Sequential antibiotic therapy: Effective cost management and patient care.

The escalating costs associated with antimicrobial chemotherapy have become of increasing concern to physicians, pharmacists and patients alike. A number of strategies have been developed to address this problem. This article focuses specifically on sequential antibiotic therapy (sat), which is the strategy of converting patients from intravenous to oral medication regardless of whether the same or a different class of drug is used. Advantages of sat include economic benefits, patient benefits and benefits to the health care provider. Potential disadvantages are cost to the consumer and the risk of therapeutic failure. A critical review of the published literature shows that evidence from randomized controlled trials supports the role of sat. However, it is also clear that further studies are necessary to determine the optimal time for intravenous to oral changeover and to identify the variables that may interfere with the use of oral drugs. Procedures necessary for the implementation of a sat program in the hospital setting are also discussed.

Cefotetan: a second-generation cephalosporin active against anaerobic bacteria. Committee on Antimicrobial Agents, Canadian Infectious Disease Society.

OBJECTIVE: To offer guidelines for the use of cefotetan, a cephamycin antibiotic, in order to minimize its overprescription. OPTIONS: Clinical practice options considered were treatment of infections with the use of second- and third-generation cephalosporins, carbapenems such as imipenem as well as combination regimens of agents active against anaerobic bacteria, such as metronidazole or clindamycin with an aminoglycoside. OUTCOMES: In order of importance: efficacy, side effects and cost. EVIDENCE: A MEDLINE search of articles published between January 1982 and December 1993. In-vitro and pharmacokinetic studies published in recognized peer-reviewed journals that used recognized standard methods with appropriate controls were reviewed. For results of clinical trials, the reviewers emphasized randomized double-blind trials with appropriate controls. VALUES: The Antimicrobial Agents Committee of the Canadian Infectious Disease Society (CIDS) and a recognized expert (M.J.G.) recommended use of cefotetan to prevent and treat infections against which it has proved effective in randomized controlled trials. BENEFITS, HARMS AND COSTS: These guidelines should lead to less inappropriate prescribing of cefotetan, with its attendant costs and risk of development of resistant bacteria. RECOMMENDATIONS: Cefotetan could be considered an alternative single agent for prophylaxis of infection in patients undergoing elective bowel surgery. It may be used to treat patients with acute pelvic inflammatory disease and endometritis. VALIDATION: This article was prepared, reviewed and revised by the Committee on Antimicrobial Agents of the CIDS. It was then reviewed by the Council of the CIDS, and any further necessary revisions were made by the chairman of the committee.

The diagnosis and significance of bacteriuria in people with spinal cord injury.

Quantitative urine cultures are used to identify individuals in whom urine in the bladder is not sterile, that is, those who have bacteriuria. In people with spinal cord injury the criteria which best distinguish specimen contamination from bacteriuria have been established, and are lower than the traditional ≥1055 CFU/ml criterion. Bacteriuria mayor may not be symptomatic, and the benefits of treatment mayor may not outweigh the risks.Abnormal levels of pyuria are present in the great majority of spinal cord injured people who have indwelling catheters or who use intermittent catheterization. In the latter group, catheter urine is not homogeneous, and levels of pyuria are highest in the terminal fraction of catheter urine. Absence of pyuria is a good indicator of absence of high count gram negative bacteriuria, but pyuria may be present in the absence of bacteriuria in this population. No methods suitable for routine clinical use are currently available to localize the site of urinary infection in this population.Frequently recurrent or persistent bacteriuria is extremely common in people with spinal cord injury. Bacteriuria is most often asymptomatic, yet is clearly significant in that it is responsible for measurable short-term and long-term morbidity. However, at present, quantitative urine cultures and tests for pyuria cannot, by themselves, be used to identify spinal cord injured persons who will reliably benefit from treatment for bacteriuria.

Histologically proven pressure sore-related osteomyelitis in the setting of negative technetium bone scans. Case report.

Pressure sores are common in patients with spinal cord injury, stroke or debilitating medical illness. Contiguous osteomyelitis is a well recognized complication of pressure ulcers, but remains a challenging diagnostic and management problem. Technetium bone scan is purported to be an extremely sensitive, although nonspecific diagnostic test for osteomyelitis. Indeed, a negative bone scan is thought to virtually exclude bone infection. We report three cases of pressure sore-related polymicrobial osteomyelitis where technetium bone scan was normal, yet bone biopsy demonstrated characteristic histopathologic changes of osteomyelitis. These cases raise questions regarding the sensitivity of bone scanning in the setting of pressure sores, and they demonstrate the need for further investigation into the correlation between nuclear medicine scan results and bone biopsy histopathology. Bone biopsy remains the gold standard for diagnosis of osteomyelitis, which can be present in bone underlying a pressure ulcer, even in the setting of a normal bone scan.

Prophylaxis of urinary tract infection in persons with recent spinal cord injury: a prospective, randomized, double-blind, placebo-controlled study of trimethoprim-sulfamethoxazole.

