beta-lactam antibiotics against 30 gentamicin-resistant clinical isolates of gram-negative bacilli. All 56 pairs of 4 aminoglycosides and 14 beta-lactams were evaluated. Combinations with amikacin demonstrated inhibitory synergistic activity in 29% of the assays, as compared with 22% for netilmicin (P = 0.018), 17% for gentamicin (P less than 0.001), and 13% for tobramycin (P less than 0.001). Among the beta-lactams, combinations with cefoperazone, ceftriaxone, or cefpiramide (SM-1652) demonstrated inhibitory synergistic activity most often (39, 38, and 35% of the assays, respectively) and with ceforanide, cefsulodin, and imipenem least often (less than or equal to 8% each). The most active combination was amikacin and ceftriaxone, with which 67% of the assays demonstrated inhibitory synergism. Isolates with high-level resistance to either antibiotic in a combination were unlikely to be inhibited synergistically by the combination. Further, combinations generally demonstrated little synergistic activity against isolates highly susceptible to beta-lactams.

The use of prophylactic low-dose penicillin acutely burned, hospitalized patients remains controversial. Fifty-one adult patients with burns of 1% to 91% total body surface area were prospectively studied to determine the efficacy of prophylactic penicillin in the prevention of wound cellulitis and burn wound sepsis, and to examine the influence of prophylactic penicillin on the emergence of antibiotic resistant microorganisms. In 25 patients given a 5-day course of penicillin prophylactically, 11 developed cellulitis and two had burn wound sepsis. A similar group of patients given placebo developed seven cases of cellulitis and three cases of burn wound sepsis (p = 0.340). No patient in either group developed gentamicin-resistant Gram-negative organisms, although the gastrointestinal tracts of two patients in the penicillin group showed new colonization by yeast. We conclude that the routine administration of prophylactic penicillin neither protects against cellulitis and burn wound sepsis, nor promotes selection of antibiotic-resistant bacteria in hospitalized patients with acute thermal injury.

The pharmacokinetic properties of cyclacillin administered as a 3.0-g oral dose, with and without progenecid, have been studied and correlated with in vitro activity of the drug against 109 isolates of Neisseria gonorrhoeae. By 8 h after dosage, levels of cyclacillin in serum declined below the minimal inhibitory concentration and the inferior antibacterial activity of cyclacillin (compared with that of amipicillin) suggest that cyclacillin is not a promising alternative to ampicillin for single-dose treatment of gonorrhea.

Cefoxitin is active in vitro against beta-lactamase-producing strains of Neisseria gonorrhoeae; therefore, its efficacy in the treatment of uncomplicated genital gonorrhea was evaluated in a study of ten men and 15 women. Cefoxitin was administered in two intramuscular doses given 5 hr apart, patients alternately receiving either 1 g or 2 g of cefoxitin in each injection. Probenecid (1 g) was administered orally with both injections to five women, and with the first injection only in the remaining patients. All cases of gonococcal cervicitis or urethritis were cured, and all rectal carriage was eliminated. Four of seven patients had persistent oropharyngeal carriage after treatment. There was no discernible difference between the efficacies of the 1-g and 2-g regimens. It was concluded that the cefoxitin regimens used are effective for therapy of uncomplicated genital or anorectal gonorrhea, but not for eradication of oropharyngeal carriage of N. gonorrhoeae.

Ninety-seven patients randomized to receive (45 patients) or not to receive (52 patients) intravenous cytomegalovirus immune globulin before and after allogeneic marrow transplantation were evaluated retrospectively for the occurrence of bacterial and fungal septicemia in the first 100 days post-transplant. In a proportional hazards regression test, infection prevention regimens, immunoglobulin administration, age and occurrence of acute graft-versus-host disease were tested simultaneously for the occurrence of septicemia in the pre- and post-engraftment period. Of these factors, only patients receiving immunoglobulin had significantly fewer episodes of septicemia following engraftment with 11 (26%) patients in the globulin group having 14 episodes compared to 22 (42%) patients in the control group having 27 episodes (p = 0.039). None of the patients experienced complications with the immunoglobulin infusions. These results suggest that the administration of intravenous immunoglobulin may be a practical and effective method to decrease the incidence of septicemia following marrow transplantation.

