Susceptibility Of Gram-negative Bacilli Research Articles

Efficacy and safety of antibiotics targeting Gram-negative bacteria in nosocomial pneumonia: a systematic review and Bayesian network meta-analysis

BackgroundMultiple randomized controlled studies have compared numerous antibiotic regimens, including new, recently commercialized antibiotics in the treatment of nosocomial pneumonia (NP). The objective of this Bayesian network meta-analysis (NMA) was to compare the efficacy and the safety of different antibiotic treatments for NP.MethodsWe conducted a systematic search of PubMed, Medline, Web of Science, EMBASE and the Cochrane Library databases from 2000 through 2021. The study selection included studies comparing antibiotics targeting Gram-negative bacilli in the setting of NP. The primary endpoint was 28 day mortality. Secondary outcomes were clinical cure, microbiological cure and adverse events.ResultsSixteen studies encompassing 4993 patients were included in this analysis comparing 13 antibiotic regimens. The level of evidence for mortality comparisons ranged from very low to moderate. No significant difference in 28 day mortality was found among all beta-lactam regimens. Only the combination of meropenem plus aerosolized colistin was associated with a significant decrease of mortality compared to using intravenous colistin alone (OR = 0.43; 95% credible interval [0.17–0.94]), based on the results of the smallest trial included. The clinical failure rate of ceftazidime was higher than meropenem with (OR = 1.97; 95% CrI [1.19–3.45]) or without aerosolized colistin (OR = 1.40; 95% CrI [1.00–2.01]), imipemen/cilastatin/relebactam (OR = 1.74; 95% CrI [1.03–2.90]) and ceftazidime/avibactam (OR = 1.48; 95% CrI [1.02–2.20]). For microbiological cure, no substantial difference between regimens was found, but ceftolozane/tazobactam had the highest probability of being superior to comparators. In safety analyses, there was no significant difference between treatments for the occurrence of adverse events, but acute kidney failure was more common in patients receiving intravenous colistin.ConclusionsThis network meta-analysis suggests that most antibiotic regimens, including new combinations and cefiderocol, have similar efficacy and safety in treating susceptible Gram-negative bacilli in NP. Further studies are necessary for NP caused by multidrug-resistant bacteria.Registration PROSPERO CRD42021226603

BACTERIAL ISOLATES OF THE RESPIRATORY TRACT INFECTION AND THEIR CURRENT SENSITIVITY PATTERN AMONG PATIENTS ADMITTED IN TERTIARY CARE HOSPITAL.

Background & Objectives: This study was aimed to observe the susceptibility pattern of bacterial isolates from respiratory tract infection (RTI). Respiratory tract infection is considered as one of the major public health problems and a leading cause of morbidity and mortality in many developing countries. Respiratory tract is the part of the human system that plays a vital role in breathing processes. In human, the respiratory system can be subdivided into an Upper respiratory tract and a Lower respiratory tract based on anatomical features. The respiratory tract is constantly exposed to microbes due to the extensive surface area. Methods: The present study was conducted retrospectively for a period of one year November 2021 to October 2022. All respiratory specimens included Sputum, BAL, throat swab; endotracheal aspirate specimens were collected aseptically from patients and cultured on the appropriate bacteriological media (Blood agar, MacConkey agar & Chocolate Agar). Bacterial isolates were identified by biochemical tests and antimicrobial susceptibility performed by standard methods as per CLSI 2022. Results: 152 (72.3%) of total 210 samples were positive for bacterial culture. 126 (82.8%) were gram negative bacilli (GNB) and 26 (17.1%) were gram positive cocci (GPC). The predominant pathogen isolated was K. pneumoniae 46 (30.2%) followed by Escherichia coli 28 (18.4%).The overall susceptibility of GNB was highest towards Imipenem, Meropenem followed by Piperacillin tazobactam and Amikacin. Gram positive organisms exhibited highest susceptibility towards Vancomycin and Linezolid. Conclusion: Imipenem is the most sensitive antibiotic followed by Piperacillin tazobactam and Amikacin which can be used for empirical therapy for respiratory tract infections (RTI). The antibiotic therapy should be modified as per the culture and sensitivity report. Regular determinations of the type of bacterial pathogens and updation of antibiogram must be followed in every institution to aid in better patient management by helping the clinician in the judicious use of antibiotics.

Phenotypic characterization of carbapenem non-susceptible gram-negative bacilli isolated from clinical specimens.

