Enterococcal superinfection and colonization with aztreonam therapy.

Patients were given aztreonam (SQ 26,776) parenterally for the treatment of various gram-negative infections. During or shortly after therapy, 8 (17.8%) of 45 patients became infected with or colonized by enterococcus. These eight cases included eight urinary tract isolates; one of these cases subsequently developed bacteremia. Five patients required further antimicrobial therapy directed against enterococcus. Patients receiving aztreonam are at risk for the development of enterococcal superinfection or colonization.     

Randomized clinical trial of aztreonam and aminoglycoside antibiotics in the treatment of serious infections caused by gram-negative bacilli.

Aztreonam was compared with aminoglycoside antibiotics (tobramycin and amikacin) in a randomized, prospective, clinical trial in serious infections caused by gram-negative bacilli (GNB). A total of 43 evaluable patients with 47 infected sites were treated with aztreonam, and 41 evaluable patients were treated with aminoglycosides for 43 infections. Of patients treated with aztreonam, 17 were bacteremic, as were 12 of those treated with aminoglycosides. Clinical and microbiologic response rates were similar, except that only 5 of 11 patients with pneumonia were considered to be clinically cured with aminoglycoside therapy, while 5 of 6 patients with pneumonia treated with aztreonam were cured. Renal impairment was observed in 9 of 54 patients who received aminoglycoside antibiotics, but in only 2 of 53 patients treated with aztreonam. Hearing impairment developed in one patient treated with tobramycin. Transient elevations of serum transaminase levels occurred in 9 of 53 patients treated with aztreonam and in only 2 of 54 aminoglycoside-treated patients. Diarrhea and superinfection occurred with equal frequency in both groups. Serum concentrations of bactericidal activity could not be correlated with the outcome of therapy. Aztreonam appears to have comparable clinical efficacy with aminoglycoside antibiotics for the treatment of serious infections caused by aerobic and facultative GNB. Its use as a single agent for the treatment of serious lower respiratory infections caused by GNB warrants further evaluation.     

Efficacy and safety of low dose aztreonam in the treatment of moderate to severe gram-negative bacterial infections

One hundred and fifty-three patients with moderate to severe infections due to Gram-negative bacteria, including septicaemia (60 cases), lower respiratory tract infection (32 cases), intra-abdominal infection (40 cases) and urinary tract infection (21 cases), were treated with aztreonam 1 g every 12 h. This dosage is lower than usual. Criteria for inclusion included documented Gram-negative bacterial infections, and assessment of the severity of the disease by a scoring system for both community and hospital acquired infections. No other antibiotic active against Gram-negative bacteria was allowed. In 71 patients, in whom Gram-positive or anaerobic organisms were detected or suspected, additional agents effective against these organisms were administered. One hundred and forty-one patients (92.2%) were cured with a mean duration of treatment of 10.9 +/- 4.0 days. None of the Gram-negative bacteria initially isolated became resistant to aztreonam. Colonization, generally by a Gram-positive organism, was observed in 27 patients and superinfection in five. Aztreonam was well tolerated. This study suggests that a daily dosage of 2 g of aztreonam should be sufficient in the treatment of moderate to severe Gram-negative bacillary infections due to sensitive organisms.     

Evaluation of lamoxactam in the treatment of severe bacterial infections

We investigated the clinical efficiency and safety of lamoxactam for treatment of 28 episodes of infection in 26 adult patients (15 males and 11 females) whose ages ranged from 17 to 83 years (mean 48.7). 4 patients had 'ultimately fatal diseases' and the remaining 22 had 'nonfatal diseases'. The clinical condition at the beginning of treatment was 'critical' or 'poor' in 15 cases. Episodes of infection treated were: 14 intraabdominal, 9 bacteremia, 5 nephro-urinary, 3 osteomyelitis, and a miscellaneous group including pneumonia, soft tissue, parameningeal focus and infected V-P shunt. A total of 34 microorganisms were responsible for 25 episodes of infection. 15 and 10 episodes were mono- and polymicrobial, respectively. Isolated microorganisms included 13 aerobic facultative gram-negative bacillus, 5 facultative gram-positive cocci, and 16 anaerobes. Total dosage of lamoxactam administered by patient ranged from 24 to 234 g (mean 57.6 g), and mean duration of therapy was 15.2 days (range 8-42 days). The overall rate of clinical response to lamoxactam was excellent, amounting to 84% of episodes and 91% of patients. Local and general tolerance was good, and lamoxactam had to be discontinued only once during therapy due to an episode of neutropenia. Enterococcal colonization (5 of 26 patients, 19%) and superinfections (3 of 26 cases, 11.5%) were undesirably frequent in our patients. Lamoxactam seems to be an effective and safe single-agent therapy for many bacterial infections. The possibility of enterococcal colonization and superinfections should be monitored, specially in patients with urinary or intraabdominal infections.     

