A clinical risk index for Clostridium difficile infection in hospitalised patients receiving broad-spectrum antibiotics.

Identification of a population at high risk for Clostridium difficile infection (CDI) would enable CDI prevention strategies to be designed. The purpose of this study was to create a clinical risk index that would predict those at risk for CDI. A CDI risk index was therefore developed, based on a cohort of hospital patients given broad-spectrum antibiotics, and divided into a development and validation cohort. Logistic regression equations helped identify significant predictors of CDI. A scoring algorithm for CDI risk was created using identified risk factors and collapsed to create four categories of CDI risk. The area under the receiver operating characteristic (aROC) curve was used to measure goodness-of-fit. Among 54 226 patients, 392 tested positive for C. difficile. Age 50-80 years [odds ratio (OR: 0.5; P<0.0116)], age >80 years (OR: 2.5; P<0.0001), haemodialysis (OR: 1.5; P=0.0227), non-surgical admission (OR: 2.2; P<0.0001) and increasing length of stay in the intensive care unit (OR: 2.1; P<0.0001) were significantly associated with CDI. A simple risk index using presence of significant variables was significantly associated with increasing risk for CDI in both development (OR: 3.57; P<0.001; aROC: 0.733) and validation (OR: 3.31; P<0.001; aROC: 0.712) cohorts. An OR-derived risk index did not perform as well as the simple risk index. This easily implemented risk index should allow stratification of patients into risk group categories for development of CDI and help fashion preventive strategies.

Disseminated histoplasmosis manifesting as a soft-tissue chest wall mass in a heart transplant recipient.

Soft-tissue masses are rarely associated with Histoplasma capsulatum infection. We describe a heart transplant patient who presented with a large right-sided chest wall mass as a manifestation of disseminated histoplasmosis. A successful clinical outcome was achieved upon recognition of the fungal pathogen.

Skin test and blastogenic responses to Sporotrichun schenckii.

In vivo skin testing and in vitro lymphocyte blastogenesis were evaluated in a young adult population as methods for detecting cellular immunity to Sporotrichum schenckii. Similar procedures for Candida albicans and Coccidioides immitis were also investigated. 5 of 143 subjects had positive skin tests and 14 had positive blastogenic responses to S. schenckii. These 14 subjects also exhibited unusually high responses to C. albicans in vitro and 11 of the 14 were female. Data demonstrated a correlation coefficient of 0.89 when comparing the blastogenic assays for S. schenckii and C. albicans, suggesting cross antigenicity. Intact cellular immune mechanisms in combination with exposure to C. albicans may protect the host from systemic infection with S. schenckii. Although a limited number of subjects were studied, as a group, females had more vigorous cellular immune responses to C. albicans than males. The rare occurence of sporothrix infection in females as compared to males may be the result of antigenic stimulation from commonly observed vaginal colonization with C. albicans. The present data indirectly support this hypothesis.

Prevalence of AmpC over-expression in bloodstream isolates of Pseudomonas aeruginosa.

This study examined the contribution of AmpC over-expression to beta-lactam resistance in clinical isolates of Pseudomonas aeruginosa obtained from a hospital in Houston, TX, USA. Seventy-six non-repeat bloodstream isolates obtained during 2003 were screened for ceftazidime resistance in the presence and absence of clavulanic acid 4 mg/L. AmpC was identified by isoelectric focusing (with and without cloxacillin inhibition); stable derepression was ascertained phenotypically by a spectrophotometric assay (with and without preceding induction by imipenem) using nitrocefin as the substrate, and was confirmed subsequently by quantitative RT-PCR of the ampC gene. The clonal relatedness of the AmpC-over-expressing isolates was assessed by pulsed-field gel electrophoresis. In addition, the ampC and ampR gene sequences were determined by PCR and sequencing. For comparison, two standard wild-type strains (PAO1 and ATCC 27853) and three multidrug-susceptible isolates were used as controls. AmpC over-expression was confirmed in 14 ceftazidime-resistant isolates (overall prevalence rate, 18.4%), belonging to seven distinct clones. The most prevalent point mutations in ampC were G27D, V205L and G391A. Point mutations in ampR were also detected in eight ceftazidime-resistant isolates. AmpC over-expression appears to be a significant mechanism of beta-lactam resistance in P. aeruginosa. Understanding the prevalence and mechanisms of beta-lactam resistance in P. aeruginosa may guide the choice of empirical therapy for nosocomial infections in hospitals.