BackgroundMultidrug resistant, extremely drug-resistant, pan-drug resistant, carbapenem-resistant, and carbapenemase-producing gram-negative bacteria are becoming more common in health care settings and are posing a growing threat to public health.ObjectiveThe study was aimed to detect and phenotypically characterize carbapenem no- susceptible gram-negative bacilli at the Ethiopian Public Health Institute.Materials and methodsA prospective cross-sectional study was conducted from June 30, 2019, to May 30, 2020, at the national reference laboratory of the Ethiopian Public Health Institute. Clinical samples were collected, inoculated, and incubated for each sample in accordance with standard protocol. Antimicrobial susceptibility testing was conducted using Kirby-Bauer disk diffusion method. Identification was done using the traditional biochemical method. Multidrug-resistant and extensively drug-resistant isolates were classified using a standardized definition established by the European Centre for Disease Prevention and Control and the United States Centers for Disease Prevention and Control. Gram-negative organisms with reduced susceptibility to carbapenem antibiotics were considered candidate carbapenemase producers and subjected to modified carbapenem inactivation and simplified carbapenem inactivation methods. Meropenem with EDTA was used to differentiate metallo-β-lactamase (MBL) from serine carbapenemase. Meropenem (MRP)/meropenem + phenylboronic acid (MBO) were used to differentiate Klebsiella pneumoniae carbapenemase (KPC) from other serine carbapenemase producing gram-negative organisms.ResultsA total of 1,337 clinical specimens were analyzed, of which 429 gram-negative bacterial isolates were recovered. Out of 429 isolates, 319, 74, and 36 were Enterobacterales, Acinetobacter species, and Pseudomonas aeruginosa respectively. In our study, the prevalence of multidrug-resistant, extensively drug-resistant, carbapenemase-producing, and carbapenem nonsusceptible gram-negative bacilli were 45.2%, 7.7%, 5.4%, and 15.4% respectively. Out of 429 isolates, 66 demonstrated reduced susceptibility to the antibiotics meropenem and imipenem. These isolates were tested for carbapenemase production of which 34.8% (23/66) were carbapenemase producers. Out of 23 carbapenemase positive gram-negative bacteria, ten (10) and thirteen (13) were metallo-beta-lactamase and serine carbapenemase respectively. Three of 13 serine carbapenemase positive organisms were Klebsiella pneumoniae carbapenemase.ConclusionThis study revealed an alarming level of antimicrobial resistance (AMR), with a high prevalence of multidrug-resistant (MDR) and extremely drug-resistant, carbapenemase-producing gram-negative bacteria, particularly among intensive care unit patients at the health facility level. These findings point to a scenario in which clinical management of infected patients becomes increasingly difficult and necessitates the use of “last-resort” antimicrobials likely exacerbating the magnitude of the global AMR crisis. This mandates robust AMR monitoring and an infection prevention and control program.

Association between fluoroquinolone utilization rates and susceptibilities of gram-negative bacilli: Results from an 8-year intervention by an antibiotic stewardship program in an inner-city United States hospital.

This study evaluated an antibiotic stewardship program (ASP) intervention aimed at reducing inpatient fluoroquinolone (FQ) use and examined its impact on ciprofloxacin susceptibilities of gram-negative bacteria in a large 611-bed community hospital. A two-step ASP intervention was implemented: an electronic medical record algorithm that prompted physicians to re-evaluate FQ use shortly after admission and changed institutional UTI/pneumonia guidelines that recommended options alternate to FQs for first-line empiric antibiotic therapy in 2010 and 2011 respectively. Between 2007 and 2017 FQ use and ciprofloxacin susceptibilities of all non-duplicate cultured isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa obtained ≥72 h after admission were reviewed. Ambulatory care isolates served as a comparison group. FQ utilization rates and relationships to ciprofloxacin susceptibility were evaluated using interrupted time series models. Over the 11-year period, FQ use decreased from 110.0 (2007) to 26.2 (2017) days of therapy/1000 days at risk (p < 0.001). Compared to pre-intervention, the estimated (post-intervention) reduction in FQ utilization was 28.4 (95% CI: 10.9-46) days of therapy/1000 days at risk. Reduced FQ utilization was correlated with increase susceptibilities to ciprofloxacin of hospital onset isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis (p < 0.02), and Pseudomonas aeruginosa (p = 0.07). No significant susceptibility change was observed in the ambulatory care isolates. Persuasive interventions by an ASP successfully modified physicians' inpatient empiric antibiotic use, produced a sustained reduction in FQ utilization rates and increased ciprofloxacin susceptibility to four commonly encountered gram-negative bacteria in a community hospital.

