Steel needles used for intravenous therapy. Morbidity in patients with hematologic malignancy.

We studied the morbidity associated with steel needles used for intravenous therapy in adults with hematologic malignancy. Of 148 needles, 52 (36.1%) produced local inflammation, increasing with placements exceeding 24 hours, use of dextrose-containing infusate or intravenous antibiotics, granulocytopenia, and local infection. Eight needles (5.4%) caused local infection and three (2.1%) caused septicemia. Of nine bacteremias occurring in the 43 study patients, none of the five caused by Gram-negative bacilli, but three of the four caused by staphylococci, originated from steel needles. Five of eight local infections and all septicemias occurred with placements exceeding 72 hours (P = .016); each patient with septicemia was granulocytopenic. Intravenous steel needles are a major source of morbidity in patients with granulocytopenia or who are otherwise immunologically compromised. The insertion site should be routinely rotated at least every three days. Nosocomial staphlococcal bacteremia in granulocytopenic patients is likely to be due to an intravenous needle or similar device used for vascular access.

Mucormycosis. A complication of critical care.

Lethal nosocomial mucormycosis developed in three previously well individuals while they were receiving intensive care for acute hemorrhagic pancreatitis, for cardiogenic shock, and for a ruptured intra-abdominal aortic aneurysm. In two cases, the condition was first seen as progressive cavitary pneumonia refractory to antibacterial therapy; Mucoraceae was identified in all three patients only at autopsy. Each patient had received large doses of corticosteroids and broad-spectrum antibiotics, and all had suffered from respiratory failure, acute renal failure with acidosis, and severe hyperglycemia in association with total parenteral nutrition. Mucoraceae should be regarded as an additional nosocomial pathogen in the setting of advanced life-support care.

The relationship between pyuria and infection in patients with indwelling urinary catheters: a prospective study of 761 patients.

BACKGROUND: Pyuria is universally considered as essential for identifying urinary tract infections in noncatheterized patients. The utility of pyuria in the catheterized patient, to identify catheter-associated urinary tract infection (CAUTI), has not been adequately defined. METHODS: We prospectively studied 761 newly catheterized patients in a university hospital; 82 (10.8%) developed nosocomial CAUTI (> 10(3) colony-forming units per milliliter). While catheterized, each patient was seen daily, a quantitative urine culture was obtained, and the urine white blood cell concentration was measured quantitatively using a hemocytometer. RESULTS: The mean urine leukocyte count in patients with CAUTI was significantly higher than in patients without infections (71 vs 4 per microliter; P= .006). Pyuria was most strongly associated with CAUTI caused by gram-negative bacilli (white blood cell count, 121 vs 4 per microliter; P = .03); infection with coagulase-negative staphylococci and enterococci (white blood cell count, 39 vs 4 per microliter; P = .25) or yeasts (white blood cell count, 25 vs 4 per microliter; P = .15) produced much less pyuria. Pyuria with a white blood cell count greater than 10 per microliter (>5 per high-power field in a conventional urinalysis) had a specificity of 90% for predicting CAUTI with greater than 10(5) colony-forming units per milliliter but a sensitivity of only 37%. CONCLUSIONS: In patients with short-term indwelling urinary catheters, pyuria is less strongly correlated with CAUTI than in noncatheterized patients with urinary tract infection. The strongest association is with CAUTI caused by gram-negative bacilli; the association is far weaker for infections caused by gram-positive cocci or yeasts. Most patients with CAUTI are asymptomatic and do not have associated fever. Pyuria should not be used as the sole criterion to obtain a urine culture in a patient with a catheter.