Epidemiology and incidence of Clostridium difficile-associated diarrhoea diagnosed upon admission to a university hospital.

Patients with Clostridium difficile-associated diarrhoea (CDAD) may initially develop symptoms in the community and be subsequently diagnosed at hospital admission. At the present time there is no national surveillance system and no standardized case definition of CDAD in the USA, and baseline data on the incidence and epidemiology of CDAD are scarce. The objective of this study was to report the incidence of CDAD at a tertiary care hospital, and to determine the epidemiology of cases diagnosed within 48h of hospital admission, compared with cases of nosocomial CDAD diagnosed 48h or more after hospitalization. The average incidence was 4.0 cases/10 000 patient-days for CDAD on admission and 7.0 cases/10 000 patient-days for nosocomial CDAD. A significant difference was observed in CDAD rates on admission compared with nosocomial CDAD rates (P=0.017), but no differences were observed over time for either rate. Overall, 44% of cases had CDAD on admission and 56% of cases had nosocomial CDAD. Fifty-six (62%) patients with CDAD on admission had been admitted to the same hospital and 24 (27%) had been admitted to another hospital within the previous 90 days. Only eight (9%) patients had not been exposed to any healthcare services in the 90 days preceding hospital admission. A standardized case definition of healthcare-associated CDAD should include previous hospitalizations. Admitting physicians should consider C. difficile in the differential diagnosis of patients admitted with diarrhoea, with or without a history of admission to healthcare facilities.

Risk factors for postoperative chest wound infections due to gram-negative bacteria in cardiac surgery patients.

Gram-negative bacteria account for up to 35% of postoperative sternal wound infections (SWI) in patients undergoing cardiac surgery. Despite this, risk factors for Gram-negative SWI have not been investigated. The objective of this study was to define risk factors associated with Gram-negative SWI in patients undergoing cardiac surgery. 2590 patients undergoing cardiac surgery between 2002-2005 were prospectively monitored for development of SWI. Patient, operative, and post-operative risk factors were compared among patients that developed Gram-negative SWI and Gram-positive SWI to uninfected controls using univariate and multivariate analysis. A p < 0.05 was considered significant. Surgical site infections developed in 152 (5.9%) patients. Isolates were recovered from the sternum for 128 (5.0%) patients, from the leg donor site for 19 (0.73%) patients, and from the sternum and donor site for 5 (0.19%) patients. Gram-positive pathogens were isolated from 83 (3.3%) patients, Gram-negative pathogens from 42 (1.6%) patients, and mixed pathogens from 27 (1.0%) patients. Hospital admission greater than 48 hours before surgery (OR: 2.25; 95% CI: 1.11 - 4.58), ventilator-dependency preoperatively (OR: 5.32 95% CI: 2.22 - 12.75), and thoracentesis procedure postoperatively (OR: 3.71; 95% CI: 1.45 - 9.49) and diabetes (OR: 2.04; 95% CI: 1.17 - 3.55) were identified as significant risk factors for SWI due to Gram-negative bacteria using multivariate logistic regression. Diabetes, increased age, and peripheral vascular disease were identified as significant risk factors for SWI due to Gram-positive bacteria (p < 0.05, each). The risk factors associated with Gram-negative SWI differed significantly from those associated with Gram-positive SWI. Risk factors associated with Gram-negative SWI were identified. Unique interventions may be necessary to prevent Gram-negative SWI in cardiac surgery patients.

Intrarenal abscess. Report of 14 cases.

