In vitro synergy and selection of resistance by fluoroquinolones plus amikacin or beta-lactams against extended-spectrum beta-lactamase-producing Escherichia coli

This study compared the potential synergy of levofloxacin and ciprofloxacin in combination with cefepime, ceftazidime, imipenem, piperacillin/tazobactam or amikacin, against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli by using checkerboard and time kill studies. Moreover, selection of resistance was determined by frequency of mutations and by calculating the increase in minimum inhibitory concentrations (MICs) after five serial subcultures on antibiotic-containing plates. Synergy occurred more often with levofloxacin combined with imipenem (7/10 strains) and with levofloxacin or ciprofloxacin with amikacin (10/10) than for the other combinations. Time kill studies showed synergy for levofloxacin combined with amikacin, ceftazidime, imipenem or piperacillin/tazobactam, and for ciprofloxacin combined with amikacin, cefepime or imipenem. Antibiotic combinations selected for resistance less frequently than antibiotics alone. Mutation frequency was <10(-12) for all combinations. In conclusion, the combination of a fluoroquinolone with a beta-lactam or amikacin may provide improved antimicrobial activity and help limit the occurrence of resistance in ESBL-producing E. coli strains.     

Comparative antimicrobial potency of meropenem tested against Gram-negative bacilli: report from the MYSTIC surveillance program in the United States (2004)

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal resistance surveillance network of more than 100 medical centers worldwide monitoring the susceptibility of bacterial pathogens to carbapenems and other broad-spectrum agents. In 2004 (year six), the antimicrobial activity of 12 broad-spectrum agents was assessed against 2,799 Gram-negative bacterial isolates submitted from 15 United States (USA) medical centers using Clinical and Laboratory Standards Institute (CLSI; formerly NCCLS) recommended methods. Meropenem continued to demonstrate a high potency with MIC90 values 4- to 32-fold lower than imipenem against the Enterobacteriaceae. The wide spectrum of activity for meropenem against all Gram-negative isolates was demonstrated by the overall rank order of percentage susceptibility at CLSI breakpoints: amikacin (96.5%) > meropenem (96.0%) > imipenem (95.8%) > piperacillin/tazobactam (91.5%) > tobramycin (91.4%) > cefepime (91.2%) > ceftazidime (89.0%) > gentamicin (88.0%) > aztreonam (81.5%) > levofloxacin (80.5%) > ciprofloxacin (80.2%) > ceftriaxone (69.1%). Only the aminoglycosides (84.5%) and carbapenems (76.1-83.8%) exhibited acceptable levels of susceptibility against the Acinetobacter spp. isolates as this species group became more resistant to all antimicrobial classes. A continued increase in the resistance rate for both ciprofloxacin and levofloxacin over the six years was observed, most alarming among Escherichia coli (20.2-20.7%) and indole-positive Proteus species (34.4-42.2%) isolates, some documented as clonal. Continued surveillance of these broad-spectrum antimicrobial agents appears warranted to monitor the potency and spectrum of activity against Gram-negative pathogens causing serious infections and the emergence of new or novel resistance mechanisms that could compromise carbapenem therapy.     

Susceptibility of 228 Non-fermenting Gram-Negative Rods to Tigecycline and Six Other Antimicrobial Drugs

