Antimicrobial prophylaxis in surgery.
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Biomedical subjects
Publications and source records attributed to A R Ronald.
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Multiresistant strains of Haemophilus ducreyi, the aetiological agent of chancroid, are prevalent in Nairobi, Kenya, where tetracyclines and sulphonamides are no longer very effective in the treatment of chancroid. The following regimens (given three times daily for seven days) were compared in a double-blind randomised trial--amoxycillin 500 mg, amoxycillin 500 mg and clavulanic acid 125 mg, and amoxycillin 500 mg and clavulanic acid 250 mg. 68 of 100 ulcers were culture-positive for H. ducreyi. All strains of H. ducreyi produced beta-lactamase. At day 7 none of the amoxycillin-treated patients had responded clinically or bacteriologically, whereas all but 2 of 56 patients treated with an amoxycillin/clavulanic-acid regimen had responded clinically and H. ducreyi had been eradicated from their ulcers. The combination of amoxycillin-clavulanic acid appears to be very effective for the treatment of chancroid. The results of this study accord with H. ducreyi as the primary pathogen of chancroid.
One hundred seventeen unselected women with symptoms of acute cystitis were randomized to groups for immediate therapy with one of the following four single-dose regimens: (1) 1 g of sulfisoxazole; (2) 2 g of sulfisoxazole; (3) a combination of trimethoprim, 160 mg, and sulfamethoxazole, 800 mg; and (4) a combination of trimethoprim, 320 mg, and sulfamethoxazole, 1,600 mg. Forty-one women were excluded, 13 did not return for follow-up, and 28 did not have significant bacteriuria in the pretherapy culture. Escherichia coli was isolated in 81% of infections. Antibacterial activity was significantly greater in urine collected during the 24 hours after therapy in those who received trimethoprim-sulfamethoxazole. However, overall cure varied from 85% to 95%, without any great differences between the regimens. The rate of cure of 69% in the 13 patients with presumptive evidence of renal infection (antibody-coated bacteria present) was significantly lower than the rate of cure of 95% in women without evidence of renal infection. Single-dose therapy with these regimens was safe and effective in adult women with symptoms of acute cystitis, regardless of the localization of the site of infection.
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To assess the significance of sexual intercourse as a precipitating factor of urinary tract infection in premenopausal women with recurrent infection, 15 patients were monitored with daily dipslides and calendar recording of intercourse episodes after antimicrobial prophylaxis was discontinued. Eleven patients experienced 16 infections; 12 infections occurred within 24 hr of an intercourse episode, two occurred during the menstrual period, and two had no recognizable association. In 12 control subjects, followed in a similar fashion, three infections--all within 24 hr of an intercourse episode--were documented. There was no difference in frequency of intercourse between patients and controls, but the frequency was higher in infected women than in uninfected women (P less than 0.02). These data suggest that in sexually active women, most urinary tract infections are intercourse-related.
Rifampin susceptibility of nasopharyngeal Haemophilus influenzae strains was determined before and after community-wide chemoprophylaxis with rifampin (children) and sequential minocycline-rifampin (adults). All strains were rifampin susceptible before prophylaxis, but 10.3% of the strains at 1 week and 7.5% of the strains at 9 weeks after prophylaxis were rifampin resistant.
A survey was made of the frequency of resistance to amikacin, gentamicin and tobramycin among aerobic gram-negative bacilli isolated over a 4-week period in 1979 at six large, geographically separated Canadian hospitals. In the entire series of 4407 isolates the frequency of resistance was 2.5% to amikacin, 8.1% to gentamicin, 5.9% to tobramycin and 1.7% to all three. Most (81%) of the resistant bacteria were acquired by the patients after admission to hospital. The frequency of resistance to the three aminoglycoside antibiotics in each hospital largely reflected the local rate of cross-infection by endemic strains of resistant bacteria.
Trimethoprim was used alone to treat urinary tract infections in 20 women who were unable to tolerate sulfonamides. Of ten acute symptomatic urinary tract infections, four were cured, three were not, and three cases could not be evaluated. Two other women received trimethoprim for suppression of infection complicating stag-horn calculi. The conditions of both patients improved clinically but the urine remained infected. Eight women treated prophylactically with low-dose trimethoprim for recurrent urinary tract infection accumulated a total of 16 patient-years of prophylaxis. During treatment, the incidence of infection was 0.56 per patient-year compared with 4.25 infections in the year preceding study. Adverse reactions occurred in eight of 20 patients and administration of the drug had to be stopped in five cases. Trimethoprim alone is effective for the treatment and prophylaxis of urinary tract infections, but may cause a high incidence of adverse reactions in patients known to be sensitive to sulfonamides.