Catheter-associated urinary tract infection is rarely symptomatic: a prospective study of 1,497 catheterized patients.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is the most common nosocomial infection, accounting for more than 1 million cases each year in US hospitals and nursing homes. OBJECTIVE: To define the clinical features of CAUTI. SETTING AND PATIENTS: A university hospital; 1,497 newly catheterized patients. DESIGN: Every day that the catheter was in place, a quantitative urine culture and urine leukocyte count were obtained, and the patient was queried by a research worker regarding symptoms. To more precisely define the role of CAUTI in patients' symptoms, a subset of 1,034 patients, 89 of whom developed CAUTI with more than 10(3) colony-forming units per milliliter, who did not have another potentially confounding site of infection besides the urinary tract, was analyzed. OUTCOME MEASURES: Presence of fever, symptoms commonly associated with community-acquired urinary tract infection, and peripheral leukocytosis. RESULTS: There were 235 new cases of nosocomial CAUTI during the study period. More than 90% of the infected patients were asymptomatic; only 123 infections (52%) were detected by patients' physicians using the hospital laboratory. In the subset analysis, there were no significant differences between patients with and without CAUTI in signs or symptoms commonly associated with urinary tract infection-fever, dysuria, urgency, or flank pain-or in leukocytosis. Only 1 of the 235 episodes of CAUTI that were prospectively studied was unequivocally associated with secondary bloodstream infection. CONCLUSIONS: Whereas CAUTIs are a major reservoir of antibiotic-resistant organisms in the hospital, they are rarely symptomatic and infrequently cause bloodstream infection. Symptoms referable to the urinary tract, fever, or peripheral leukocytosis have little predictive value for the diagnosis of CAUTI.

Enterococcal bacteremia: clinical features, the risk of endocarditis, and management.

The enterococci, members of the group D streptococci and the predominant aerobic streptococci of the gastrointestinal and female genital tracts, have long been recognized as significant pathogens in infective endocarditis. Over the past 2 decades, enterococci have become increasingly important nosocomial pathogens, related to their intrinsic resistance to many antibiotics, especially the cephalosporins, and the greatly increased use of antimicrobial therapy in hospitals. Recent reports have documented an alarming increase in the frequency of high-level resistance to aminoglyclosides, and strains resistant to ampicillin by production of a beta-lactamase and to vancomycin have now been encountered. We have reviewed the clinical features and course of 153 cases of enterococcal bacteremia occurring in a university hospital over the 14-year period, 1970 to 1983, 1) to understand better the importance of enterococci as human pathogens, 2) to identify the clinical features of enterococcal bacteremia, 3) to isolate those findings that help to identify associated endocarditis, and 4) to develop guidelines for more effective antimicrobial therapy of bacteremic enterococcal infections. The annual incidence of enterococcal bacteremia in our center rose three-fold over the period reviewed. In 65 cases (42%), bacteremia was polymicrobial, caused by Enterococcus and at least 1 other microorganism, usually an aerobic gram-negative bacillus. Most bacteremias were nosocomial and derived from infections of the urinary tract (29 cases), intravenous catheters (24 cases), intra-abdominal infections or surgical wounds (46 cases), burn wounds (25 cases), or cholangitis (21 cases); only 1 case originated from a pneumonia. Endocarditis was identified in association with 12 of 35 community-acquired bacteremias, but only 1 of 118 bacteremias acquired in the hospital (P less than .001). Endocarditis was also significantly associated with pre-existent valvular heart disease and cryptogenic bacteremia, and was negatively associated with polymicrobial enterococcal bacteremia (no endocarditis in 65 cases, P less than .001). Isolated enterococcal bacteremia produced an indolent infection rarely associated with shock (3 of 64 cases evaluated, all cases due to valve destruction by endocarditis); conversely, with polymicrobial enterococcal bacteremia, primarily with gram-negative bacilli, shock or disseminated intravascular coagulation developed in 50% of cases (P less than .001).(ABSTRACT TRUNCATED AT 400 WORDS)

Nosocomial bacteremia. An epidemiologic overview.

