Gentamicin and tobramycin Kinetics.

Eighty-two hospitalized adult patients were randomized to treatment with gentamicin or tobramycin. Serum levels were compared to computer-derived mathematically predicted levels to evaluate predictability of gentamicin and tobramycin serum levels. When comparable dosages were used mean peak gentamicin levels (4.87 micrograms/ml) did not differ from those after tobramycin (4.31 micrograms/ml). Seventy-three percent of patients had peak levels after gentamicin greater than 4.0 micrograms/ml compared to 46% after tobramycin. Factors purported to influence predictability of aminoglycoside serum levels were examined. In 46 of 74 patients whose actual body weight was 10 to 35 kg less than estimated ideal body weight levels after both drugs were lower than predicted. Serum levels were also lower than predicted in 7 of 11 patients with ascites, 6 of 7 patients receiving carbenicillin therapy, and 17 of 29 patients who had pneumonia. Neither hematocrit nor temperature appeared to influence predictability of serum levels. A comparison of methods used to obtain computer-derived predicted levels showed that ideal body weight provided the most accurate prediction. Differences between predicted and measured levels were established when calculations were based on actual body weight (P = 0.009) or on surface area (P = 0.003 for peak and 0.023 for trough levels).

Waterborne typhoid fever in Dade County, Florida. Clinical and therapeutic evaluation of 105 bacteremic patients.

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.

Prophylaxis of infection in patients with aplastic anemia receiving allogeneic marrow transplants.

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.

The effect of prophylactic intravenous immune globulin on the incidence of septicemia in marrow transplant recipients.

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.

APIC and the 1985 position paper: "Listen to the music".

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.

Stratified outcome comparison of clindamycin-gentamicin vs chloramphenicol-gentamicin for treatment of intra-abdominal sepsis.

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.

Cefoxitin: its role in treatment and prophylaxis of obstetric and gynecologic infections.

Cefoxitin has become one of the most used parenteral antibiotics in the United States, perhaps because of a broad spectrum of activity, including activity against Bacteroides fragilis, which makes the drug suitable for prevention and treatment of intraabdominal and pelvic infections. This review focuses on the use of cefoxitin in obstetric and gynecologic infections, with comparisons to older and newer antibiotics. Numerous studies have shown that cefoxitin is clearly effective; in most of these studies, however, either the initial infection rates were low or the sample sizes were small--circumstances making it difficult to establish the superiority of any one agent. Thus, the necessity of using a drug with activity against B. fragilis for prevention and treatment of pelvic infections has not been proven. Several antibiotics without such activity have been equally effective. Cefoxitin may be of particular value when combined with surgical drainage of pelvic abscesses, infections in which control of B. fragilis may be especially important to outcome.

Antibacterial activity of a new parenteral cephalosporin--HR 756: comparison with cefamandole and ceforanide.

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.

Orthopedic infections: A prospective study of 378 clean procedures.

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.

Screening for cross-reacting capsular polysaccharide K antigens of Escherichia coli using antiserum agar.

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.

Acute renal infection in women: treatment with trimethoprim-sulfamethoxazole or ampicillin for two or six weeks. A randomized trial.

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.

In vitro comparison of dibekacin and gentamicin activities.

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.

Intracardiac infections due to coagulase-negative Staphylococcus associated with Hickman catheters.

Three bone marrow transplant recipients experienced right-sided intracardiac infection due to coagulase-negative Staphylococcus infection associated with Hickman catheter use. In each case, multiple blood cultures yielded coagulase-negative Staphylococcus organisms, and echocardiography demonstrated mass lesions or vegetations in the right atrium. Two patients appeared to have infected intracardiac thrombi without definite valvular involvement, whereas one had both an atrial mass and a tricuspid valve vegetation. All patients were treated with catheter removal and 4 weeks of antibiotic therapy, and one patient required cardiac surgery after failure of antibiotic therapy and an apparent paradoxic embolus to the central nervous system. Intracardiac infection is a rare but potentially fatal complication of Hickman catheter use. Echocardiography may be useful in establishing the diagnosis in suspected cases.

Infectious complications of marrow transplant: risk factors for infection.

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.

Cefazaflur, a new parenteral cephalosporin: in vitro studies.

Cefazaflur was tested in vitro against 262 strains of bacteria. Inhibitory and bactericidal concentrations were determined with two inoculum sizes of bacterial cells in Mueller-Hinton broth and nutrient broth. Agar dilution studies also were performed. When tested in agar, 5.0 mug or less of cefazaflur per ml inhibited almost all strains of Staphylococcus aureus, Escherichia coli, Klebsiella, and Proteus mirabilis. The drug was less active against Enterobacter and indole-positive Proteus, and 7.5 mug of antibiotic per ml inhibited approximately two-thirds to one-fourth of the strains. A concentration of 50 mug of cefazaflur per ml was required for inhibition of the enterococci. There was negligible activity against Pseudomonas. The drug demonstrated less activity in broth than in agar, and a major inoculum effect was seen with some strains. For example, with a lower inoculum, 2.5 mug of cefazaflur per ml killed all strains of E. coli, whereas with the higher inoculum, 7.5 mug of cefazaflur per ml, inhibited 64% and killed only 8% of strains. The activity of the drug for some strains was greater in Mueller-Hinton broth; for others, it was greater in nutrient broth. There were considerable differences in the results of the broth and agar studies for some species when the same medium was employed. Because of differences in activity found with different media, inocula, and method of testing, an evaluation of the eventual usefulness of cefazaflur must await the results of in vivo studies.

Comparative in vitro activity of the new oral cephalosporin cefixime.

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.