Eighty-one women were randomly selected for treatment with nalidixic acid (1 g four times a day) or cephalexin (500 mg four times a day) as therapy for 131 episodes of bacteriuria localized using the antibody-coated bacteria (ACB) test. Bladder infections were treated for three days and renal infections for 14 days. Rates of cure were not significantly different between treatment groups in each drug regimen. However, significantly more relapses occurred in the patients with ACB-positive infections treated for 14 days with cephalexin than in those treated for 14 days with nalidixic acid. More early reinfections occurred in the cephalexin-treated group after both three and 14 days of therapy. Resistance to nalidixic acid developed in the infecting bacteria in the urine during therapy with nalidixic acid in 3% of women after three days and in 16% of women after 14 days. Simultaneous resistance appeared in the urine, periurethral area, and fecal flora of these patients.
Twenty women with recurrent or persistent urinary tract infections were treated with a fixed combination of trimethoprim-rifampin (TMP-RAM). The site of infection was established by the antibody-coated bacteria test. Sixteen women had upper tract infections (antibody-coated bacteria tests positive); eight were cured, three failed, and five relapsed. All four women with lower tract infections (antibody-coated bacteria tests negative) were cured. Three of five patients with structural abnormalities failed. The 12 cures and 5 relapses were associated with organisms susceptible to either TMP (minimal inhibitory concentration, less than or = to 7 micrograms/ml) or RAM (minimal inhibitory concentration, less than or = to 32 micrograms/ml). In contrast, two of the three failures were associated with organisms resistant to both TMP and RAM. In one patient, RAM resistance emerged during treatment. During therapy, urinary strains were eradicated from the periurethral and anal-canal areas in all but 3 fo 16 patients. Adverse reactions, noted in 16 women, included nausea (10), dizziness (6), headaches (2), rash (1), an blurred vision (1). Antimicrobial susceptibility data on 246 isolated from urinary, periurethral, and anal-canal specimens are included. Our findings suggest that TMP-RAM is effective in urinary infections and may prevent the emergence of RAM-resistant strains.
The susceptibility of 47 strains of Haemophilus ducreyi to amoxicillin, clavulanic acid, and the combination of both drugs was determined by agar dilution susceptibility testing. A synergistic antibacterial activity of the combination was found for beta-lactamase-producing strains.
A peripheral leukocyte migration inhibition test has been used to demonstrate cellular immunity to a protein component of Neisseria gonorrhoeae. Human leukocytes served as effector cells in an agarose method to distinguish antigen-sensitive from nonsensitive individuals. Leukocytes, preincubated with antigen, were placed in wells in medium 199 agarose. After 18 h of incubation the migration index was calculated by dividing the area of migration of cells preincubated with antigen by the area of migration of the control cells. Significant migration inhibition was demonstrated for 16 of the 30 patients with uncomplicated gonorrhoea. Maximum inhibition was obtained 7-10 days following the onset of symptoms and the duration of the response varied from 14 to more than 40 days. There was a statistically significant positive correlation between the number of previous infections and migration inhibition. A control group, which included individuals with Neisseria meningitidis infection, showed an insignificant response to this gonococcal antigen. Although these results indicate the presence of cell-mediated immunity, the significance of this response in the protection of the host or in the pathogenesis of gonococcal disease has yet to be determined.
For a period of one year we identified all urinary isolates of Enterobacteriaceae resistant to either nalidixic acid (NA) or trimethoprim (TMP). Host and organism characteristics associated with the occurrence of 68 NA and 61 TMP-resistant isolates were compared with 61 matched antimicrobial-susceptible controls. Minimum inhibitory concentrations to NA and TMP were carried out on all isolates, Escherichia coli isolates were biotyped and TMP-sulfamethoxazole (SMX) synergy studies were performed on TMP-resistant isolates. Study patients were reviewed with regard to age, renal function, presence of structural urinary tract abnormality, history of antimicrobial treatment and persistence of study strains within the urinary tract. Resistance to both drugs was associated with prior treatment with the relevant antimicrobial and with underlying urinary tract abnormality. No association was noted between resistance and patient age or renal function. Once resistant organisms infected an abnormal urinary tract, they were able to persist almost indefinitely. Patients with persistent urinary infections associated with structural urinary tract abnormality account for most NA or TMP-resistant infections in our hospital and constitute an identifiable group in whom the therapeutic usefulness of these drugs is limited.