Abstract

The aim of the study was to determine the in vitro activity of tigecycline and 6 other antimicrobial drugs used in clinical practice against 228 clinical isolates of nonfermenting Gram-negative rods (NFGNRs) including Acinetobacter spp. Stenotrophomonas maltophilia, and Pseudomonas aeruginosa. Minimum inhibitory concentrations (MICs) were determined according to the recommendations of the Clinical and laboratory Standards institute. For tigecycline, we used the criteria approved by the FDA. Almost 50% of the clinical isolates of Acinetobacter spp. were resistant to piperacillin/tazobactam, ciprofloxacin, gentamicin, and ceftazidime. Strains of this microorganism were more susceptible to imipenem, and even more susceptible to colistin and tigecycline; no strains were resistant to tigecycline. Stenotrophomonas maltophilia showed even greater resistance to the drugs tested. Thus, all strains were resistant to imipenem and a large percentage (82.6%) were resistant to piperacillin/tazobactam. Resistance to the other agents tested was also high, with the exception of tigecycline, with only 3 resistant strains (MIC <8 mg/ml). Tigecycline, on the other hand, was scarcely active against Pseudomonas aeruginosa, which bears efflux pump systems such as MexXY-OprM. Almost 90% of strains were resistant to ciprofloxacin; only 8% were resistant to gentamicin; over half were colistin-intermediate or -resistant, and finally, approximately half of the strains were susceptible to the 3 beta-lactams studied. In conclusion, NFGNRs present variable susceptibility patterns, although they are generally highly resistant to antimicrobial agents including those considered more specific. Tigecycline, which showed good activity against most of the strains examined, broadens the spectrum of drugs available for the treatment of infections caused by these complex microorganisms.     

Tigecycline: a critical update

Tigecycline is the first Food and Drug Administration (FDA) approved glycylcycline antibiotic. It has shown remarkable in vitro activity against a wide variety of gram-positive, gram-negative and anaerobic bacteria including many multidrug resistant (MDR) strains. However, it has minimal activity against Pseudomonas aeruginosa and Proteus spp. To date, little resistance to tigecycline has been reported. Clinical trials studying complicated skin and skin-structure infections (cSSSIs) demonstrated that tigecycline has equivalent efficacy and safety compared with the combination of vancomycin and aztreonam. For complicated intra-abdominal infections (cIAIs), tigecycline was found to be as effective as imipenem/cilastatin. Adverse events related to tigecycline therapy, i.e. nausea and vomiting, were tolerable. Currently available data suggest that tigecycline may play an important role in the future as a monotherapy alternative to older broad-spectrum antibiotics, such as advanced generation cephalosporins, carbapenems, fluoroquinolones, piperacillin/tazobactam, and gram-positive directed agents (e.g. daptomycin, linezolid and quinupristin/dalfopristin) for which resistance is being increasingly reported from all parts of the world.     

In Vitro Activity of Meropenem against Ciprofloxacin-Resistant Enterobacteriaceae and Pseudomonas aeruginosa

Abstract

The in-vitro susceptibilities of a total of 174 ciprofloxacin-resistant Enterobacteriaceae and Pseudomonas aeruginosa were determined. According to the BSAC and NCCLS breakpoints, meropenem, aztreonam, ceftibuten, ceftazidime, imipenem and cefotaxime were the most active (>90%) antimicrobial agents tested against Enterobacteriaceae. Susceptibility of these strains to piperacillin/tazobactam, cefpodoxime and cefixime (84.96%) was higher than that to tobramycin, gentamicin and fosfomycin (50-75%). More than 90% of P. aeruginosa were susceptible to meropenem when both interpretative susceptibility breakpoint criteria were used. Piperacillin, piperacillin/tazobactam and ceftazidime were active against 50-75% of the same strains. Meropenem was the most active antimicrobial tested against all ciprofloxacin-resistant clinical isolates assayed.     

An observational study on the epidemiology of respiratory tract bacterial pathogens and their susceptibility to four injectable beta-lactam antibiotics: piperacillin, piperacillin/tazobactam, ceftazidime and ceftriaxone