Six of 14 patients with renal abscess had prior history of urinary tract infection; initial symptoms included fever and flank pain in 12. A drip-infusion intravenous pyelogram was the most sensitive radiologic test, but selective renal arteriography was most specific. Urine cultures were positive in all 14 patients; blood cultures were positive in nine. Six patients were treated with antibiotics alone and eight required surgery. Of the eight, five had pus-filled cavities, one had multiple stones, one had a renal infarct, and one had a resolving abscess. Of six treated with antibiotics alone, one died of unrelated complications and five have demonstrated no pathological renal condition after three to six years.

Oral ciprofloxacin vs parenteral cefotaxime in the treatment of difficult skin and skin structure infections. A multicenter trial.

A prospective, randomized, double-blind, multicenter study was conducted of hospitalized patients to compare the efficacy and safety of oral ciprofloxacin (dosage, 750 mg every 12 hours) with intravenous cefotaxime (dosage, 2.0 g every 8 hours) as monotherapy for difficult skin and skin structure infections requiring hospitalization. Five hundred seventy patients were assessed for an analysis of safety and 461 patients were assessed for an analysis of efficacy. The most common infections were infected ulcers and abscesses. At the end of therapy, there was a higher incidence of recurrent or persistent organisms in the cefotaxime group compared with ciprofloxacin. Adverse reactions related to either therapy were rare. By pathogens, there were no differences in activity, except the higher rate of recurrent or persistent Pseudomonas aeruginosa infection in the cefotaxime group. By diagnosis, the two drugs had comparable efficacy, except for the higher incidence of bacteriologic failure in patients with polymicrobial infected ulcers in the cefotaxime group. Larger studies are needed to evaluate emergence of resistance to ciprofloxacin. Oral ciprofloxacin therapy is as safe and effective as parenteral cefotaxime in the treatment of difficult infections of the skin and skin structure, and affords the prospect of early discharge from the hospital and significant cost savings.

Treatment of skin, skin structure, bone, and joint infections with ceftazidime.

The collective experience with ceftazidime in the treatment of skin, soft tissue, bone, and joint infections is presented. Patients were treated with dosages ranging between 25 and 150 mg/kg per day for between five and 42 days. A total of 570 patients with skin and skin structure infections were treated with ceftazidime. Comparative studies, using either cefamandole or tobramycin plus ticarcillin as control drugs, included 239 patients. There were 600 evaluable patients in five categories of skin or skin structure infection: 252 patients had cellulitis, 107 had wound infections, 103 had abscesses, 90 had skin ulcers, and 48 had other miscellaneous infections. Bacteriologic etiologies were gram-negative rods in 303 episodes, gram-positive cocci in 241, anaerobes in 14 episodes, and miscellaneous other organisms in 48 episodes. Overall bacteriologic efficacy was 90 percent in ceftazidime-treated infections and 76 percent in control-treated infections. The clinical efficacy of ceftazidime against infections caused by the gram-positive cocci, particularly Staphylococcus species, was surprisingly good (85 percent) and similar to the efficacy achieved in the cefamandole-treated patients (85 percent). The overall clinical efficacy for ceftazidime was 93 percent. One hundred thirty-four patients with bone or joint infections received ceftazidime. The dosages were similar, but the duration of treatment was the longest in this group. Ceftazidime treatment was compared with standard dosages of tobramycin and ticarcillin in 11 patients. Osteomyelitis was cured in 58 of the 101 patients who received ceftazidime. In five patients, osteomyelitis failed to respond: in two, a resistant Pseudomonas strain emerged; the other three failures were due to persistent bone sequestra. Thirty-eight patients showed improvement. Of those in the tobramycin and ticarcillin group, nine of 10 evaluable patients (90 percent) showed either cure or improvement. The one failure was due to a persistent sequestrum. Thirteen patients with septic arthritis and seven with bursitis were also treated with ceftazidime; the overall cure rate was 75 percent. Adverse reactions to ceftazidime were severe, and the drug was discontinued in 13 of 570 (2.3 percent) patients with skin or skin structure infections and in five of 134 (3.7 percent) patients with bone and joint infections. These data suggest that ceftazidime is effective as monotherapy in the treatment of skin, skin structure, bone, and joint infections, and that it may be more efficacious against staphylococcal infections than predicted from in vitro data.