Each year nosocomial bacteremia develops in approximately 194,000 patients in U.S. hospitals (5/1,000); 75,000 die. These infections portend $.28 to $.86 billion added costs to health care. Most nosocomial bacteremias occur endemically and are secondary bacteremias, caused by postoperative wound or intra-abdominal infections, urinary tract infections or pneumonia; primary bacteremias most frequently originate from intravascular devices, but the source is unrecognized. Between 1965 and 1978, 97 epidemics of nosocomial bacteremia, including 11 of "pseudobacteremia," were reported. In contrast to endemic bacteremias, 78 percent of the epidemics involved primary bacteremias: 33 outbreaks stemmed from infusion therapy in some form, including seven epidemics traced to a contaminated commercial product. Two thirds of endemic nosocomial bacteremias and 79 percent of epidemics are caused by aerobic gram-negative bacilli. Pseudomonas cepacia, Pseudomonas maltophilia, Flavobacterium and Enterobacter agglomerans rarely cause endemic bacteremia and when encountered often signal an epidemic. Whereas predisposing host conditions greatly increase the risk of bacteremia endemically nosocomial epidemics occur mainly in immunocompetent patients and are related to what therapeutic measures have been taken: segregation in a special care unit (58 percent of outbreaks) or exposure to infusion therapy or other invasive procedures involving the bloodstream (65 percent). At present only about one fourth of endemic nosocomial bacteremias are in theory preventable by more consistent application of existent knowledge of asepsis. The potential for prevention seems greatest for epidemic bacteremias, most of which are related to exposure to invasive devices, to a common source of contamination, or both.

Infections caused by aterial catheters used for hemodynamic monitoring.

Utilizing a semiquantitative technique for culturing vascular catheters, we prospectively studied the risk and profile of infection caused by arterial catheters used for hemodynamic monitoring in 95 patients with a high risk of nosocomial infection. Of 130 catheters, 23 (18 per cent) produced local infection (larger than or equal to 15 colonies on semi-quantitative culture) and five septicemia (4 per cent). Sixteen of the 23 local infections and all septicemias occurred with catheter placements exceeding four days (p less than 0.001). Other factors associated with an increased risk of infection included insertion by surgical cut-down rather than percutaneously (ninefold increased rate of bacteremia, p = 0.008) and the presence of local inflammation (12-fold increase, p = 0.009). Systemic antimicrobial therapy (given to 80 per cent of the entire group and to four of the five with septicemia) did not protect against catheter-related infection but may account for the predominance of enterococci, Candida and gram-negative bacilli in these infections. Twelve per cent of all nosocomial bacteremias occurring in this critical care unit population originated from an arterial catheter. Indwelling arterial catheters pose a significant risk of bacteremic infection to ctirically ill patients. The percutaneous mode of placement is preferred; when prolonged arterial cannulation is required, the site should be rotated every four days. Local pain or inflammation, or clinical signs of sepsis without an obvious source should prompt removal and culture of the catheter.

A comparative study of polyantibiotic and iodophor ointments in prevention of vascular catheter-related infection.

Using a semiquantitative technique for culturing material from vascular catheters, we studied by random allocation the efficacy of three regimens for site care of 827 catheters used in adult patients: an iodophor ointment (PI2), ointment containing polymyxin, neomycin and bacitracin (PNB), and use of no topical agent whatsoever (control). Even though this is the largest study of this subject, there was not a sufficient number of catheter-related septicemias to permit valid comparisons (two in each group, 0.7 percent). However, the rate of local catheter-related infection (greater than or equal to 15 CFU on semiquantitative culture), the prelude to related septicemia, was significantly lower in the PNB group (2.2 percent, P = 0.02) as compared with controls (6.5 percent). Use of PI2-treated catheters resulted in one-half fewer infections (3.6 percent) than use of control catheters (P = NS). Staphylococcal infections occurred with 15 control catheters, eight treated with PI2 and two with PNB (P = 0.002). Infections by gram-negative bacilli occurred less frequently in both treatment groups than in controls, but three of four Candida infections, including one septicemia, occurred in the PNB group. Topical antimicrobial agents confer modest benefit in protection against catheter-related infection, primarily for peripheral venous catheters that must remain in place for more than four days. If an ointment is to be used, topical PNB may be preferable for peripheral venous catheters and PI2 ointment for central venous catheters used for parenteral nutrition and for arterial catheters.

Endemic rate of fluid contamination and related septicemia in arterial pressure monitoring.