Aztreonam: the first monobactam

There are several areas in which the use of aztreonam seems logical. Infections caused by organisms sensitive to aztreonam that are known to be multiresistant to other agents can be treated directly with aztreonam in single, directed therapy, thus making the use of more toxic agents unnecessary. In types of infection in which both gram positive and gram negative bacteria are present, aztreonam can replace the usual aminoglycoside component of the therapeutic regimen. In settings of mixed infections suspected of being caused by drug-resistant strains of Enterobacteriaceae and/or P. aeruginosa, aztreonam can be combined with an agent active against gram positive organisms or with one active against anaerobes. Aztreonam has proven to be effective, safe therapy for serious and life-threatening infections caused by multiresistant aerobic gram negative bacteria. It should be used in combination with drugs that inhibit gram positive species if the etiology of the infection is not known, particularly in the immunocompromised, neutropenic patient. Doses of 1 g every 8 to 12 hours will be adequate for treatment of infections caused by most Enterobacteriaceae. Whether 2 g doses every 8 hours would be preferred for treatment of systemic Pseudomonas infections remains to be determined. Urinary infections caused by gram negative bacteria can be treated with 500 mg administered IM once or twice daily. The dosage of aztreonam should be adjusted in patients with renal failure. Clearly, aztreonam is a useful addition to the antimicrobial agents available to the physician.     

Diagnostic accuracy of G-CSF,IL-8, and IL-1ra in critically ill children with suspected infection

OBJECTIVE: To elucidate the diagnostic accuracy of granulocyte colony-stimulating factor (G-CSF), interleukin-8 (IL-8), and interleukin-1 receptor antagonist (IL-1ra) in identifying patients with sepsis among critically ill pediatric patients with suspected infection. DESIGN AND SETTING: Nested case-control study in a multidisciplinary neonatal and pediatric intensive care unit (PICU) PATIENTS: PICU patients during a 12-month period with suspected infection, and plasma available from the time of clinical suspicion (254 episodes, 190 patients). MEASUREMENTS AND RESULTS: Plasma levels of G-CSF, IL-8, and IL-1ra. Episodes classified on the basis of clinical and bacteriological findings into: culture-confirmed sepsis, probable sepsis, localized infection, viral infection, and no infection. Plasma levels were significantly higher in episodes of culture-confirmed sepsis than in episodes with ruled-out infection. The area under the receiver operating characteristic curve was higher for IL-8 and G-CSF than for IL-1ra. Combining IL-8 and G-CSF improved the diagnostic performance, particularly as to the detection of Gram-negative sepsis. Sensitivity was low (<50%) in detecting Staphylococcus epidermidis bacteremia or localized infections. CONCLUSIONS: In this heterogeneous population of critically ill children with suspected infection, a model combining plasma levels of IL-8 and G-CSF identified patients with sepsis. Negative results do not rule out S. epidermidis bacteremia or locally confined infectious processes. The model requires validation in an independent data-set.     

Aztreonam treatment of Pasteurella multocida cellulitis and bacteremia

OBJECTIVE: To report a case of Pasteurella multocida cellulitis and bacteremia treated successfully with aztreonam. CASE SUMMARY: An 81-year-old white man with multiple antibiotic allergies was admitted with severe cellulitis of the left arm and bacteremia due to P. multocida. The patient was treated for 14 days with aztreonam and had complete resolution of the infection. DISCUSSION: To our knowledge, this is the first published case describing successful treatment of P. multocida cellulitis and bacteremia with aztreonam. Antimicrobials recommended for use in P. multocida infections include penicillin, ampicillin, amoxicillin, second- and third-generation cephalosporins, tetracyclines, fluoroquinolones, and trimethoprim/sulfamethoxazole. There is very little information in the current literature regarding the activity of aztreonam toward P. multocida. CONCLUSIONS: This case demonstrates the potential use of aztreonam for P. multocida cellulitis and bacteremia in those instances where antibiotics of choice cannot be given.     