Bacteriological profile and antibiotic susceptibility patterns of lower respiratory tract infections in a tertiary care hospital, Central Kerala

Background and Objective: Lower respiratory tract infections (LRTIs) is one of the leading human diseases causing high morbidity and mortality worldwide. The prevalent etiological agents and their antimicrobial resistance patterns differs, both geographically and over time. With emerging resistance of respiratory bacterial pathogens to commonly used antibiotics, it is imperative to study their recent trends for effective management of these cases. Materials and Methods: A retrospective, record based study was conducted on culture and sensitivity reports of lower respiratory samples obtained in the microbiology lab during 1st January 2015- 31st December 2017. The samples were processed by standard methods for isolation and identification followed by antimicrobial sensitivity testing using Kirby Bauer disc diffusion method. Results: 288 (26.34%) of total 1093 samples were positive for bacterial culture. 244 (84.7%) were gram negative bacilli (GNB) and 44 (15.3%) were gram positive cocci. The predominant pathogen isolated was K.pneumoniae (31.1%) followed by P.aeruginosa (30.2%).The overall susceptibility of GNB was highest towards Imipenem followed by Amikacin and Piperacillin tazobactam with resistance rates of 11.5%, 26.2% and 31.6% respectively. Gram positive organisms exhibited highest susceptibility towards Vancomycin and Linezolid. 15.4 % of Staphylococcus aureus were Methicillin resistant (MRSA). Conclusion: Imipenem is the most sensitive antibiotic followed by Amikacin and Piperacillin tazobactam which can be used for empirical therapy for LRTI. The antibiotic therapy should be modified as per the culture and sensitivity report. Regular determinations of the type of bacterial pathogens and updation of antibiogram must be followed in every institution to aid in better patient management by helping the clinician in the judicious use of antibiotics. Keywords: Antibiotic resistance patterns, Lower respiratory tract infections.

Risk Factors for the Antibiotic Resistant Gram-Negative Bacilli Associated Infections in Burn Patients and the In-Vitro Susceptibility of Colistin

Background: Burns patients are predisposed to infectious complications. Amongst microbial infections, Gram-negative bacilli are the most prevalent bacteria in the burn units. Objectives: The current study aimed to identify the risk factors associated with antibiotic-resistant Gram-negative bacilli in hospitalized burn patients and determine the in-vitro susceptibility of these organisms to colistin. Methods: Two hundred burn patients hospitalized in the burn unit and ICU burn ward were allocated to two groups (each with 100 patients) of patients with antibiotic-resistant Gram-negative bacilli infections and the other with antibiotic susceptible Gram-negative bacilli associated infections. The susceptibility of Gram-negative bacilli was done towards various antibacterial agents by the Kirby-Bauer method. Susceptibility of colistin was performed using both E-test and disc diffusion methods. Results: The history of antibiotic usage, length of ICU stay, mechanical ventilation, and catheter usage were the most important risk factors for infections associated with antibiotic-resistant Gram-negative bacilli. Pseudomonas aeruginosa and Acinetobacter baumannii were the most prevalent bacteria in the burn unit. Only one A. baumannii isolate was found resistant toward colistin by both disk diffusion and E-test methods. Conclusions: Burn patients are prone to infections, and Gram-negative bacilli predominates in patients harboring risk factors. These findings influence the choice of traditional therapeutic regimens in such patients. Colistin served as an appropriate antibiotic choice.

Risk factors for and clinical outcomes of carbapenem non-susceptible gram negative bacilli bacteremia in patients with acute myelogenous leukemia