Contamination of the fluid within intra-arterial infusions used for hemodynamic monitoring has produced epidemic bacteremias, but little data exist on endemic rates of contamination and related septicemia. We prospectively studied 102 intra-arterial infusions used in 56 high-risk patients who required prolonged monitoring. During the study, administration sets were changed every 48 hours, but transducer chamber-domes and continuous flow devices were used until the intra-arterial infusion was discontinued. Cultures were obtained from the transducer-transducer chamber-dome interface and of fluid in the transducer chamber-dome of the 102 intra-arterial infusions; 12 (11.8 percent) showed contamination of transducer chamber-dome fluid, in 8 cases (7.8 percent) associated with concordant bacteremia. In each bacteremia, transducer chamber-dome fluid contained 1 to greater than 10(5) (median, 10(4)) cfu/ml. Four bacteremias are considered definitely related and four, possibly related, to the intra-arterial infusion. In all 12 contaminated intra-arterial infusions and with all eight bacteremias, the transducer chamber-dome had been used for more than two days (P = 0.006). No concordant contamination of transducer-transducer chamber-dome interfaces was identified. (1) Intra-arterial infusions for pressure monitoring cause sporadic septicemias endemically. (2) With prolonged monitoring, transducer chamber-domes and continuous flow devices should be replaced at periodic intervals, ideally with the administration set, every 48 hours; since implementing this policy, only three contaminated intra-arterial infusions and no related septicemias have been detected in 53 intra-arterial infusions monitored over our months (P = 0.02).

Epidemiology of needle-stick injuries in hospital personnel.

Accidental needle sticks sustained by hospital personnel account for many hospital-related injuries, but little information is available dealing with risk factors amenable to control. We reviewed 316 reported needle stick injuries--accounting for one third of all work-related accidents--occurring in employees of our hospital over a 47-month period from 1975 to 1979. Housekeeping (127.0 cases per thousand employees annually) and laboratory personnel (104.7 per thousand) experienced the highest incidence of needle-stick injuries, followed by registered nurses (92.6 per thousand), but 60 percent of all injuries occurred in nursing personnel. Physicians rarely reported needle-stick injuries. Most injuries occurred during disposal of used needles (23.7 percent of all injuries), during the administration of parenteral injections or infusion therapy (21.2 percent), drawing blood (16.5 percent), recapping needles after use (12.0 percent), or handling linens or trash containing uncapped needles (16.1 percent). Sixty percent of the personnel who reported a needle puncture injury sought emergency room treatment where management was variable. The total cost of needle puncture injuries in our hospital over a 27-month period of $6,331. We recommend not recapping used needles and making widely available and promoting use of an efficient needle disposal system. All hospital personnel, including physicians, are urged to report needle-stick injuries to the hospital's Employee Health Service where evaluation and management can be effected most consistently by established protocols.

Defatting catheter insertion sites in total parenteral nutrition is of no value as an infection control measure. Controlled clinical trial.

Defatting the skin with acetone or ether is widely used in the regimen for disinfection of insertion sites of central venous catheters in total parenteral nutrition. The fatty acids secreted by normal skin play an important role in regulation of the cutaneous microbial ecosystem, and it can be questioned whether application of a solvent might paradoxically promote colonization by pathogenic microorganisms. The clinical value of defatting catheter insertion sites was prospectively studied in a controlled, randomized trial: 100 subclavian catheters inserted for total parenteral nutrition were given identical site care except that with one half of the catheters, the site was defatted with acetone prior to catheter insertion and as part of the every-other-day site care regimen. Cutaneous colonization was found in only 130 (24.5 percent) of 531 site cultures in both groups, but was strongly predictive of concordant colonization of the catheter (relative risk, 22.1, p less than 0.001) and catheter-related septicemia (all four cases). No significant differences were observed between the two groups in cutaneous colonization of sites (22.7 percent and 27.0 percent), in colonization of catheters on removal (four catheters [8 percent] in each group) or in catheter-related septicemia (two catheters [4 percent] in each group). However, pain or inflammation of the insertion site was twice as frequent in the acetone group (80 percent versus 35 percent, p less than 0.001). Defatting with acetone as part of the regimen for cutaneous disinfection does not improve microbial removal or reduce the incidence of catheter-related infection, but increases cutaneous inflammation and patient discomfort.

Nosocomial infections from contaminated endoscopes: a flawed automated endoscope washer. An investigation using molecular epidemiology.