Piperacillin, beta-lactam inhibitor plus gentamicin as empirical therapy of a sequential regimen in febrile neutropenia of pediatric cancer patients

The beta-lactam/beta-lactamase inhibitor combinations are a good choice for empirical antimicrobial therapy in febrile neutropenic patients, because their antibacterial spectra include both gram-negative and gram-positive pathogens. This trial was initiated to assess the efficacy and safety of piperacillin with the beta-lactam inhibitors sulbactam (PSG group) or tazobactam (PTG group) and gentamicin as initial therapy in febrile neutropenia of pediatric patients. In a prospective study, 239 episodes of fever and neutropenia were analyzed for the clinical and microbiological response dependent on infection etiology and treatment group: 66.5% of episodes were classified as fever of unknown origin (FUO) and 33.5%, as microbiologically or clinically documented infections; 19.2% of all episodes were due to bacteremia, predominantly caused by gram-positive organisms (69.6%). The response to the initial therapy was 55.2% overall and 65.4% in episodes of FUO with a significant higher success rate in the PSG group than in the PTG group (70.1% vs. 52.4%, P=0.039), and 35.0% in documented infections. In episodes with documented infection longer duration of fever and antimicrobial therapy was recorded than for FUO episodes. Four patients died of causes related to infection. Fever relapse occurred in 26 episodes (11.1%), predominantly in patients who were still neutropenic. Toxic side effects were minimal. The initial therapy of piperacillin with sulbactam or tazobactam in combination with gentamicin is well tolerated, and its efficacy is comparable to that of other combination therapies or of monotherapy with beta-lactam antibiotics in pediatric neutropenic cancer patients.     

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.     

Efficacy of a twelve-hourly ceftriaxone regimen in the treatment of serious bacterial infections

Eighteen patients with 21 serious infections were treated with ceftriaxone, 1 g intravenously every 12 h, for a mean duration of 8 days. Eighteen gram-negative and two gram-positive organisms were isolated. Sites of infection included blood (three patients), urinary tract (six patients), respiratory tract (seven patients), biliary tract (three patients), ascitic fluid (one patient), and skin (one patient). Serum, bile, and ascitic fluid concentrations of ceftriaxone were in excess of the minimal bactericidal concentration required for the infecting organism in all cases. A bacteriological response was demonstrated in 94% of the infections. A clinical response occurred in four infections from which no pathogens were recovered. In one patient, ceftriaxone failed to eradicate a peritoneal infection due to Bacteroides fragilis. In two patients, superinfection with enterococci developed both during and after therapy. Systemic tolerance to ceftriaxone was excellent.     

Pharmacokinetics, in-vitro activity, therapeutic efficacy and clinical safety of aztreonam vs. cefotaxime in the treatment of complicated urinary tract infections

The minimal inhibitory concentrations (MICs) of aztreonam and cefotaxime were determined against 400 isolates from urological in-patients with complicated and/or hospital acquired urinary tract infections (UTI). Against the Gram-negative rods the activities of both antibiotics were comparable except for higher activity of aztreonam against Pseudomonas aeruginosa. The pharmacokinetic study in nine elderly patients showed a prolonged plasma half life of aztreonam (2.7 h) as compared to younger volunteers (1.6-1.9 h). In a prospective randomized study 39 urological patients with complicated and/or hospital acquired UTI were treated with 1 g aztreonam or cefotaxime iv twice daily for 4 to 15 days. Cure was obtained in 5 out of 18 patients in the aztreonam and 7 out of 20 patients in the cefotaxime group. There were 3 superinfections, 7 relapses and 3 reinfections in the aztreonam group and 1 failure, 1 superinfection, 6 relapses and 5 reinfections in the cefotaxime group. There was no significant difference in therapeutic efficacy between the two antibiotics. Both antibiotics were tolerated well and seem to be equally effective in the treatment of complicated UTI caused by sensitive organisms.     