Cefotaxime and prophylaxis. New approaches with a proven agent.

Cefotaxime, a third-generation cephalosporin, is active against many troublesome gram-negative organisms and anaerobes that now more frequently cause nosocomial infection. Single-dose cefotaxime, 1 g or 2 g administered 30 minutes prior to surgery, has been proven to be effective as prophylaxis for infection following gastrointestinal, biliary, obstetric, gynecologic, and genito-urinary procedures. When published trials are compiled, single-dose cefotaxime is more effective than multiple-dose cefazolin (p less than 0.01) in these types of surgery. Unfortunately, the dramatic increase in cephalosporin use has been accompanied by the emergence of resistant organisms such as enterococci and fungi. In Europe, some centers successfully prevent nosocomial pneumonia in intubated patients by decontaminating gastric contents with a combination of nonabsorbable antimicrobial agents including cefotaxime. Further trials may validate this concept for use in the United States.

Role for newer beta-lactam antibiotics in treatment of osteomyelitis.

Monotherapy of osteomyelitis with the newer broad-spectrum beta-lactam antibiotics has become attractive because of the efficacy, safety, and cost of these antibiotics when compared with conventional combination therapy. Imipenem/cilastatin is a recent and promising addition to this antibiotic family. Experience with imipenem/cilastatin and that reported for cefotaxime, ceftazidime, and ceftizoxime in the treatment of biopsy-proved osteomyelitis was compared, using data from published reports from five centers. Two hundred forty-three patients were evaluable: 34 were treated with imipenem/cilastatin, 84 with cefotaxime, 122 with ceftazidime, and 33 with ceftizoxime. Staphylococcus aureus was isolated by 80 bone cultures and was the most common single species encountered. There were 75 isolates of Pseudomonas aeruginosa, 113 mixed Enterobacteriaceae species, 115 mixed gram-positive and -negative isolates of miscellaneous species, and 30 anerobic isolates. Polymicrobial infection was present in 101 cases (41.6 percent). Failure rates were similarly low in all groups (10 to 30 percent). However, resistance developed during therapy in all groups with P. aeruginosa. Side effects were predictably few, but reversible neutropenia, pseudomembranous colitis due to Clostridium difficile, and nausea required therapy to be discontinued in seven patients. Imipenem/cilastatin should prove to be a very effective and relatively safe single agent for treatment of osteomyelitis.

Intravenous/oral ciprofloxacin versus intravenous ceftazidime in the treatment of serious gram-negative infections of the skin and skin structure.

A prospective, randomized, non-blind comparison of sequential intravenous/oral ciprofloxacin with parenteral ceftazidime as treatment for serious infections of the skin and skin structure caused by susceptible gram-negative organisms was conducted. For mixed gram-positive or anaerobic infections, concurrent therapy with vancomycin or anti-anaerobic agents was used. The mean duration of therapy was 25 days for the 32 evaluable ciprofloxacin-treated patients and 19 days for the 19 evaluable ceftazidime-treated patients. Overall response was "cure" in 24 of 32 (75 percent) ciprofloxacin-treated patients and 11 of 19 (58 percent) ceftazidime-treated patients (0.01 less than p less than 0.05). Ciprofloxacin eradicated 36 of 46 (78 percent) pathogens and ceftazidime 21 of 29 (72 percent) pathogens. Superinfections occurred in nine of 32 (28 percent) ciprofloxacin patients and in two of 19 (11 percent) ceftazidime patients (0.01 less than p less than 0.05). Adverse reactions requiring cessation of therapy occurred in two of 32 (6 percent) ciprofloxacin patients and in one of 19 (5 percent) ceftazidime patients. There was one death in each group; neither was due to the infection or antimicrobial therapy. Chronic infection was a significant risk factor for failure in both groups. Ciprofloxacin was as effective and safe as ceftazidime for serious infections of the skin and skin structure.

Imipenem/cilastatin in the treatment of osteomyelitis.