BackgroundCarbapenem is frequently used when gram negative bacilli (GNB) bacteremia is detected especially in neutropenic patients. Consequently, appropriate treatment could be delayed in GNB bacteremia cases involving organisms which are not susceptible to carbapenem (carba-NS), resulting in a poor clinical outcomes. Here, we explored risk factors for carba-NS GNB bacteremia and its clinical outcomes in patients with acute myelogenous leukemia (AML) that underwent chemotherapy.MethodsWe reviewed all GNB bacteremia cases that occurred during induction or consolidation chemotherapy, over a 15-year period, in a tertiary-care hospital.ResultsAmong 489 GNB bacteremia cases from 324 patients, 45 (9.2%) were carba-NS and 444 (90.8%) were carbapenem susceptible GNB. Independent risk factors for carba-NS GNB bacteremia were: carbapenem use at bacteremia onset (adjusted odds ratio [aOR]: 91.2; 95% confidence interval [95%CI]: 29.3–284.1; P < 0.001); isolation of carbapenem-resistant Acinetobacter baumannii (aOR: 19.4, 95%CI: 3.4–112.5; P = 0.001) in the prior year; and days from chemotherapy to GNB bacteremia (aOR: 1.1 per day, 95%CI: 1.1–1.2; P < 0.001). Carba-NS bacteremia was independently associated with in-hospital mortality (aOR: 6.6, 95%CI: 3.0–14.8; P < 0.001).ConslusionCarba-NS organisms should be considered for antibiotic selection in AML patients having these risk factors.

Impact of Baseline Characteristics on Future Episodes of Bloodstream Infections: Multistate Model in Septic Patients With Bloodstream Infections.

Looking only at the index infection, studies have described risk factors for infections caused by resistant bacteria. We hypothesized that septic patients with bloodstream infections may transition across states characterized by different microbiology and that their trajectory is not uniform. We also hypothesized that baseline risk factors may influence subsequent blood culture results. All adult septic patients with positive blood cultures over a 7-year period were included in the study. Baseline risk factors were recorded. We followed all survivors longitudinally and recorded subsequent blood culture results. We separated states into bacteremia caused by gram-positive cocci, susceptible gram-negative bacilli (sGNB), resistant GNB (rGNB), and Candida spp. Detrimental transitions were considered when transitioning to a culture with a higher mortality risk (rGNB and Candida spp.). A multistate Markov-like model was used to determine risk factors associated with detrimental transitions. A total of 990 patients survived and experienced at least 1 transition, with a total of 4282 transitions. Inappropriate antibiotics, previous antibiotic exposure, and index bloodstream infection caused by either rGNB or Candida spp. were associated with detrimental transitions. Double antibiotic therapy (beta-lactam plus either an aminoglycoside or a fluoroquinolone) protected against detrimental transitions. Baseline characteristics that include prescribed antibiotics can identify patients at risk for subsequent bloodstream infections caused by resistant bacteria. By altering the initial treatment, we could potentially influence future bacteremic states.

Susceptibilities of Gram-negative bacilli from hospital- and community-acquired intra-abdominal and urinary tract infections: a 2016-2017 update of the Chinese SMART study.

Objectives: To update the epidemiology and susceptibility of hospital-acquired (HA) and community-acquired (CA), as well as intensive care unit (ICU) vs non-ICU-derived intra-abdominal infection (IAI) and urinary tract infection (UTI) pathogens in Chinese hospitals.Methods: A total of 2,546 Gram-negative isolates from IAIs and 1,947 isolates from UTIs collected in 16 hospitals and 7 regions of China from 2016 to 2017 were analyzed.Results: E. coli and K. pneumoniae were the most common pathogens identified in HA (40.7%, 21.9%) and CA (49.2%, 21.3%) IAIs and in HA (59.0%, 17.3%) and CA (64.3%, 12.7%) UTIs, respectively. The overall rates of extended-spectrum β-lactamase (ESBL)-positive strains were 48.2% for E. coli and 26.4% for K. pneumoniae. The rates of ESBL-positive E. coli and K. pneumoniae strains were significantly higher in HA than in CA IAIs (51.7% vs 42.4%, P=0.016 and 22.0% vs 20.6%, P<0.001). IAI E. coli ESBL-producing isolates were most susceptible to IPM (97.2%) and AMK (93.9%), and UTI-associated E. coli ESBL-producers were 94.74% susceptible to amikacin (AMK), 97.02% to imipenem (IPM), and 91.4% to ertapenem (ETP). IAI K. pneumoniae ESBL-producing isolates were most susceptible to AMK (84.43%) and IPM (82.79%), and UTI-associated K. pneumoniae ESBL-producers were 88.39% susceptible to AMK, 87.5% to IPM, and 82.14% to ETP. Overall, percentages of susceptible strains to ETP, IPM, AMK, and Piperacillin-Tazobactam (TZP) were in the range of 82.0% to 96.4%, to 5 cephalosporins in the range of 31.4%-69.6% and to 2 fluoroquinolones in the range of 37.8%-45.5% for E. coli and 65.5%-90.7%, 37.7%-75.3%, and 43.9%-73.2% for K. pneumoniae, respectively.Conclusion: E. coli and K. pneumoniae continued to be the main pathogens in Chinese UTIs and IAIs with high ESBL-positive rates between 2016 and 2017. Carbapenem- or amikacin-based therapies were the most effective to combat IAI and UTI pathogens.