The use of aztreonam in serious gram-negative infections

Aztreonam, the first available monobactam, was used to treat 38 episodes of serious infection presumed or proven to be due to aerobic Gram-negative bacteria. On 15 occasions it was used empirically in combination with other antibiotics and on 23 occasions as therapy specifically directed against Gram-negative pathogens. Thirty-six Gram-negative infections were documented (including 23 septicaemias) and 35 of them were clinically cured by aztreonam. Likewise 35 of the 36 aerobic Gram-negative pathogens were eradicated. Both of the failures (one clinical and one microbiological were Salmonella infections). No major toxicity was seen but there were five superinfections (four due to Streptococcus faecalis). The results indicate that aztreonam is a useful alternative to the aminoglycosides or the broad-spectrum beta-lactam antibiotics for the treatment of severe Gram-negative infections.     

Characteristics of community-acquired and health care-associated Staphylococcus aureus bacteremia in patients treated at the emergency department of a teaching hospital

The changing epidemiology of Staphylococcus aureus bacteremia has been noted worldwide. This enhanced awareness appears to be closely associated with the evolution of health care systems. To further delineate this change and to clarify the prevalence of true community-acquired methicillin-resistant S. aureus (MRSA), reclassification for community-onset bacteremia was proposed. Exposure to health care system, such as nursing home residence, regular outpatient invasive interventions, and prior hospitalization within 1 year, was identified among the community-onset S. aureus bacteremia patients. During the 1-year study period, 102 episodes of S. aureus bacteremia from the emergency department patients of a teaching hospital were prospectively enrolled. Nine of the episodes were hospital-acquired, 56 episodes were associated with health care system exposure, and the remaining 37 episodes were classified as true community-acquired bacteremia. The characteristics of patients, primary site of infection, antimicrobial susceptibilities of S. aureus isolates, adequacy of initial antimicrobial therapy, and percentage of metastatic infections differed significantly between health care-associated and true community-acquired S. aureus bacteremias. Prevalence of MRSA infection in true community-acquired bacteremia was low in contrast to bacteremia with health care-associated exposure (2.7% versus 42.9%, P < 0.01). In conclusion, clinical characteristics and risk of contracting methicillin-resistant S. aureus bacteremia among community patients with and without exposure to health care system are distinct. Precise classification of patients is mandatory for the surveillance of antimicrobial resistance and selection of rationale empirical antibiotics.     

Teicoplanin in the treatment of infections by staphylococci, Clostridium difficile and other gram-positive bacteria

Eighty-three episodes of Gram-positive infection in 82 patients were treated with teicoplanin in an open study. Infectious episodes included endocarditis (6 cases), bacteraemia (7), osteomyelitis (8), pseudomembranous colitis (13), cellulitis (11), urinary tract infection (5), pneumonia (1), wound and post-surgical infections (9) and erysipelas (23). Four patients affected by an overwhelming Gram-positive infection as well as eight cases of Gram-positive-Gram-negative mixed infections received teicoplanin in combination with other antibiotics. The average duration of treatment was 16 days (range 5-70). In pseudomembranous colitis teicoplanin was given by mouth for ten days. Staphylococcus aureus (11 methicillin-sensitive and 13 methicillin-resistant strains) and Clostridium difficile (13 isolates) were the most frequent pathogens. Overall 89% (74/83) of the infections were cured, 3.6% (3/83) improved and 3.6% (3/83) failed. Relapse and superinfection were observed in 2.4% (2/83) and 1.2% (1/83) episodes respectively. All pseudomembranous colitis cases were clinically cured and C. difficile was eradicated in all but one patient. The MIC range, MIC50 and MIC90 (mg/l) of teicoplanin for C. difficile were less than 0.125-0.250, less than 0.125 and 0.250 respectively. Pharmacokinetic studies in patients given a single iv daily maintenance dose of 400 mg showed that the steady-state trough teicoplanin concentrations in serum were reached on day 8. Assays of skin-subcutaneous tissue biopsies showed that teicoplanin penetrated well into these structures. Side effects were observed in six of the 82 treated patients (7.3%) and teicoplanin had to be discontinued in four cases. The results of the study show that teicoplanin is a safe and useful new agent for the treatment of infections caused by Gram-positive organisms, including methicillin-resistant staphylococci and C. difficile.     

Timentin versus piperacillin or moxalactam in the therapy of acute bacterial infections.