Bacterial infections of the respiratory tract account for a large proportion of total medical consultations in general practice. In recent years, antibiotic resistance has increased alarmingly in a number of bacterial species that are common causes of these infections. The aim of this observational study was to determine the antibiotic resistance of microbial agents isolated from patients with acute or acutely exacerbated respiratory infections. Subjects recruited as potential sources of bacteria were either outpatients seen in a number of specialized clinics and hospital practices, or hospitalized patients. Overall, 648 consecutive patients (67% male, mean age 48.1+/-27.0 years) with infection of the upper or lower respiratory tract were observed during a 13-month period. A total of 551 pathogenic microbial strains were isolated and tested for their in vitro susceptibility to piperacillin, piperacillin/tazobactam, ceftazidime, and ceftriaxone. Among all isolates, the four most frequent pathogens were Pseudomonas aeruginosa (132 isolates, 24%), Streptococcus pyogenes (99 isolates, 18%), Staphylococcus aureus (93 isolates, 17%), and Klebsiella pneumoniae (46 isolates, 8%). The susceptibility of gram-positive isolates ranged from 97.5% to 95.1%, and no remarkable difference was found in the antibacterial activity of tested b-lactam antibiotics. The susceptibility of gram-negative isolates to piperacillin and piperacillin/tazobactam was also similar: 96.5% and 97.1%, respectively. In contrast, differences were found between piperacillin (or piperacillin/tazobactam) and either ceftazidime (p=0.003) or ceftriaxone (p<0.0003) in gram-negative isolates. We conclude that, despite the extensive use of beta-lactam antibiotics (piperacillin, ceftazidime, and ceftriaxone) in medical practice during the past three decades, the susceptibility of the most common pathogens involved in the etiology of upper and lower respiratory tract infections to these antibiotics is still high. In particular, bacterial resistance developed by gram-positive organisms against piperacillin is negligible and not alarming.     

白血病化疗后粒细胞缺乏伴真菌感染患者抗菌药物的应用研究

目的 探究白血病化疗后粒细胞缺乏伴真菌感染患者抗菌药物的使用情况,为临床制定合理使用抗生素方案提供参考依据.方法 回顾性分析淄博市中心医院收治的110例白血病化疗后粒细胞缺乏伴真菌感染患者的一般资料,采用该院自制的白血病化疗后粒细胞缺乏伴真菌感染患者抗菌药物使用情况调查表进行统计,最后根据统计结果进行分析.结果 110例患者中感染部位主要为呼吸道(47.27％)、其次为口腔或消化道(32.73％);通过经验性用药治疗有效率占60.91％;43例经验救治无效后使用补救方案治疗后,有效率达到93.02％,其中1例由于产生不良反应而停止使用,1例由于因感染性休克死亡.经验性用药为单一他唑巴坦/哌拉西林(27.27％)、伊曲康唑(10.00％),而联合用药主要为伊曲康唑+头孢他啶(17.27％),其次为伊曲康唑+万古霉素(9.09％);在经验治疗无效后,使用抗菌药物频率最高的为单一使用氟康唑(23.26％),其次为哌拉西林/他唑巴坦(16.28％),联合用药频率最高的为氟康唑+万古霉素(9.30％),其次为哌拉西林/他唑巴坦+万古霉素(6.98％).结论 该院抗菌药物使用情况合理,针对白血病化疗后粒细胞缺乏伴真菌感染患者应根据患者感染情况,合理选择抗菌药物.     

An Observational Study on the Epidemiology of Respiratory Tract Bacterial Pathogens and Their Susceptibility to Four Injectable Beta-Lactam Antibiotics: Piperacillin,Piperacillin/Tazobactam,Ceftazidime and Ceftriaxone