Approximately 1 year after purchase of one manufacturer's automated endoscope washing machine, we began to detect heavy contamination of upper gastrointestinal (UGI) endoscopes cultured after cleaning and disinfection in the washer. During the first 6 months of 1988, 77% of surveillance cultures (20-mL flush through the biopsy channel) were positive for gram-negative bacilli (median concentration, 10(5) cfu/mL), most frequently Pseudomonas aeruginosa serotype 10. During the first 19 months of use of the washer, nosocomial post-UGI endoscopy colonization or infections with P. aeruginosa increased 36%. Investigations show that endoscope contamination derives from a flaw in the design of the EW-10 washer: the detergent holding tank, inlet water hose, and air vents cannot be reliably disinfected and contain heavy biofilms that recontaminate the machine after it has been disinfected, as specified by the manufacturer, with glutaraldehyde. Only by rinsing machine-cleansed endoscopes with 70% alcohol followed by forced air drying has reliable disinfection been achieved. Since adaptation of terminal alcohol treatment and drying, post-UGI endoscopy colonization or infection by P. aeruginosa has declined threefold (p less than 0.001). Testing in other centers using the manufacturer's EW-10 or EW-20 washer has shown similar contamination. In three centers, including our own, postendoscopy infections by machine-associated type 10 P. aeruginosa have been confirmed by demonstrating concordance between isolates from contaminated machines or endoscopes and from infected patients by immunoblot of whole cell lysates and by pulsed-field electrophoresis of DraI endonuclease-digested genomic DNA. This problem reaffirms the vulnerability to microbial contamination of water-containing apparatus and equipment in patient care and points up the critical importance of engineering design to prevent contamination.

An attachable silver-impregnated cuff for prevention of infection with central venous catheters: a prospective randomized multicenter trial.

PURPOSE: Percutaneously inserted central venous catheters are widely used. Catheter-related bacteremia or fungemia is the most frequent serious complication of these catheters. In an attempt to reduce the frequency of such infections, a subcutaneous cuff constructed of a biodegradable collagen matrix impregnated with bactericidal silver was developed. Our goal was to assess, in a multicenter clinical trial, the effectiveness of this cuff in preventing catheter-related infection. MATERIALS AND METHODS: Central venous catheters needed for fluid or drug therapy, hemodynamic monitoring, or hyperalimentation in patients in three centers were randomly assigned to be inserted with or without the cuff. Patients and catheters in the two groups were comparable in terms of risk factors predisposing to infection, including colonization of skin about the insertion site. RESULTS: The results with 234 catheters inserted into a new site showed that catheters inserted with the cuff were threefold less likely to be colonized on removal (more than 15 colony-forming units) than were control catheters (28.9 percent versus 9.1 percent, p = 0.002) and were nearly fourfold less likely to produce bacteremia (3.7 percent versus 1.0 percent). Adverse effects from the cuff were not seen. The cuff did not confer protection, however against infection with catheters inserted over a guidewire into old sites. Most of the catheter-related infections identified in this study, including four of the six bacteremias, appear to have been caused by microorganisms colonizing skin about the insertion site, affirming the pathogenetic basis for benefit seen with the cuff in this clinical trial; two may have derived from contamination of the catheter hub. CONCLUSION: This novel, silver-impregnated, attachable cuff can substantially reduce the incidence of catheter-related infection with most percutaneously inserted central venous catheters, can extend the time catheters can be left in place safely, and can prove cost-beneficial.

The pathogenesis and epidemiology of catheter-related infection with pulmonary artery Swan-Ganz catheters: a prospective study utilizing molecular subtyping.