A new medium (XT80) containing trimethoprim-sulfamethoxazole (TMP-SMZ) was characterized and compared with kanamycin-containing tryptic soy agar (KA) for the recovery of multiply resistant organisms (MRO) in rectal and stool cultures. Cultures from 151 patients hospitalized for bone marrow transplantation were screened for MRO. A total of 366 MRO were recovered from 702 cultures on 94 patients during a 6-month period. XT80 detected more gram-negative bacilli and Corynebacterium spp. than KA. Detection of Staphylococcus spp. was equivalent for the two media. Multiple-antibiotic resistance, defined as resistance to three or more classes of antibiotics, was confirmed by standard agar disk diffusion susceptibility testing. Growth on XT80 correctly identified heteroresistant strains of methicillin-resistant Staphylococcus spp. XT80 more rapidly detected thymidine-dependent mutants of Staphylococcus spp. and members of the family Enterobacteriaceae. Lipophilic Corynebacterium spp., including Corynebacterium group JK, also were more readily detected with XT80. TMP-SMZ given as prophylaxis against Pneumocystis carinii infection exerts a selective pressure on organisms that colonize immunocompromised patients and appears to select for colonization with MRO. Colonization with MRO preceded infection for 94% of 36 patients who developed bacteremia. XT80 is a useful screening tool; growth on this medium correlates closely with resistance to TMP-SMZ and is as accurate a predictor as KA for the carriage of MRO.

We compared the efficacy of orally administered ampicillin, 2 g/d, with that of trimethoprim-sulfamethoxazole, 320 mg/d-1600 mg/d, given for 2 or 6 weeks for outpatient management of acute uncomplicated renal infection in women. Of 98 women participating in the trial, 60 had renal infections with susceptible strains, complied with drug therapy, and completed 6 weeks of follow-up. Before treatment, 39 women had symptoms and signs of acute pyelonephritis; 21 had symptoms of cystitis but positive tests for antibody-coated bacteria. All 60 women had alleviation of symptoms and resolution of bacteriuria after 7 days of therapy. Subsequent recurrences occurred in 12 of 27 women given ampicillin, compared with 4 of 33 given trimethoprim-sulfamethoxazole (p = 0.008). Serotyping showed that most recurrences were reinfections with ampicillin-resistant strains. With each drug, a 2-week regimen of therapy proved as efficacious as a 6-week regimen, but the longer regimen was less well tolerated. We conclude that a 2-week treatment regimen is sufficient to manage acute pyelonephritis in outpatients and that trimethoprim-sulfamethoxazole is preferable to ampicillin therapy.

122 patients with hematologic malignancies underwent allogeneic marrow transplantation from HLA-matched sibling donors and received one of two forms of infection prophylaxis while granulocytopenic: 1) decontamination and laminar air flow isolation (LAF, 68 patients), and 2) LAF plus prophylactic systemic antibiotics (LAF + PSA, 54 patients). Patients were evaluated for infection acquisition while in isolation. Septicemia occurred in 11 (16%) of the patients in the LAF group and in three (6%) patients in the LAF + PSA group. Fourteen (21%) of the patients in the LAF group and four (7%) patients in the LAF + PSA group had a major local infection. There was no difference in the incidence and severity of graft-versus-host disease or incidence and duration of fever. The addition of prophylactic intravenous broad-spectrum antibiotics for patients isolated in LAF rooms significantly decreased infection acquisition.

Agar plates containing antiserum against group B meningococcus or Haemophilus influenzae type b were used to determine the prevalence of cross-reacting K1 and K100 capsular polysaccharide antigens in 265 isolates of disease-causing Escherichia coli. K1 antigen was found in 22% of isolates from various sites. K100 antigen was found in only three isolates. This technique is a convenient method to detect specific E. coli K antigens for evaluation as possible factors important in the virulence of the organism.