Abstract

Bacterial infections of the respiratory tract account for a large proportion of total medical consultations in general practice. In recent years, antibiotic resistance has increased alarmingly in a number of bacterial species that are common causes of these infections. The aim of this observational study was to determine the antibiotic resistance of microbial agents isolated from patients with acute or acutely exacerbated respiratory infections. Subjects recruited as potential sources of bacteria were either outpatients seen in a number of specialized clinics and hospital practices, or hospitalized patients. Overall, 64-a8 consecutive patients (67% male, mean age 48.1 ± 27.0 years) with infection of the upper or lower respiratory tract were observed during a 13-month period. A total of 551 pathogenic microbial strains were isolated and tested for their in vitro susceptibility to piperacillin, piperacillin/tazobactam, ceftazidime, and ceftriaxone. Among all isolates, the four most frequent pathogens were Pseudomonas aeruginosa (132 isolates, 24%), Streptococcus pyogenes (99 isolates, 18%), Staphylococcus aureus (93 isolates, 17%), and Klebsiella pneumoniae (46 isolates, 8%). The susceptibility of Gram-positive isolates ranged from 97.5% to 95.1%, and no remarkable difference was found in the antibacterial activity of tested b-lactam antibiotics. The susceptibility of Gram-negative isolates to piperacillin and piperacillin/tazobactam was also similar: 96.5% and 97.1%, respectively. In contrast, differences were found between piperacillin (or piperacillin/tazobactam) and either ceftazidime (p=0.003) or ceftriaxone (p<0.0003) in Gram-negative isolates.

We conclude that, despite the extensive use of beta-lactam antibiotics (piperacillin, ceftazidime, and ceftriaxone) in medical practice during the past three decades, the susceptibility of the most common pathogens involved in the etiology of upper and lower respiratory tract infections to these antibiotics is still high. In particular, bacterial resistance developed by Gram-positive organisms against piperacillin is negligible and not alarming.     

Resistance patterns of Pseudomonas aeruginosa to carbapenems and piperacillin/tazobactam.

Pseudomonas aeruginosa is a major problem as a multiresistant nosocomial pathogen, especially in burns and other immunocompromised patients in our hospital. The present prospective study, conducted between June 1996 and December 1997, was aimed at determining the extent of its resistance against highly active antipseudomonal drugs, such as carbapenems (imipenem and meropenem) and ureidopenicillin with beta-lactamase inhibitor (piperacillin/tazobactam); existence of any cross resistance or difference in susceptibility between imipenem and meropenem; and to compare the activity of piperacillin/tazobactam with the two carbapenems against P. aeruginosa. Of the 357 P. aeruginosa isolates tested from 188 patients 37 (10.4%) were resistant to imipenem, 21 (5.9%) to meropenem and 50 (14%) to piperacillin/tazobactam. Cross resistance between the two carbapenems was observed in 5.9% of the isolates. Sixteen (43%) of the imipenem-resistant isolates were susceptible to meropenem but the reverse was observed in none. Amongst the 50 piperacillin/tazobactam-resistant isolates cross resistance with the two carbapenems was observed in 18 (36%) and in 9 (18%) only with imipenem; 23 (46%) were susceptible to both. Our results indicate that P. aeruginosa is least resistant to meropenem followed by imipenem and piperacillin/tazobactam. Cross resistance between the carbapenems and between carbapenems and piperacillin/tazobactam was found. The study further suggests that burns, cardiac-neuro-pediatric surgical, cancer and transplant patients are more susceptible to acquiring infection due to multiresistant P. aeruginosa than other types of patients and common infection sites were wounds, respiratory tract, urine, blood and intravascular lines.     

P16INK4a Overexpression is Associated with Poor Clinical Outcome in Ovarian Carcinoma

Abstract

Tigecycline is the first Food and Drug Administration (FDA) approved glycylcycline antibiotic. It has shown remarkable in vitro activity against a wide variety of Gram-positive, Gram-negative and anaerobic bacteria including many multidrug resistant (MDR) strains. However, it has minimal activity against Pseudomonas aeruginosa and Proteus spp. To date, little resistance to tigecycline has been reported. Clinical trials studying complicated skin and skin-structure infections (cSSSIs) demonstrated that tigecycline has equivalent efficacy and safety compared with the combination of van-comycin and aztreonam. For complicated intra-abdominal infections (cIAIs), tigecycline was found to be as effective as imipenem/cilastatin. Adverse events related to tigecycline therapy, i.e. nausea and vomiting, were tolerable. Currently available data suggest that tigecycline may play an important role in the future as a monotherapy alternative to older broad-spectrum antibiotics, such as advanced generation cephalosporins, carbapenems, fluoroquinolones, piperacillin/tazobactam, and Gram-positive directed agents (e.g. daptomycin, linezolid and quinupristin/dalfopristin) for which resistance is being increasingly reported from all parts of the world.     