To delineate the pathogenesis and epidemiology of catheter-related infection with Swan-Ganz pulmonary artery (PA) catheters, a prospective clinical study of hospitalized adult medical and surgical patients was done. Role of catheter material was assessed by randomizing insertions to heparin-bonded PA catheters made of polyvinylchloride or polyurethane. Sources of infection and pathogenesis were studied by culturing skin, the introducer, the PA catheter tip, all hubs, infusate from each lumen, and the extravascular portion of the PA catheter beneath the external protective plastic sleeve. Concordance between isolates from sources and infected catheters was determined by speciation, antibiogram, and for coagulase-negative staphylococci, plasmid profile analysis. Risk factors for infection were determined by stepwise logistic regression. Overall, 65 (22%) of 297 Swan-Ganz catheters showed local infection of the introducer (58 catheters) or the intravascular portion of the PA catheter (20 catheters); only two catheters (0.7%) caused bacteremia. Eighty percent of infected Swan-Ganz catheters (the introducer or PA catheter) showed concordance with organisms cultured from skin of the insertion site, 17% with a contaminated hub and 18% with organisms contaminating the extravascular portion of the PA catheter beneath the sleeve. Isolates from infected PA catheters were most likely to show concordance with concomitantly infected introducers (71%). Cutaneous colonization of the insertion site with greater than 10(2) cfu/10 cm2 (relative risk [RR] 5.5; p less than 0.001), insertion into an internal jugular vein (RR 4.3; p less than 0.01), catheterization greater than 3 days (RR 3.1; p less than 0.01), and insertion in the operating room using less stringent barrier precautions (RR 2.1; p = 0.03) were each associated with a significantly increased risk of catheter-related infection. The risk of bacteremic infection with Swan-Ganz catheters is now low, in the range of 1%, with reasonable care. Swan-Ganz catheters are vulnerable to contamination from multiple sources, but the patient's skin is the single most important source of organisms causing invasive infection, which in most cases involves the introducer rather than the PA catheter. Heavy colonization of the insertion site, percutaneous insertion in the internal jugular vein rather than subclavian vein, catheterization longer than 3 days, and insertion with less stringent barrier precautions significantly increase the risk of catheter-related infection. These findings hold promise for application to management of Swan-Ganz catheters and research in catheter design to reduce the risk of catheter-related infection.

Epidemiology of hospital sharps injuries: a 14-year prospective study in the pre-AIDS and AIDS eras.

The world pandemic of acquired immunodeficiency syndrome (AIDS) has focused enormous attention on the problem of accidental sharps injuries sustained by health care workers (HCWs) and the risk of occupationally acquired infection by human immunodeficiency virus (HIV). At the 1980 Conference, we reported a 4-year epidemiologic study (1975-1979) of sharps injuries in HCWs at our hospital. Using the same reporting system and analyses, we now report the epidemiology of sharps injuries in our center during the current AIDS era (1987-1988) and assess trends over the 14-year period. Despite greatly increased institutional efforts to prevent sharps injuries, the annual incidence has increased more than threefold (60.4 to 187.0/1,000 HCWs), reflecting better reporting and increased exposure. Reported injuries by house officers have increased ninefold. Adjusting for inflation, the direct costs of sharps injuries has increased sevenfold ($5,354 to $37,271/year). Environmental service HCWs (305.8 sharps injuries per 1,000 employees) now have the highest incidence in our center, followed by nursing personnel (196.5/1,000) and laboratory personnel (169.9/1,000), but as in 1975-1979, two thirds of all injuries occur in nursing personnel. Although phlebotomy team members have a very low risk per procedure (1/26,871 draws), their annual incidence is extraordinarily high, 407.0/1,000. Injuries continue to occur mainly during disposal of waste, linen, or used procedure trays (19.7% of all injuries), administration of parenteral injections or infusion therapy (15.7%), surgery (16.0%), blood drawing (13.3%), or recapping of used needles (10.1%). Making disposal units available at every bedside has reduced injuries from needle disposal two-fold since 1975-1979. With consistent application of a stringent postexposure protocol, and wide acceptance of the hepatitis B vaccine, we have had no sharps injury-related infections during the past 3 years. These data indicate the increasing risk, complexity and cost of sharps injuries in HCWs and the need for more innovative--ideally, technology-based--approaches to prevention. Certain groups of HCWs are at very high risk. Comprehensive postexposure protocols that are uniformly applied can provide substantial protection to exposed HCWs.

Nationwide epidemic of septicemia caused by contaminated intravenous products. I. Epidemiologic and clinical features.