A randomized, prospective trial was conducted of 93 patients with operatively confirmed intra-abdominal sepsis. The study compared clindamycin-gentamicin and chloramphenicol-gentamicin for treatment of carefully stratified patient groups. Malnutrition, age over 65 years, shock, alcoholism, gastrointestinal tract bleeding, steroid administration, diabetes, obesity, and organ malfunction were present with equal frequencies in each group. The duration of antibiotic treatment averaged 8 1/2 days, and the average length of postoperative hospitalization was 29 days. Study antibiotics were changed for bacteriologic reasons in 11 patients taking clindamycin-gentamicin and 12 patients taking chloramphenicol-gentamicin (25% of the total), and two patients in the clindamycin-gentamicin group had a minor adverse reaction. Initial satisfactory clinical responses were obtained in 59 (63%) patients. Twenty-five patients (27%) subsequently developed unsatisfactory courses, but 48 (52%) patients remained well through the 30-day period. Septic-related mortality occurred in 18 (19%) patients, and two (2%) patients had unrelated deaths. There were no significant differences between the study regimens by the outcome criteria evaluated.

Severe infection is a predictable accompaniment of marrow transplant. Advances in therapy for bacterial and some viral infections have reduced the impact of these infections. In contrast, infection due to fungi continue to play a major and even increasing role. The relationship between GVHD and infection is poorly understood, although it is clear that GVHD (and perhaps its treatment) has a major influence on the acquisition and outcome of infection. Advances in the prevention and treatment of GVHD will undoubtedly have parallel benefits in the prevention of infection after marrow transplant.

A Corynebacterium species consistently resistant to all antibiotic therapy except vancomycin caused bacteremia in 32 of 284 (11%) marrow transplant patients. Twenty-one patients had colonization or infection before bacteremia. Twenty-six of the 32 patients were males, and males older than 16 years were infected significantly more often than females over 16, or than all patient under 16. A case-control study showed that infected patients had greater exposure to antibiotics; more often had failure of engraftment and persistent granulocytopenia; were in laminar air-flow rooms less often; and had greater inhospital mortality. Cultural surveillance showed that 17 of 42 marrow transplant patients were colonized with Corynebacterium species. Likelihood of colonization appeared related to age, sex, and duration of hospitalization. Prevalence of colonization in other populations was 1% in nonhospitalized healthy adults and 13% in adults in a general hospital. Corynebacterium species infections occur primarily in adult males with granulocytopenia, mucocutaneous defects, and receiving intensive antibiotic therapy.

Six hundred twenty orthopedic surgery patients were evaluated in a prospective study of postoperative infection. The wound infection rate among the 378 elective clean procedures was 5.8 per cent (3.2 per cent major plus 2.6 per cent minor infections). Staphylococcus aureus was the single most common pathogen recovered in both major and minor infections. Gram-negative rods predominated in major infections, but were rarely found in minor infections. In the clean procedure group, infection rates increased with age and duration of operation. Preoperative consideration should be given to all A "profile sheet" or checklist of several such factors is presented for this purpose.

To determine the cause of the acute urethral syndrome, we studied 59 women with dysuria and frequent urination without "significant bacteriuria" (defined as greater than or equal to 10(5) organisms per milliliter), 35 women with typical cystitis and 66 women with no symptoms of urinary-tract infection. Although none of the 59 women with urethral syndrome had greater than 3.4 x 10(4) bacteria per milliliter in either of two successive midstream urine specimens, samples of bladder urine obtained by suprapubic aspiration or catheterization from 24 women contained coliforms, and samples from three contained Staphylococcus saprophyticus; all but one of these 27 women also had pyuria. Of the 32 women with sterile bladder urine, 10 of 16 with pyuria and one of 16 without pyuria were infected with Chlamydia trachomatis (P = 0.002). Chlamydial infection was found in 11 of 42 women with urethral syndrome and pyuria, in three of 66 without symptoms, and in one of 35 with cystitis (P less than 0.01 when the group with urethral syndrome is compared with either of the other groups). Thus, 42 of 59 women with urethral syndrome had abnormal pyuria and 37 of these 42 were infected with coliforms, S. saprophyticus, or C. trachomatis, whereas few women without pyuria had demonstrable infection. Bacteriuria of greater than or equal to 10(5) per milliliter may be an insensitive diagnostic criterion when applied to symptomatic lower-urinary-tract infection.

