Clinical impact of rapid identification and susceptibility testing of bacterial blood culture isolates.

Two hundred twenty-six patients with bacteremia were prospectively enrolled in a randomized trial that was performed to determine the clinical impact of the receipt of in vitro microbiological data by the physician soon after organism detection as opposed to having the physicians wait until similar data were available by routine methods. Identification and antibiotic susceptibility patterns of 110 isolates were determined by direct inoculation of the Vitek AutoMicrobic system (Vitek Systems, Inc., Hazelwood, Mo.) with a sample from a positive blood culture vial. One hundred sixteen isolates were processed by routine methods. Microbiological results were available within an average of 8.8 h by the direct method versus an average of 48 h by the routine method. In both groups an infectious disease fellow used the information to make therapeutic recommendations to the responsible physician. When compared with that provided by the routine method, the information provided by the direct method was significantly more likely to result in an initiation of antibiotic therapy, a change to more effective therapy, or a change to less expensive therapy. Recommendations were significantly more likely to be followed in patients whose isolates were processed by the direct method versus the routine method. A projected savings of $158 per patient was estimated for the patients who were changed to less expensive therapy or in whom antibiotics were discontinued because results were available sooner. These cost savings, coupled with changes in therapy made for reasons of efficacy, support the usefulness of the earlier reporting of the identity and antibiotic susceptibility patterns of bacterial blood culture isolates.

Considerations in the therapy of septic shock.

In summary, gram-negative sepsis is unique among infectious illnesses in that it is a disorder that recruits endogenous physiologic processes to mediate tissue injury. This host damage frequently occurs in the absence of microbial invasion of affected organs. The resultant hypotension, coagulation defects, and organ dysfunction may be associated with serious morbidity or may contribute to mortality. Ultimately, however, mortality in patients with septic shock depends on the nature of the infectious process and the severity of the underlying illnesses. Unfortunately, attempts to aggressively treat septic patients with a formidable array of antimicrobial and pharmaceutical agents have not remarkably reduced mortality. Nor does it seem likely that future elucidation of the inflammatory mechanisms of sepsis will lead to the generation of therapeutic agents that will significantly improve survival. On the other hand, prophylactic or therapeutic modalities that deter colonization or invasion by pathogenetic organisms or that alter the ability of pathogens to evoke adverse host responses may be more likely to impact on the incidence and morbidity of gram-negative bacillary infections. Until modifications in the initial interactions of gram-negative pathogens with human hosts can be realized, the mortality of gram-negative sepsis is likely to remain high.

Future trends in aminoglycoside therapy.

The aminoglycosidic aminocyclitols have been utilized extensively for three decades. Nonetheless, the future use of this class of agents has been questioned of late. Recognized inadequacies of the aminoglycosides and the development of new antibiotics with significant activity against gram-negative bacilli are commonly cited reasons for the theorized decline of these compounds. However, resistance to newly developed antibiotics already has become evident. This insures a continuing role for the aminoglycosides in the treatment of nosocomial infections. Aminoglycosides will have continued use as empiric, potentially synergistic therapies for hospital-acquired infections in neutropenic patients with bacteremia, in enterococcal endovascular infections, and in patients with serious infections associated with Pseudomonas aeruginosa. Those factors that will influence the future role of aminoglycosides in these settings will include economic, administrative, and space pressures to restrict the number of antibiotics available in hospitals, the discovery of novel antibiotics, the utility of combination therapies employing an aminoglycoside and newly available drugs, the comparative toxicities of new antimicrobial regimens, and considerations of cost containment.

Use of ceftazidime in the treatment of nosocomial lower respiratory infections.

Patients with hospital-acquired lower respiratory infections pose both diagnostic and therapeutic challenges. Such infections are commonly seen in critically ill patients. When nosocomial pneumonia is suspected, treatment is generally initiated with broad-spectrum antibiotics before culture results become available. The usual therapeutic regimen includes an aminoglycoside with or without a beta-lactam agent. In a clinical efficacy study of a single agent, ceftazidime, in the treatment of 20 adults with hospital-acquired lower respiratory infection, 18 patients showed clinical improvement with ceftazidime therapy and pathogens were eradicated in 11. Therapeutic failures occurred in two patients who received empiric therapy prior to the isolation of pathogens resistant to ceftazidime. The median minimal inhibitory concentration of ceftazidime for the isolated pathogens was 0.78 micrograms/ml. Of the 15 patients infected with Pseudomonas aeruginosa, 14 showed a favorable clinical response. Therapy-limiting side effects occurred in two patients and bacillary resistance developed in one patient. The efficacy and safety of ceftazidime in the treatment of hospital-acquired pneumonias were comparable to results previously demonstrated for amikacin, cefotaxime, and imipenem in studies conducted at our institution. In studies reported in the literature, 44 of 51 patients (86 percent) with nosocomial pneumonia who were treated with ceftazidime had a favorable clinical response to therapy. The patients included in these studies were neither neutropenic nor commonly bacteremic, and none had cystic fibrosis. Ceftazidime appears to be a useful agent in the treatment of selected patients with nosocomial pneumonias, including those due to P. aeruginosa.

A review of the use of cefotaxime in the treatment of skin and skin structure infections, with special reference to gram-positive pathogens.