Predicting resistant etiology in hospitalized patients with blood cultures positive for Gram-negative bacilli

ObjectiveTo develop a risk-scoring tool to predict multidrug-resistant (MDR) etiology in patients with bloodstream infections (BSI) caused by Gram-negative bacilli (GNB). MethodsA prospective multicenter study analyzed patients with BSI hospitalized in 31 Internal Medicine wards in Italy from March 2012 to December 2012. Patients with BSI caused by MDR-GNB (non-susceptible to at least one agent in three antimicrobial categories) were compared to those with BSI due to susceptible GNB. A logistic regression to identify predictive factors of MDR-GNB was performed and the odds ratio (OR) were calculated. A score to predict the risk of MDR was developed. ResultsOf 533 BSI episodes, 253 (47.5%) were caused by GNB. Among GNB-BSI, 122 (48.2%) were caused by MDR-GNB while 131 (51.8%) by non-MDR GNB. At multivariate analysis transfer from long-term care facility (OR 9.013, 95% CI 1.089–74.579, p = 0.041), hospitalization in the last 3 months (OR 2.882, 95% CI 1.580–5.259, p = 0.001), urinary catheter (OR 2.315, 95% CI 1.202–4.459, p = 0.012), antibiotic therapy in the last 3 months (OR 1.882, 95% CI 1.041–3.405, p = 0.036), age ≥ 75 years (OR 1.866, 95% CI 1.076–3.237, p = 0.026) were factors independently associated with MDR etiology. A score ranging from 0 to 10 was useful to recognize patients at lowest risk (0 points: Negative Likelihood Ratio 0.10) and those at highest risk (>6 points, Positive Likelihood Ratio 11.8) of GNB bacteremia due to a MDR strain. ConclusionsSpecific predictors of MDR etiology are useful to calculate probabilities of MDR etiology among hospitalized patients with blood cultures positive for GNB.

Evaluation of antimicrobial susceptibility of gram negative bacilli isolated from nosocomial infection in general hospital Tehran, Iran 2011

Evaluation of antimicrobial susceptibility of gram negative bacilli isolated from nosocomial infection in general hospital Tehran, Iran 2011

Inhaled colistin as monotherapy for multidrug-resistant gram (−) nosocomial pneumonia: A case series

Reports of patients with polymyxin-only susceptible gram-negative nosocomial pneumonia treated with inhaled, but without concurrent intravenous, colistin are rare. Patients admitted in a tertiary 450-bed tertiary care centre during the period 05/01/2005-05/31/2007 and receiving colistin through nebulization, but not systemically, were included in this retrospective case series. Five patients (three with ventilator-associated pneumonia and two with nosocomial pneumonia) received colistin through nebulization without concomitant intravenous colistin. The isolated pathogens were Acinetobacter baumannii (three cases), Pseudomonas aeruginosa (one case) and the combination of Klebsiella pneumoniae, A. baumannii and P. aeruginosa (one case). They were susceptible only to colistin (three cases) or to colistin and gentamicin (two cases). Intravenous antimicrobial agents given concurrently were piperacillin/tazobactam, meropenem, ceftriaxone and ciprofloxacin; isolated pathogens were resistant to these agents. Four (80%) out of the five patients were cured, survived and were discharged. One patient died. No colistin-related adverse event was observed. The experience from this case series and other relevant recent reports suggest that treatment of pneumonia due to polymyxin-only susceptible gram-negative bacilli with inhaled colistin (without concurrent systemic administration) deserves further careful investigation.

Incidence of antibiotic resistance in blood and urine isolates from hospitalized patients. Report from a European collaborative study. European Study Group on Antibiotic Resistance (ESGAR).