Piperacillin/tazobactam plus gentamicin as empirical therapy for febrile neutropenic patients with haematological malignancy.

The efficacy of piperacillin/tazobactam (PIPC/TBT) in combination with gentamicin was assessed as empirical therapy in 44 febrile neutropenic patients with haematological malignancy. A favourable response to therapy was seen in 67% patients overall and in 57% of patients with microbiologically documented infection. PIPC/TBT demonstrated good clinical and in vitro activity against isolated pathogens, particularly Gram positive cocci such as Staphylococcus epidermidis. The MIC of both Gram positive and Gram negative pathogens to PIPC was reduced in the presence of TBT. PIPC/TBT plus gentamicin is a safe and effective combination for empirical therapy in febrile neutropenic patients, even in a unit with a predominance of Gram positive infections.     

Resistance surveillance in Italy: four-year results from the MYSTIC program

The MYSTIC program is an international, multicenter surveillance study that compares the activity of meropenem, in centers that are prescribers, with that of imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin and gentamicin. These Italian data are from 3 centers (neutropenia, cystic fibrosis and intensive care units). A total of 2,072 (238 Gram-positive and 1,834 Gram-negative) aerobic microorganisms were collected during the study. Pseudomonas aeruginosa (33.4%) was the most isolated species followed by Escherichia coli (14.4%). All except one Enterobacteriaceae strain isolated were fully susceptible to meropenem. Moreover, the activity of meropenem against Enterobacteriaceae was about eight-fold greater than that of imipenem and four- to eight-fold more active than that of ceftazidime. Meropenem was highly active against non-fermentative Gram-negative microorganisms, exceeding the activity of most of the other antimicrobial agents tested. Moreover, meropenem showed increasing activity during the 4 years of study (starting from 86.2% in 1997 to 94.0% in 2000). In conclusion, our results indicate that meropenem has excellent potency and spectrum of activity despite being prescribed for the treatment of seriously ill patients, and appears to be a reliable option for the initial empirical treatment of serious nosocomial infections.     

Antimicrobial Resistance in Gram-Negative Hospital Isolates: Results of the Turkish HITIT-2 Surveillance Study of 2007

Abstract

Resistance rates to amikacin, ciprofloxacin, ceftazidime, cefepime, imipenem, cefoperazone/sulbactam and piperacillin/tazobactam in Escherichia coli (n= 438)Klebsiella pneumoniae (n= 444)Pseudomonas aeruginosa (n= 210) and Acinetobacterbaumanni (n=200) were determined with e-test in a multicenter surveillance study (HITIT-2) in 2007. ESBL production in Escherichia coli and K. pneumoniae was investigated following the CLSI guidelines. Overall 42.0% of E.coli and 41.4% of K. pneumoniae were ESBL producers. In E. coli, resistance to imipenem was not observed, resistance to ciprofloxacin and amikacin was 58.0% and 5.5% respectively. In K. pneumoniae resistance to imipenem, ciprofloxacin and amikacin was 3.1%, 17.8% 12.4% respectively. In P. aeruginosa the lowest rate of resistance was observed with piperacillin/tazobactam (18.1%). A. baumanni isolates were highly resistant to all the antimicrobial agents, the lowest level of resistance was observed against cefoperazone/sulbactam (52.0%) followed by imipenem (55.5%). This study showed that resistance rates to antimicrobials are high in nosocomial isolates and show variations among the centers.     