Thirty-four patients with osteomyelitis were treated for a mean of 32.5 days with 2 to 4 g per day of imipenem/cilastatin. Twenty-six infections involving the lower extremities were associated with accidents and prosthesis implantation, and 19 of 34 patients had more than one organism isolated. Gram-positive and gram-negative organisms were equally represented, but follow-up bone culture samples showed only 11 percent of gram-positive organisms persisted versus 23 percent of gram-negative organisms. Seventy-four percent of patients were cured or improved, and failures were related to resistant organisms and the inability to perform adequate surgical debridement. Adverse drug side effects included nausea, diarrhea, liver enzyme elevations, and neutropenia, but discontinuation of treatment was required in only three patients. Imipenem/cilastatin holds promise as monotherapy in complicated polymicrobial osteomyelitis.

Ticarcillin plus clavulanic acid (Timentin) therapy for osteomyelitis.

Timentin is an exciting new antibiotic agent that is a combination of ticarcillin and clavulanic acid. Forty-seven patients with osteomyelitis received 3.1 g of Timentin intravenously every six hours. The mean duration of therapy was 32 days. The diagnosis was made by bone biopsy; bone biopsy was repeated at the completion of therapy. The bacterial etiology was predominately gram-positive organisms. Of the organisms isolated, Staphylococcus aureus was the most common isolate and represented 39 percent of the total isolates. Streptococcus species were isolated in 13 percent, Group D Enterococcus in 15 percent, Pseudomonas aeruginosa in 10 percent; 23 percent of the isolates were other gram-negative organisms. All but one organism were initially sensitive to Timentin. Three resistant organisms were isolated during therapy. Twenty-seven patients were classified as having a cure, based on no growth on repeat bone biopsy cultures and clinical signs of bone healing. Twenty-two patients returned for follow-up (one to nine months after therapy) and had no evidence of infection; however, because of the short follow-up period, these patients were classified as showing improvement. Six patients had adverse reactions to Timentin: two had mild allergic phenomena and two had prolonged bleeding times. In all four, therapy was discontinued. Two patients had a transient, mild elevation in the level of serum glutamic-pyruvic transaminase (less than twice normal levels). This new agent looks exciting for therapy of both gram-positive and gram-negative bacterial osteomyelitis.

A comparative evaluation of oral ofloxacin versus intravenous cefotaxime therapy for serious skin and skin structure infections.

In a single-blind, placebo-controlled randomized trial, 100 successive patients were enrolled with serious skin and soft-tissue infections, whose illnesses had precipitated an initial hospital admission or an extension of inpatient care. There were 93 evaluable patients who received either ofloxacin, 400 mg orally every 12 hours plus an intravenously administered placebo every eight hours, or cefotaxime, 2.0 g intravenously every eight hours plus an orally administered placebo every 12 hours. The average length of therapy was 12 days. Both patient groups had similar demographics and underlying conditions. Wound infection was the most common diagnosis, followed by abscess, cellulitis, and trophic ulcer. Multiple pathogens were commonly isolated from infected sites (1.4 pathogens/patient). The most common pathogen was Staphylococcus aureus, followed by Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia marcescens, Proteus/Providencia spp., and Enterobacter spp. Persistence of the initial pathogen at the end of therapy was observed in 22.5 percent of the cefotaxime-treated group, but in only 10 percent of the ofloxacin-treated group. There was one clinical failure in the cefotaxime group, caused by a susceptible strain of Enterobacter cloacae, and there was one clinical failure in the ofloxacin group, in which the patient had an Acinetobacter calcoaceticus var. anitratus wound infection and subsequently developed a P. aeruginosa superinfection. Adverse experiences, including rash, insomnia, and nausea, occurred in 16 percent of the patients in each group. It was concluded that oral ofloxacin is as safe and efficacious as parenteral cefotaxime in the treatment of serious skin and skin structure infections.

Therapy for disseminated coccidioidomycosis with transfer factor from a related donor.