During 1992-93, 2544 isolates from blood cultures, comprising 52% gram-negative bacilli, 24% Staphylococcus aureus, 15% other staphylococci, 7% Enterococcus faecalis and 2% E. faecium, were consecutively collected and identified in 30 laboratories in 21 European countries. In addition 2512 urine isolates, comprising 82% gram-negative bacilli, 3% S. aureus, 4% other staphylococci and 11% enterococci were collected. The bacteria were sent to 3 laboratories for susceptibility testing by the microdilution method in Mueller-Hinton broth. The MICs of penicillins and aztreonam for all susceptible gram-negative bacilli were 0.25-8 mg/l, penems 0.032-2 mg/l, cefotaxime, ceftazidime and cefpirome or cefepime 0.032-0.25 mg/l, gentamicin, tobramycin and netilmicin 0.125-2 mg/l, amikacin 0.5-4 mg/l, ciprofloxacin 0.016-1 mg/l, trimethoprim 0.25-1 mg/l and tetracycline 1-2 mg/l. For susceptible staphylococci the MICs of erythromycin were 0.25-0.5 mg/l, clindamycin 0.125-0.25 mg/l, methicillin 2-8 mg/l, vancomycin and trimethoprim 1-4 mg/l, ciprofloxacin 0.25-1 mg/l, gentamicin and tobramycin 0.25-1 mg/l. For the enterococci the MICs of ampicillin and vancomycin were 2-4 mg/l and of imipenem, teicoplanin and trimethoprim 0.5-1 mg/l. The antibiotic resistance rates varied between laboratories, being lower in northern Europe, except for the penems, cefpirome and cefepime, which showed uniformly lower resistance rates. Compared to the earlier European studies the resistance rates to beta-lactam antibiotics among the gram-negatives have not changed except with an increase to cefotaxime and ceftazidime in central Europe. Resistance to aminoglycosides had also increased in central Europe from 7-8% to 20-21%, but decreased in southern Europe from 22-24% to 13-14% among the blood isolates and from 12-28% to 6-7% among the urine isolates. There was an increase in resistance to ciprofloxacin and gentamicin in staphylococci from southern Europe. The prevalence of MRSA was significant in central and southern Europe. It is of importance that collaborative national and international studies on the incidence of antibiotic resistance are being performed on a repetitive basis.

Comparison of fixed concentration and fixed ratio options for testing susceptibility of gram-negative bacilli to piperacillin and piperacillin/tazobactam.

Piperacillin combined with tazobactam was tested at both a fixed ratio (8:1) and fixed tazobactam concentration (4 micrograms/ml) against 2,685 consecutively isolated gram-negative bacilli and 56 highly piperacillin-resistant isolates. Tazobactam significantly enhanced the spectrum of piperacillin activity. Overall, at a concentration of 16 micrograms/ml piperacillin alone inhibited 78.8% of the Enterobacteriaceae isolates compared to inhibition of 92.7% and 95.5% by the 8:1 ratio and fixed (4 micrograms/ml) tazobactam combinations, respectively. In MIC tests the two combination options performed comparably against both routine and highly piperacillin-resistant isolates. Synergistic inhibition was observed for comparable numbers of isolates with the two combination options, the most marked effect being seen in the more highly piperacillin-resistant isolates. Both testing options are supported by the available human pharmacokinetic data; however the 8:1 ratio of piperacillin to tazobactam may be preferable given that the clinical formulation contains the two compounds in an 8:1 ratio and this ratio is maintained in vivo.

Efficacy and Safety of Low-Dose Aztreonam in the Treatment of Moderate to Severe Infections Due to Gram-Negative Bacilli

One hundred fifty-three patients with moderate to severe infections due to gram-negative bacilli, including septicemia (60 cases), lower respiratory tract infection (32 cases), intraabdominal 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 in the study included documented infection due to gram-negative bacilli and a measurement of severity of disease of less than 12 (as defined by a Simplified Acute Physiology Score for the 115 cases of community-acquired infection). Other than aztreonam, no antibiotic active against gram-negative bacilli was allowed to be used for treatment. Seventy-one patients in whom gram-positive or anaerobic organisms were detected or suspected were given additional agents effective against the organisms. One hundred forty-one patients (92.2%) were cured; the mean duration of treatment was 10.9 +/- 4.0 days. None of the gram-negative bacilli initially isolated became resistant to aztreonam. Colonization, generally by a gram-positive organism, was observed in 27 patients and superinfection was observed in five. Aztreonam was well tolerated. This study suggests that a dosage of 2 g daily of aztreonam should be appropriate in the treatment of moderate to severe infections due to susceptible gram-negative bacilli.

Evolution of antibiotic therapy for infection in neutropenic patients: studies at M. D. Anderson Hospital.