Between mid-1970 and April 1, 1971, Enterobacter cloacae or E. agglomerans septicemia developed in 378 patients in 25 American hospitals while they were receiving intravenous products manufactured by one company. Each of the hospitals noted a marked increase in the incidence of such septicemia during this period. Enterobacter agglomerans (formerly designated Erwinia, herbicola-lathyri group) was better known as a plant pathogen and had been a human blood pathogen only rarely in the past. Septicemia caused by E. cloacae had also been uncommon.

A prospective, randomized, double-blind study of trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation: clinical efficacy, absorption of trimethoprim-sulfamethoxazole, effects on the microflora, and the cost-benefit of prophylaxis.

PURPOSE: To determine the efficacy of long-term prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) for prevention of bacterial infection following renal transplantation, the absorption of TMP-SMZ in transplant patients, the effects of prophylaxis on the microflora, and the cost-benefit of prophylaxis. PATIENTS AND METHODS: One hundred thirty-two adult patients selected to undergo renal transplantation participated in a randomized, double-blind, placebo-controlled trial. RESULTS: Patients randomized to receive TMP-SMZ experienced fewer hospital days with fever (3.3% versus 7.7%, p less than 0.001) and significantly fewer bacterial infections during the transplant hospitalization after removal of a urethral catheter (0.76 versus 1.88 per 100 days, p less than 0.005) and following discharge from the hospital (0.08 versus 0.30 per 100 days, p less than 0.001). During the transplant hospitalization, a daily dose of 320/1,600 mg was highly effective for prophylaxis whereas 160/800 mg daily gave unexpectedly low blood levels and was effective only for prevention of urinary tract infections after catheter removal. Prophylaxis was most effective in prevention of infections of the urinary tract (24 versus 54, p less than 0.005) and bloodstream (one versus nine, p less than 0.01) and infections caused by enteric gram-negative bacilli (four versus 46, p less than 0.001), enterococci (six versus 22, p = 0.006), or Staphylococcus aureus (one versus nine, p = 0.01). Prophylaxis did not prevent urinary tract infection associated with urethral catheters in the early posttransplant period, but after catheter removal, reduced the risk of urinary tract infection threefold (p less than 0.001). No significant differences in colonization by TMP-SMZ-resistant gram-negative bacilli were identified between the two groups; patients given TMP-SMZ were, paradoxically, less likely to become colonized by candida, probably because of less exposure to antibiotics for treatment of infection. Recipients of prophylaxis did not have a higher rate of infection caused by TMP-SMZ-resistant bacteria or Candida; however, their infections were more likely to be caused by resistant bacteria than infections in patients in the placebo group (62% versus 18%, p less than 0.001). CONCLUSIONS: Prophylaxis with TMP-SMZ, which is well tolerated, significantly reduces the incidence of bacterial infection following renal transplantation, especially infection of the urinary tract and bloodstream, can provide protection against Pneumocystis carinii pneumonia, and is cost-beneficial. Subnormal absorption of TMP-SMZ in the early posttransplant period mandates 320/1,600 mg daily for optimal benefit. Prophylaxis has little discernible effect on the microflora.

OKT3 salvage therapy in a quadruple immunosuppressive protocol in cadaveric renal transplantation.

Since the introduction of OKT3 at our center in January 1986, we have performed 246 cadaveric renal transplants (220 primary, 26 nonprimary). All patients received quadruple immunosuppression consisting of prednisone, azathioprine, and the sequential use of Minnesota antilymphoblast globulin (MALG) and cyclosporine. OKT3 (Orthoclone OKT3) therapy was reserved for corticosteroid- and/or ALG-resistant rejection. Of the 246 patients, 138 developed one or more rejection episodes (56.1%). Ninety-seven (70.3%) were successfully reversed with prednisone and/or ALG, whereas 41 (29.7%) required additional treatment with OKT3. Initial graft salvage occurred in 34 (82.9%) patients treated with OKT3, but rejection recurred in 18 (52.9%) and was successfully reversed in only 6 patients. However, the rate of recurrent rejection was much lower in patients given OKT3 early (14%), shortly after it was apparent that high-dose corticosteroid therapy was proving ineffective, than in patients who received OKT3 after a prolonged or second course of corticosteroids (64%) or ALG (60%). Graft survival after a mean follow-up interval of 11 months in all OKT3-treated patients was 54%. One or more infections occurred in 19 (46%) patients treated with OKT3. Patients developing infections following OKT3 therapy received significantly larger total doses of prednisone during graft rejection (46.3 mg/kg vs. 27.9 mg/kg, P less than .05) than OKT3-treated patients who did not develop infectious complications. Our experience shows that use of OKT3 for treatment of corticosteroid- and/or ALG-resistant rejection is associated with a high rate of recurrent rejection, except when given early, as soon as it is clear that high-dose corticosteroid therapy is not reversing the rejection episode. It further suggests that prolonged administration of high-dose corticosteroids and possibly ALG for the treatment of rejection prior to beginning OKT3 greatly increases the rate of infection following OKT3 therapy.