Data compiled from computer-generated summaries of patient records submitted to Hoechst-Roussel Pharmaceuticals were reviewed regarding the efficacy and toxicity of cefotaxime in the therapy of skin and skin structure infections associated with gram-positive pathogens. In addition, published open and comparative trials employing cefotaxime in gram-positive and gram-negative skin infections were evaluated with respect to the pathogens isolated and the nature, severity and bacteriological and clinical outcome of the treated infections. Within the limitations of the data reviewed, cefotaxime appeared to be a safe and effective therapy in greater than 90% of infections including cellulitis, abscesses and necrotizing ulcers of the skin and subcutaneous tissues when associated with the isolation of susceptible gram-negative bacilli, methicillin-susceptible Staphylococcus aureus, or aerobic or anaerobic gram-positive pathogens susceptible to aqueous penicillin G. The data would indicate that cefotaxime is a suitable therapy for patients with presumed polymicrobial, non-crepitant infections of the skin or skin structures pending microbiological studies. However, cefotaxime cannot be recommended for similar infections due to organisms such as methicillin-resistant S. aureus or Pseudomonas aeruginosa that are commonly resistant to cefotaxime in vitro. Data regarding skin and skin structure infections associated with Clostridium spp. and enterococcal group D streptococci are either lacking or inconclusive with respect to the utility of cefotaxime.

Cefsulodin therapy for osteomyelitis due to Pseudomonas aeruginosa.

The results of treating chronic Pseudomonas aeruginosa osteomyelitis with cefsulodin at Rush-Presbyterian-St. Luke's Medical Center (RPSLMC) and eight other institutions are summarized. Eleven patients whose infections were proven by bone-biopsy culture were treated with cefsulodin at RPSLMC; one received two courses of treatment. Efficacy of therapy was evaluated for eight patients, all of whom had a polymicrobial infection. The average age of the patients was 52.3 years (range, 28-85). All had serious underlying illnesses or associated conditions. The mean inhibitory concentration of cefsulodin for the isolates of P. aeruginosa was 3.125 micrograms/ml (range, 0.78-6.25 micrograms/ml). Two patients received concomitant therapy with antibiotics not active against P. aeruginosa. Surgical debridement was performed in six of the eight patients. A favorable response was demonstrated in six of the eight patients. Follow-up for seven patients ranged from one week to 12 months, and in the eighth patient follow-up was 32 months. One patient relapsed twice. Seven possible complications of therapy were observed in five of the 11 patients who received cefsulodin; in three of these patients cefsulodin had to be discontinued. In studies of osteomyelitis conducted at other institutions, 10 of 14 patients for whom therapy could be evaluated had a favorable response to cefsulodin. Cefsulodin is a useful agent for the treatment of chronic osteomyelitis associated with P. aeruginosa.

Ceftazidime in the therapy of serious Gram-negative bacillary infections.

Eighteen patients were evaluated after treatment with ceftazidime: these included nine nosocomial lower respiratory tract infections, four soft tissue infections, three bacteraemias and two bone infections. Thirty-five bacterial pathogens were isolated from these 18 patients. Two were resistant to ceftazidime and required alternative therapy. Sixteen of the 18 evaluable patients had a favourable response to ceftazidime. Seven of eight patients with Pseudomonas aeruginosa lower respiratory tract infections responded favourably. Fifteen possible complications were observed in ten of 23 patients who received ceftazidime. In three patients ceftazidime was discontinued due to possible complications of therapy. This trial provides preliminary support for the use of ceftazidime as an alternative to aminoglycosides in the treatment of serious infections caused by Gram-negative organisms, including Ps. aeruginosa.

Clinical efficacy of cefotaxime in serious infections.

Thirty-five patients underwent 38 treatment courses with cefotaxime. Documented infections included 11 bacteremias, 7 cases of nosocomial pneumonia, 6 surgical wound infections, 3 bone infections, 1 biliary infection, and 1 urinary tract infection. Granulocytopenic patients with fever received 15 courses of empiric cefotaxime therapy alone; in 8 courses, no definite site of infection or pathogen was isolated. Broad-spectrum antibiotics had been administered to 23 patients before cefotaxime. Thirty-seven bacterial pathogens were isolated from 25 patients. Three such pathogens were resistant to cefotaxime and required alternative therapies. Pathogenic isolates included 13 Serratia marcescens, 12 Pseudomonas aeruginosa, 4 Escherichia coli, 2 Klebsiella pneumoniae, 2 Providencia stuartii, 1 Enterobacter cloacae, 1 Haemophilus influenzae, 1 Enterococcus, and 1 Staphylococcus aureus. Of the treatment courses, 25 of 38 resulted in a favorable response to cefotaxime, including 9 of 15 in granulocytopenic patients. Superinfection was seen in one patient. The emergence of resistance was documented in another patient. Of 15 patients with multiply resistant pathogens, 12 improved with cefotaxime. Of 12 patients with Pseudomonas aeruginosa, 6 favorably responded. Possible complications of cefotaxime were observed in 14 of 42 treatment courses. Cefotaxime is most useful in treatment of infections due to multiply resistant, gram-negative pathogens other than Pseudomonas aeruginosa.