The prompt administration of antibiotics as therapy for fever in neutropenic patients has become an accepted principle. Combinations of an aminoglycoside plus a broad-spectrum beta-lactam agent have been used most extensively, producing response rates of 65%-70% at M. D. Anderson Cancer Center, Houston, Texas. We found that in neutropenic patients aminoglycosides alone were not effective, even against infections caused by susceptible gram-negative bacilli. Among patients with neutrophil counts of less than 100/mm3, only approximately 25% responded. The first studies of combinations of a penicillin plus a cephalosporin were initiated at this institution. Carbenicillin plus cephalothin was as effective as carbenicillin plus kanamycin (57% vs. 56%), and moxalactam plus ticarcillin was as effective as moxalactam plus tobramycin (63% vs. 53%). Monotherapy with broad-spectrum beta-lactam agents has also been effective, even for the treatment of gram-negative bacillary infections, with response rates of 73%-100%. Recent prospective, randomized trials indicate that agents such as ceftazidime and aztreonam are as effective alone as in combination with an aminoglycoside or another beta-lactam antibiotic. Because of the changing spectrum of infecting organisms, of new approaches to therapy for malignant diseases that alter patients' susceptibility to infection, and of the availability of new antimicrobial agents, antibiotic therapy for fever in neutropenic patients will continue to be a subject for clinical investigation.

Evaluation of the in vitro susceptibility of gram-negative bacilli to cefotaxime, over a period of 3 years.

Cefotaxime is a third generation cephalosporin with a broad antimicrobial spectrum which includes the Enterobacteriaceae, some strains of Pseudomonas aeruginosa, Neisseria gonorrhoeae, N. meningitidis, Haemophilus spp., a high percentage of anaerobic micro-organisms and some strains of non-fermenting Gram-negative bacilli (Guzman et al. 1984; Jones & Thornsberry 1982). It has a marked resistance to the action of the (3lactamases of Gram-negative bacilli (Fu & Neu 1978). The purpose of this study was to evaluate the susceptibility of Gram-negative bacilli to cefotaxime. Computerised records of the susceptibility of micro-organisms isolated from hospitalised patients and outpatients from 1983 to 1986 were reviewed.

Susceptibility to beta-lactam antibiotics in septicemia isolates from twenty-nine European laboratories

In 1984 the European Study Group on Antibiotic Resistance (ESGAR) consecutively collected gram-negative bacilli and staphylococci blood isolates and performed susceptibility testing with 11 antibiotics using the microdilution method. In all 2,578 isolates were collected: 68% gram-negative bacilli and 32% staphylococci. The MICs of ampicillin and cefazoline for the susceptible gram-negative bacilli were 1-8 micrograms/ml; of piperacillin less than or equal to 0.5-4; of Sch 34343, cefotaxime, moxalactam, ceftazidime and aztreonam less than or equal to 0.5-2 micrograms/ml; of cefoxitin, cefuroxime and cefamandole less than or equal to 0.5-8 micrograms/ml. For susceptible staphylococci the MICs of cefazoline and cefuroxime were less than or equal to 0.5-1 micrograms/ml, and of cefoxitin, moxalactam, ceftazidime and cefotaxime, less than or equal to 0.5-32 micrograms/ml. The resistance levels varied between laboratories and countries, being lower in Northern Europe. In clinical protocols on patients with gram-negative septicemia from whom cefazoline-resistant strains were isolated, cefotaxime was the beta-lactam most commonly used (12%). In protocols on patients with staphylococcal septicemia from whom gentamicin-resistant or cefazoline-resistant strains were isolated, the most commonly used beta-lactam was cloxacillin (6%).

Summary of Worldwide Clinical Trials of Aztreonam in Patients with Lower Respiratory Tract Infections

Aztreonam was administered to 226 patients with lower respiratory tract infections--primarily pneumonia (181 patients)--due to gram-negative bacilli. The clinical response rate was 93%, and the microbiologic cure rate was 78%. Most patients received 1-g or 2-g intravenous doses of aztreonam three times daily for at least five days. Ninety-eight of the 226 patients were involved in a randomized comparison of aztreonam with tobramycin; the latter drug was administered to a group of 34 patients. The overall microbiologic cure rates for the two drugs were 86% and 71%, respectively. Aztreonam is effective for the treatment of lower respiratory tract infections due to susceptible gram-negative bacilli.

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.