Increased infections associated with the use of OKT3 for treatment of steroid-resistant rejection in renal transplantation.

We compared the infections encountered in 23 renal transplant patients given the monoclonal anti-T-cell antibody, Orthoclone OKT3 (OKT3), for treatment of steroid-resistant rejection in 1986 and in 23 control patients from 1984 to 1985 with resistant rejection matched demographically, for severity of rejection and for risk factors predisposing to infection, who did not receive OKT3; recipients of OKT3 received substantially less prednisone, cyclosporine, and antilymphocyte globulin (ALG) than control patients for treatment of the rejection episode. Fourteen (61%) patients given OKT3 developed one or more infections in the 3-month period following treatment as compared with 9 control patients (39%) given conventional antirejection therapy with high-dose steroids and, usually, ALG. Patients given OKT3 were significantly more likely to develop serious infections (pneumonia, bacteremia, meningitis, or severe viral infection; 16 episodes vs. 4, P = .02). Six recipients of OKT3 (26%) acquired infections typically encountered in states associated with depressed cell-mediated immunity (CMI)--Listeria sepsis (2), disseminated nocardiosis and Mycobacterium tuberculosis infection (1), cytomegalovirus (CMV) pneumonia (1), Yersinia infection with severe dermatophytosis (1), and Epstein-Barr virus-associated lymphoproliferative syndrome (1)--as compared with 1 case of mild CMV infection in the control group (P = .08). Trimethoprim-sulfamethoxazole (TMP-SMZ) was given to 19 patients in each group; all 4 recipients of OKT3 who did not receive TMP-SMZ prophylaxis developed life-threatening infection, 3, bacteremia (2 with Listeria) and 1, disseminated nocardiosis and M tuberculosis infection. These data suggest that OKT3 given for treatment of resistant rejection in renal transplantation predisposes the patient to serious infection, particularly with opportunistic pathogens characteristically associated with depressed cell-mediated immunity. Prophylaxis with TMP-SMZ, which is safe, well tolerated, and effective for reducing the incidence of infection in renal transplantation, may be especially important during OKT3 therapy.

Absence of infection with human immunodeficiency virus in Peruvian prostitutes.

We serologically tested 140 female prostitutes (mean age, 30 years) from the port city of Callao, Peru, for evidence of infection with human immunodeficiency virus (HIV), Chlamydia trachomatis, Treponema pallidum, herpes simplex viruses (HSV) I and II, and hepatitis B virus. The women had worked as prostitutes for an average of 5 years; one-fourth serviced foreign visitors exclusively, mainly sailors. Only 4 women used condoms, and only 1 woman gave a history of parenteral narcotic abuse, although 53% were regularly exposed to unsterile needles outside the medical setting for injections of vitamins, antibiotics, or steroids; another 29% are thought to probably use unsterile needles. None of the 140 prostitutes screened was seropositive for HIV, despite a very high prevalence of antibody to T. pallidum (24%), C. trachomatis (97%), HSV I and II (100%), and hepatitis B (51%); 5% were HbsAg positive. These data indicate that HIV has not yet been introduced into female prostitutes in the Peruvian port city. We believe that widespread use of unsterile needles in developing countries, such as Peru, represents a serious health threat and will amplify the spread of HIV, once introduced.