PURPOSE: To determine the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) for prophylaxis of urinary tract infection in persons with recent spinal cord injury, during the first 4 months of intermittent catheterization. PATIENTS AND METHODS: One hundred twenty-nine adults (112 men, 17 women) with recent acute spinal cord injury participated in a randomized, double-blind, placebo-controlled trial, and were studied for up to 16 weeks. Low-dose TMP-SMX (TMP 40 mg, SMX 200 mg) or placebo was given once daily. Clinical observations, urine cultures, and cultures of rectal and urethral swabs were made weekly. Subjects who developed breakthrough bacteriuria received conventional antimicrobial therapy and prophylaxis was continued. RESULTS: Sixty-six TMP-SMX recipients (57 men, 9 women) and 60 placebo recipients (52 men, 8 women) are evaluable for efficacy. Among male subjects, bacteriuria was present during 50% or more of study weeks in 30% of TMP-SMX recipients and in 56% of placebo recipients (p = 0.003). The interval to the onset of bacteriuria was prolonged in TMP-SMX recipients (p < 0.0001). TMP-SMX recipients without bacteriuria in any given week had a lower probability of having bacteriuria the subsequent week (0.26) than did placebo recipients (0.49) (p < 0.0001). At least 1 episode of definite symptomatic bacteriuria (bacteriuria and fever and at least 1 classical manifestation of urinary infection) occurred in 4 of 57 TMP-SMX-treated men and in 18 of 52 placebo-treated men (p < 0.0003). We observed similar trends in women, but differences did not reach statistical significance, perhaps because the number of females was small. Adverse events suspected to be due to medications were frequent in this population of patients with recent severe injuries and led to discontinuation of the study in 10% of the TMP-SMX group and 8% of the placebo group. Adverse events included neutropenia (TMP-SMX: two; placebo: three), pseudomembranous colitis (TMP-SMX: one), severe skin rash (TMP-SMX: two; placebo: one), and drug fever (TMP-SMX: one). The proportion of all episodes of bacteriuria that were due to TMP-SMX-resistant organisms was unexpectedly high in the placebo group (51%), and increased progressively according to year of enrollment in the study. By Year 3, all subjects in the placebo group had at least one episode of TMP-SMX-resistant bacteriuria. Gram-negative enteric bacilli resistant to TMP-SMX were recovered from rectal swabs (TMP-SMX 49%, placebo 42%) and urethral swabs (TMP-SMX 33%, placebo 26%) in similar proportions of subjects in the two study groups. CONCLUSIONS: Prophylaxis with TMP-SMX significantly reduces bacteriuria and symptomatic urinary tract infection in persons with recent acute spinal cord injury during bladder retraining using intermittent catheterization. However, adverse reactions attributable to TMP-SMX are common in this population. Colonization and breakthrough bacteriuria with TMP-SMX-resistant organisms are frequent and may seriously limit the usefulness of this strategy, particularly in an institutional setting.

Pyuria: its relationship to bacteriuria in spinal cord injured patients on intermittent catheterization.

Observations made during a study of intermittently catheterized spinal cord injured patients suggested that leukocyte counts yield higher results in aliquots of terminal-catheter urine (TCU) than in midstream-catheter urine (MCU) or suprapubic aspirate (SPA). The purpose of this study was to confirm that observation, to examine the relationship of leukocyte counts in TCU, MCU, and SPA to the leukocyte excretion rate (LER), and of pyuria to bacteriuria in this population. We collected sets of urine specimens obtained by SPA and intermittent catheterization (for leukocyte counts and quantitative culture) and timed urine collections (for LER determination). Fifty-two patients were studied for an average of five days. Leukocyte counts were performed in 241 SPA, 250 MCU, and 236 TCU specimens, and LER in 131 timed collections. The mean of the logarithm of leukocyte counts differed significantly between TCU and both MCU and SPA (p less than .0001). The difference between TCU and MCU was greater than 150 leukocytes/mm3 for 25% of paired specimens (mean 624 leukocytes/mm3, median 15 leukocytes/mm3). The statistical correlation between LER and leukocyte counts in all catheter specimens was significant; however, SPA and MCU frequently underestimated LER and TCU overestimated LER. Estimates of pyuria do not clearly separate bacteriuric from abacteriuric specimens. In spinal cord injured patients on intermittent catheterization, aliquots of catheter urine are not suitable for estimation of pyuria, and estimation of pyuria is not a feasible screening test for bacteriuria.

Evaluation of diagnostic criteria for bacteriuria in acutely spinal cord injured patients undergoing intermittent catheterization.