In a randomized comparative study, 116 patients with acute bacterial infections were treated with timentin (ticarcillin plus clavulanic acid) or a comparative agent (piperacillin for respiratory or urinary tract infections, and moxalactam for soft tissue infections). There were 91 clinically evaluated infections (timentin, 46; piperacillin, 29; moxalactam, 16). Twelve patients were bacteremic. A satisfactory clinical response occurred in all 46 patients treated with timentin and in 42 of the 45 treated with a comparative agent. Two clinical failures were due to superinfection (a Staphylococcus aureus pneumonia in the piperacillin group and an enterococcal skin infection in the moxalactam group), and one clinical failure was due to a primary S. aureus skin infection (moxalactam group). One wound isolate of Pseudomonas aeruginosa developed resistance to timentin during therapy (despite clinical improvement). Adverse reactions were uncommon but did include one patient treated with timentin who developed unexplained hallucinations.     

Outcome of cephalosporin treatment of bacteremia due to CTX-M-type extended-spectrum beta-lactamase-producing Escherichia coli

The aim of the study was to analyze the outcome of different antibiotic treatments for bacteremia due to CTX-M-type extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. In a prospective controlled clinical study from October 2002 to April 2005, 22 consecutive cases of bacteremia due to ESBL-producing E. coli with a ceftazidime-inhibition zone diameter of > or =18 mm were studied. The Etest method was used to determine the MIC values of cefotaxime, ceftazidime, imipenem, gentamicin, and ciprofloxacin against 22 isolates of E. coli. The polymerase chain reaction and sequencing analyses were used to determine the genotypes of the ESBLs. Of these 22 episodes, 7 were treated with ceftazidime, 8 were treated with imipenem/cilastatin, and 7 were treated with cefoperazone/sulbactam after detection of bacteremia. The demographic characteristics were comparable between the 3 groups. The treatment success ratio was similar (ceftazidime 85.7%, imipenem/cilastatin 87.5%, cefoperazone/sulbactam 71.4%, P = 0.637). Difficulties arose during treatment of peritonitis caused by CTX-M-producing E. coli bacteremia. Patients with bacteremia associated with urinary tract infection or biliary tract infection had a better chance of survival. All the 22 strains of E. coli produced CTX-M ESBLs (CTX-M-3, CTX-M-14, or CTX-M-27). The MICs of ceftazidime for 22 strains of E. coli were < or =8 microg/mL. All 7 patients who received ceftazidime survived, 6 of them were cured. Treatment in one patient with a ceftazidime MIC of 2 mug/mL failed because of abdominal abscess. Treatment with ceftazidime in vivo was effective against cases of CTX-M ESBL-producing E. coli bacteremia due to urinary tract infections and biliary tract infection when the MICs of ceftazidime were < or =8 microg/mL.     

Evaluation of aztreonam in difficult-to-treat infections with prolonged posttreatment follow-up.

Aztreonam at doses of 1 or 2 g given intramuscularly or intravenously every 8 h for 7 to 42 days was given to 55 patients, most of them suffering from difficult-to-treat infections either because the isolated pathogens were multiresistant or because of the location of the infection. Infections included: urinary tract (23 cases), deep soft tissue phlegmon (12 cases), chronic osteomyelitis in exacerbation (7 cases), abscesses (7 cases), pneumonia (4 cases), and external otitis (2 cases). In culture specimens, Pseudomonas aeruginosa (24 isolates) and various Enterobacteriaceae species (37 isolates) were isolated with MICs ranging from 0.25 to 16 micrograms/ml. Clinically, at the completion of treatment and after a 6-week posttreatment follow-up, 45 (81.6%) patients were cured, 4 (7.2%) improved, 3 (5.6%) relapsed, and 3 (5.6%) failed to respond to therapy. Bacteriologically, at the end of treatment, the pathogen was eradicated in 50 patients (91%) and persisted in 5 (9%). After a 6-week follow-up, cultures remained sterile in 33 patients (60.0%), 16 (29.1%) relapsed, in 6 (10.9%) bacteria persisted, and superinfection was reported in 4 (7.3%) patients. No appreciable adverse effects or toxicity was observed. From the reported results, it is concluded that aztreonam is a valuable addition to the field of antimicrobial chemotherapy that can be used effectively and safely in the treatment of a variety of gram-negative infections.     