A 17 year old caucasian woman in whom disseminated coccidioidomycosis developed with culture positive meningitis during her third trimester of pregnancy was treated with amphotericin B and subsequently with transfer factor prepared from her father's peripheral lymphocytes. Clinical response and in vivo and in vitro immunologic data indicated that this transfer factor afforded a significant contribution to her survival whereas previous therapy with transfer factor from an unrelated donor provided only transient immunologic reactivity. This experience suggests that transfer factor prepared from a related donor with positive responses to C. immitis may be more efficacious than that prepared from an unrelated donor.

Cephalosporins in urinary tract infection.

Despite their greater cost compared with other antibiotics, the cephalosporins continue to be used in the treatment of urinary tract infections. Most cephalosporins are excreted primarily by the kidney (by glomerular filtration, tubular secretion, or both) and urinary concentrations routinely exceed 1000 mg/L after even a small dose; exceptions include cefoperazone and ceftriaxone which both exhibit significant biliary excretion, and in patients with significant renal dysfunction only minimal concentrations of these drugs may be present in the urine. Although single-dose treatment of uncomplicated lower urinary tract infections with oral cephalosporins has not been as effective as with other antibiotics, cephalexin, cephradine and cefaclor continue to be used. Early clinical trials with cefuroxime axetil also appear promising for short term and single-dose therapy. The parenteral cephalosporins are reserved for use against more resistant strains or in hospitalised patients with upper urinary tract infections, their choice being directed by in vitro susceptibility tests. Newer agents such as ceftazidime and cefsulodin have been shown to be effective in infections due to P. aeruginosa. Recommended cephalosporin dosage regimens for the common urinary tract pathogens are given.

Malignant group B streptococcal endocarditis associated with saline-induced abortion.

A 20-year-old woman developed acute group B streptococcal endocarditis following saline-induced abortion. In the pre-antibiotic era, most cases of group B streptococcal endocarditis occurred in parturient or postabortal women. Currently, this disease is rarely described in obstetrical patients, and no previous cases following saline-induced abortion have been reported. Purulent pericarditis and a perivalvular abscess were present in our patient and represent only the second instance in which these findings have been documented in this disease.

PIP: This case report describes a 20-year-old woman who developed acute group B streptococcal endocarditis after a saline-induced abortion. She was admitted 2 weeks after an uncomplicated saline-induced abortion for a 16-week pregnancy with a 1-week history of fever, headaches, dizziness, and shortness of breath. The patient showed poor response to antibiotic therapies (initially to nafcillin and gentamicin and then to aqueous penicillin G). 6 to 6 blood cultures after hospital admission showed group B streptococcus which was penicillin sensitive by tetracycline resistant. On Day 3 of admission, a pericardial friction rub was noted and repeat chest x-rays showed marked enlargement of the cardiac shadow. Surgery was performed, and the mitral valve posterior leaflet was necrotic, and a mitral valve prosthesis was placed and an aortic embolectomy was performed. Postoperatively, she was treated with an additional 6-week course of intravenous penicillin, and subsequently, she has remained asymptomatic after 6 months. An addendum to this report, which was only the 2nd such report of endocarditis after saline abortion, describes another case of group B streptococcal endocarditis in a drug abuser after a saline-induced abortion. She required tricuspid valvulectomy and is slowly improving postoperatively.

Recurrent infective endocarditis in a drug addict. Multiple separate episodes in nine years.

Multiple episodes of documented recurrent infective endocarditis occurred in an habitual drug abuser. The six recurrences represent the largest known number reported in a single patient. The case illustrates many characteristics of infective endocarditis and serves to emphasize that recurrent infections are likely if endocarditis risk factors are not eliminated.

Prevalence of nasal colonization with methicillin-resistant Staphylococcus aureus in selected patient populations.

Methicillin-resistant Staphylococcus aureus nasal colonization was investigated in patients arriving for elective cardiovascular surgery, renal patients admitted for arteriovenous graft surgery, and patients transferred to our hospital from other institutions. Renal patients were significantly more likely to be colonized and represent a potential source of MRSA to our institution.