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Careful animal studies have demonstrated the scientific rationale for perioperative antimicrobial therapy in selected operations in order to prevent infectious complications. Operative procedures that carry increased risk for the patients or in which the results of infection are devastating, should now be carried out concomitantly with antimicrobial prophylaxis. Several studies have shown that therapy must begin before bacteria can establish themselves in the operative field and need not be continued for more than 24 hours. These principles should now be implemented in surgical practice with careful ongoing surveillance of infection, incidence and antimicrobial use to ensure their continuing efficacy.
The results of a prospective, randomized comparative study of the efficacy and toxicity of clindamycin, chloramphenicol, and ticarcillin in the treatment, concomitantly with gentamicin to ensure complete aerobic coverage, of 175 patients with serious mixed aerobic/anaerobic intraabdominal or female genital tract sepsis are reported. In the group with intraabdominal sepsis, 33 (79%) of 42 treated with clindamycin, 43 (81%) of 53 treated with chloramphenicol, and 35 (90%) of 39 treated with ticarcillin were cured. In the group with genital tract sepsis, 16 (94%) of 17 treated with clindamycin, 11 (100%) of 11 treated with chloramphenicol, and 12 (92%) of 13 treated with ticarcillin were cured. Diarrhea occurred most frequently in patients treated with clindamycin (P < 0.001), hematologic suppression occurred most frequently in patients treated with chloramphenicol (P < 0.01), and hypokalemia occurred most frequently in patients treated with ticarcillin (P < 0.01). Clindamycin, chloramphenicol, and ticarcillin, each in combination with gentamicin, are equally effective in therapy for intraabdominal or female genital tract sepsis.
Introital colonization with Enterobacteriaceae is considered to be one of the principal predisposing factors to recurrent urinary tract infections (UTI) in adult females. One proposed mechanism allowing introital colonization in these patients is the absence of local cervicovaginal antibody. To test this hypothesis, we examined cervicovaginal washings from 22 patients with a history of recurrent UTI and 29 normal controls with no history of UTI for specific local antibody by using indirect immunofluorescence. No significant difference in antibody was found in these populations. Fourteen percent (3/22) of the patients had antibody to their introital Escherichia coli and 34% (10/29) of the controls had antibody to their fecal E. coli. Consequently, a sensitive radioimmunoassay technique was developed to detect cervicovaginal antibody. A solid phase was prepared by coupling to Sepharose 4B a pool of eight serogroups of E. coli which are frequently implicated in UTI. Serial dilutions of cervicovaginal washings were reacted with the solid phase, and the absorbed anti-E. coli antibodies were detected by the uptake of (125)I-labeled anti-human immunoglobulin G (IgG) or anti-human IgA. The antibody levels were quantitated by interpolation on a standard curve prepared by using immunospecifically purified human anti-E. coli antibodies. IgG and IgA levels were measured in washings from 10 colonized patients, 13 non-colonized patients, and 12 controls. There were no significant differences in IgG and IgA levels in cervicovaginal washings among the three groups. In these studies, introital colonization was not related to cervicovaginal antibody.
The diagnosis of bacterial urinary infections is reasonably exact and routine in medical practice. In contrast, therapeutic regimens have been arbitrary with little rationale and no relationship to infection site or therapeutic objective. During the past decades a series of careful prospective studies have carefully characterized episodes of infection to the site within the urinary tract, and adequate follow-up has been obtained to determine the pattern of response. This has led to the emergence of definite guidelines on dose and duration for antimicrobial therapy. The antimicrobial combination of trimethoprim and sulfamethoxazole has been employed in many of these studies and has been found to be a particularly effective agent for both the treatment and prevention of urinary infections. These studies and their implications for optimal treatment of urinary infections are reviewed.