One hundred forty-two strains of Escherichia coli isolated from extraintestinal infections were examined for colicin V (ColV) and hemolysin (Hly) production. For comparison, 20 strains isolated from the feces of normal individuals and 12 enteropathogenic strains of E. coli were tested for these properties. Thirty-five to 59% of extraintestinal isolates were Hly+, but only one fecal strain was Hly+. Colicin V biosynthesis was found for 12% of blood culture isolates, 7% of urine culture isolates and 16% of the strains from other extraintestinal infections. None of the fecal isolates was ColV+. Selected strains were tested for virulence in 13-day-old chicken embryos; these same strains were tested for their ability to hemagglutinate chicken or human erythrocytes. Of 22 extraintestinal isolates, 13 (59%) killed greater than or equal to 60% of the embryos within 72 h. Only one of eight normal fecal isolates and two of three enteropathogenic strains tested were virulent. About 80% of the virulent strains were Hly+. The most striking finding, however, was the hemagglutination of human erythrocytes by virulent extraintestinal isolates. It seems possible that the hemagglutination property reflects a specific common adherence factor.

Cefixime was 8 to 10 times more active than cefaclor and augmentin against isolates of Escherichia coli, Klebsiella pneumoniae and Salmonella typhi, MIC90 values ranging from 0.06 to 0.25 micrograms/ml. However, none of these three drugs was particularly active against isolates of more resistant gram-negative bacilli such as Enterobacter, Serratia, Citrobacter, Acinetobacter, Providencia and Achromobacter spp. The lowest MIC values for gram-negative bacilli were seen with ciprofloxacin, except for isolates of Acinetobacter, where cotrimoxazole was the most active of the five drugs studied. Augmentin and ciprofloxacin exhibited the lowest MICs for isolates of streptococci and corynebacteria. Although cefixime may be among the most active oral beta-lactam drugs, it does not appear to be useful for treatment of infections caused by more resistant gram-negative bacilli.

During outbreaks of group A meningococcal disease in Seattle, Wash., and Portland, Oreg., we studied the mucosal flora of the affected population and comparison groups to identify possible determinants of susceptibility and resistance to disease. Antimeningococcal immunoglobulin A can block the bactericidal activity of specific antibodies of other classes and has been associated with susceptibility in adults. We used immunoprecipitation and fluorescent-antibody techniques to detect mucosal microorganisms cross-reactive with group A meningococci that might have stimulated such antibodies. Cross-reactive strains of Bacillus pumilus and Streptococcus faecalis were found. Bacterial interference on mucosal surfaces has been shown to reduce susceptibility to other pathogens. With an agar overlay technique, we sought nasopharyngeal microorganisms that inhibited the growth of group A meningococci. Forty-five percent of subjects carried inhibitory strains representing at least nine different species. Inhibitory strains were less common (32%) in residents from "skid row" areas (see D.J. Bogue, Skid Row in American Cities, University of Chicago Press, for a comprehensive definition of these areas) than in a comparison group that did not experience meningococcal disease (61%), suggesting that their presence may be associated with resistance to acquisition of meningococci or to meningococcal disease.

HR 756, a new parenteral cephalosporin that is beta-lactamase resistant, was tested against 271 bacterial isolates. Both agar and broth dilution testing were employed, using two media and two inoculum sizes of bacteria. Antibacterial activity of the drug was compared to that of cefamandole (CFM) and ceforanide (CFN). In agar, HR 756 was more active than CFM and CFN against all bacteria tested except isolates of Staphylococcus aureus, which were better inhibited by CFM. HR 756 exhibited some antipseudomonas activity in agar, although a marked inoculum effect was apparent. A comparison of median minimum inhibitory and bactericidal concentrations in broth showed again that HR 756 was the most active of these three drugs. HR 756 demonstrated enhanced antibacterial activity compared to CFM and CFN against bacteria sensitive to all three drugs as well as against more resistant isolates of Serratia marcescens, Enterobacter species, and indole-positive Proteus. As with other cephalosporins, results for most bacteria were affected by inoculum size, medium, and type of dilution test employed in in vitro studies.