Effectiveness of antibiotic combination therapy as evaluated by the Break-point Checkerboard Plate method for multidrug-resistant Pseudomonas aeruginosa in clinical use

Multidrug-resistant Pseudomonas aeruginosa (MDRP) strains are defined as having resistance to the following 3 groups of antibiotics: carbapenems, aminoglycosides, and fluoroquinolones. Antibiotic combinations have demonstrated increased activity in vitro compared with a single agent. As an in vitro method of determining the combination activity of antibiotics, the Break-point Checkerboard Plate (BC-plate) can be used routinely in clinical microbiology laboratories. We evaluated the effectiveness of the BC-plate for MDRP infections in clinical settings.We retrospectively selected cases of MDRP infection treated with combination therapy of antibiotics in Tokyo Medical University Hospital (1015 beds), Tokyo, Japan, from November 2010 to October 2012.A total of 28 MDRP strains were clinically isolated from 28 patients during the study period. This study design is a case series of MDRP infection. Six infections among the 28 patients were treated based on the results of the BC-plate assay, and the 6 strains tested positive for MBL. One patient had pneumonia, 3 had urinary tract infections, 1 had vertebral osteomyelitis, and 1 had nasal abscess. The combination of aztreonam with amikacin demonstrated the most frequently recognized in vitro effect (5 patients). Next, aztreonam with ciprofloxacin and piperacillin with amikacin revealed equivalent in vitro effects (3 patients, respectively). The clinical cure rate was 83.3% (5/6 patients).Antibiotic combination therapy based on the results of the BC-plate assay might indicate the effective therapy against MDRP infection in clinical settings.     

Combination therapy with intravenous colistin for management of infections due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis

Colistin, an antibiotic almost abandoned for intravenous administration for many years due to its reported toxicity, has been recently reintroduced in clinical practice due to the emergence of multidrug-resistant gram-negative bacteria and the lack of development of new antibiotics to combat them. To assess the safety and effectiveness of intravenous colistin, in combination with other antimicrobial agents, in the treatment of serious infections in patients without cystic fibrosis, a retrospective cohort study in a 450-bed tertiary-care hospital in Athens, Greece, was performed. Patients who were hospitalized from 1 October 2000 to 31 January 2004 and received intravenous colistin for more than 72 h were further analyzed. The primary outcome measure was the in-hospital mortality; secondary end points were the clinical outcome of the infections and the occurrence of colistin toxicity. Fifty patients received intravenous colistin with a median (mean) daily dose of 3 (4.5) million IU for 16.5 (21.3) days for the management of 54 episodes of infections due to multidrug-resistant gram-negative bacteria. The predominant infections were pneumonia (33.3%), bacteremia (27.8%), urinary tract infection (11.1%), and intra-abdominal infection (11.1%). The responsible pathogens were Acinetobacter baumannii (51.9%), Pseudomonas aeruginosa (42.6%), and Klebsiella pneumoniae (3.7%) strains (no pathogen was isolated from one case). In-hospital mortality was 24% (12/50 patients). Clinical response (cure or improvement) of the infection was observed in 66.7% of episodes (36/54). In the studied group, serum creatinine levels were decreased, at the end of colistin treatment, by an average of 0.2 +/- 1.3 mg/dl compared to baseline levels. Deterioration of renal function during colistin therapy was observed in 4/50 patients (8%). Coadministration of other antimicrobial agents with spectrum against gram-negative microorganisms and the absence of a control group constitute the major limitations of this study. The use of intravenous colistin for the treatment of infections due to multidrug-resistant gram-negative bacteria appears to be safe and effective.     

Clinical trial of the efficacy and safety of ticarcillin and clavulanic acid

Forty-three hospitalized patients were treated with a new antibiotic combination containing ticarcillin plus the beta-lactamase inhibitor, clavulanic acid, in a fixed combination for intravenous use. A variety of infections were treated, including pneumonia, bacteremia, urinary tract infection, and osteomyelitis. Of 50 episodes of infection in 43 patients, 44 clinical cures were obtained, with 5 patients improving and 1 patient failing to respond to treatment. In vitro susceptibility testing of 101 clinical isolates was notable for the rarity of resistance to the combination antibiotic. Of specific interest, all 14 isolates of Staphylococcus aureus were susceptible to ticarcillin plus clavulanic acid, whereas only 2 of the 14 isolates were susceptible to ticarcillin alone. Adverse reactions to the study drug were minimal; eosinophilia, unaccompanied by other allergic phenomena, and oral candidiasis were most frequent. Overall, the combination of ticarcillin with the beta-lactamase inhibitor, clavulanic acid, appears to be a safe and effective drug for the treatment of infections caused by susceptible organisms.