To evaluate diagnostic criteria for bacteriuria in acutely spinal cord injured patients undergoing intermittent catheterization, we studied paired urine specimens obtained by suprapubic aspiration and intermittent catheterization. Culture of suprapubic aspirate was used to define presence or absence of bacteriuria. Fifty patients were studied for an average of 5 consecutive days; bacteriuria occurred within the study period in 47 (94%). Low-level bacteriuria was frequent; thus, the traditional diagnostic criterion, greater than or equal to 10(5) cfu/ml of midcatheter urine, had unacceptably low sensitivity (gram-positive organisms 0.45; gram-negative organisms 0.65) for bacteriuria documented by suprapubic aspiration. The best diagnostic criterion for gram-positive bacteriuria was between greater than or equal to 10(1) cfu/ml (sensitivity 0.91, specificity 0.86) and greater than or equal to 10(2) cfu/ml (sensitivity 0.85, specificity 0.93). For gram-negative bacteriuria, greater than or equal to 10(1) cfu/ml was optimal (sensitivity 0.96, specificity 0.96); a more practical criterion, greater than or equal to 10(2) cfu/ml, retained excellent sensitivity (0.91). Suprapubic or flank pain and/or tenderness occurred in five of 47 bacteriuric subjects; nonspecific symptoms, possibly associated with bacteriuria, were seen in an additional 28 subjects. We conclude that, in this unique population, a criterion of greater than or equal to 10(2) cfu/ml of midcatheter urine should be used for diagnosis of bacteriuria.

Hemophilus aphrophilus vertebral osteomyelitis: a case report and literature review.

We report a 60-yr-old diabetic female who developed vertebral osteomyelitis and discitis due to Hemophilus aphrophilus, and review three previously reported cases of this uncommon infection. Predisposing factors, clinical features, and treatment of H. aphrophilus vertebral osteomyelitis are discussed.

Clostridium difficile in Crohn's disease.

Clostridium difficile has been detected in the stools of some patients with relapse of Crohn's disease. The authors looked prospectively for present or previous exposure to C. difficile cytotoxin in 10 patients with mild to severe Crohn's disease. None of 25 stool samples from these 10 patients was positive for C. difficile cytotoxin. These negative stool ultrafiltrates had mild cytotoxin neutralizing activity, but this finding did not differ from that in 30 cytotoxin-negative stools from patients with other diarrheal diseases. Serum from these patients also showed no cytotoxin neutralizing activity. Review of the literature reveals that C. difficile can cause complications ranging from diarrhea to toxic megacolon in a small but variable proportion of patients with Crohn's disease. There is no evidence that C. difficile plays a part in the pathogenesis of the disease.

Prospective randomized trial of piperacillin monotherapy versus carboxypenicillin-aminoglycoside combination regimens in the empirical treatment of serious bacterial infections.

Piperacillin as a single agent was compared in a prospective randomized trial with carboxypenicillin-aminoglycoside combinations in empirical therapy of serious bacterial infections. The difference in the clinical response rates with piperacillin (77% of 26 infection episodes) and combination therapy (75% of 24 infection episodes) were not statistically significant. Fewer adverse effects occurred in the piperacillin-treated group (42%) than in the combination-treated group (71%) (P = 0.0399 by Fisher's exact test), although neither nephrotoxicity nor hypokalemia alone was significantly less frequent in patients receiving piperacillin. However, the emergence of resistant organisms during therapy was more frequent among patients receiving piperacillin alone (42% of patients) than among patients receiving combination therapy (17% of patients) (P = 0.465 by Fisher's exact test). Moreover, emergence of resistance accounted for 5 of 9 patients with treatment failure, superinfection, or both when piperacillin was used as a single agent, compared with 2 of 10 similar patients in the combination group (P = 0.1299 by Fisher's exact test). The use of piperacillin as a single agent in the treatment of serious bacterial infections is not advocated, and the addition of an aminoglycoside to prevent emergence of resistance during empirical therapy of such infections is strongly recommended.

Characterization of the hemolytic activity of Staphylococcus aureus strains associated with toxic shock syndrome.

The hemolytic activity of 32 vaginal isolates of Staphylococcus aureus from patients with typical toxic shock syndrome (TSS) was contrasted with that of 50 vaginal isolates from patients without TSS, using a standardized inoculum (10(5) CFU) on 5% sheep blood agar after 48 h of incubation under 30% CO2. Additionally, 7 nongenital isolates from patients with nonmenstrual TSS and 57 strains of nongenital control isolates were included for comparison. Vaginal TSS strains were significantly less hemolytic than non-TSS S. aureus strains of either genital (P less than 0.001) or nongenital (P less than 0.01) origin. Vaginal TSS S. aureus strains were also less hemolytic than were nongenital TSS S. aureus strains (P less than 0.02). This reduced hemolytic activity of genital TSS S. aureus strains may provide a useful marker for screening and further delineation of toxigenic S. aureus associated with menstrually related TSS.

Campylobacter infections in pregnancy. Case report and literature review.

Campylobacter fetus is a major cause of venereally transmitted abortion and sterility in ungulates, and a recently recognized, common enteric pathogen in man. The role of the organism as a cause of human fetal wastage has not been delineated. We present a case of bacteremic campylobacter infection in a pregnant woman, and review the published cases of campylobacteriosis in pregnancy and the perinatal period. Systemic maternal infection may present either as prolonged febrile illness or fulminant sepsis, and transplacental spread may result in abortion, stillbirth, or early neonatal meningitis. Enteritis that occurs in infants born to women with campylobacter diarrhea may represent fecal-oral spread at or near the time of delivery. With improved microbiologic techniques and greater awareness by physicians, the prevalence and importance of campylobacteriosis in pregnancy should become better appreciated.