Bacteremia due to Pseudomonas aeruginosa: results from a 3-year national study in the Slovak Republic

Risk factors, mortality and antimicrobial susceptibility of Pseudomonas aeruginosa bacteremias isolated from 148 patients from all University Hospitals in Slovakia were analyzed. Only 1.2% of 169 strains of P. aeruginosa were resistant to meropenem, 4.1% to piperacillin/tazobactam, 7.7% to ceftazidime as well as cefepime and 12% to amikacin. More than 30% of P. aeruginosa were resistant to ciprofloxacin. Our analysis of risk factors for antimicrobial resistance to the particular antimicrobials, indicated no difference in risk factors and outcome in cases infected with P. aeruginosa bacteremias resistant to amikacin, piperacillin/tazobactam or ceftazidime in comparison to episodes caused by P. aeruginosa due to susceptible isolates. When comparing risk factors for P. aeruginosa bacteremia in children vs. adults, cancer vs. non-cancer patients, several differences in risk factors were observed. Neither antimicrobial resistance to amikacin, ceftazidime or piperacillin/tazobactam, nor appropriateness of therapy according to two separate analyses were associated with better outcome.     

Antimicrobial use and resistance among Gram-negative bacilli in an Italian intensive care unit (ICU)

Gram-negative bacilli antimicrobial resistance remains a significant problem for patients in the intensive care unit (ICU). We performed a retrospective analysis of microbiological data and antibiotic consumption over a 4-year period (2000-2003) in an Italian ICU. Pseudomonas aeruginosa and Klebsiella pneumoniae represented approximately 40% of all isolates. The most significant trend in antimicrobial use was an increase in use of 3(rd )generation cephalosporins, imipenem, and ciprofloxacin. A significant trend toward an increase in resistance rates to piperacillin, 3( rd )generation cephalosporins and ciprofloxacin was observed for K. pneumoniae and a positive correlation between resistance and drug-usage was evident for K. pneumoniae and piperacillin, cefotaxime, ceftazidime, cefepime, and ciprofloxacin, but not for piperacillin/tazobactam. No statistically significant correlations were evidenced for P. aeruginosa. Trends in resistances were studied also for Serratia spp and Proteus spp. Isolation rates of extended-spectrum beta-lactamase (ESBL)-producing strains in pathogens studied were high, especially for K. pneumoniae (72%, 160/222) and Proteus spp (41%, 18/43). In conclusion, the study showed high resistance among Gram-negative organisms isolated in the ICU and significant ESBL production. A significant correlation between antibiotic consumption and increasing resistance was evident for K. pneumoniae.     

Aztreonam plus vancomycin versus gentamicin plus piperacillin as empirical therapy for the treatment of fever in neutropenic patients: a randomised controlled study.

The efficacy of aztreonam in combination with vancomycin was compared with that of gentamicin plus piperacillin as empirical antibiotic treatment for fever in 61 neutropenic patients. Aztreonam plus vancomycin was as effective, but no more effective, than gentamicin plus piperacillin. Aztreonam showed excellent clinical and in vitro efficacy against Gram-negative pathogens. Failure to respond to aztreonam plus vancomycin was, in most cases, due to presumed or documented fungal infection; by contrast, failure to respond to gentamicin plus piperacillin was frequently to be due to resistant or superadded infection with Gram-positive bacteria.     

Bacterial susceptibilities to piperacillin/tazobactam in a tertiary care hospital: 5-year review

Several factors influence the speed of development of antibacterial resistance, among which is the amount of antibiotic consumption. During the 3-year period 1998-2000, the consumption of piperacillin/tazobactam (pip/tazo) increased by 85% in our hospital. Five years ago we conducted a comparative in vitro study to evaluate susceptibilities of microorganisms to pip/tazo. The objective of the present study was to re-evaluate in vitro susceptibilities to pip/tazo, compared to other beta-lactams, and the potential impact its increased consumption might have on its susceptibility patterns. The study was performed between November 2000 and April 2001. As in 1996, of the beta-lactams studied, pip/tazo and imipenem had the highest susceptibility rates against selected pathogens (>90% susceptibility rates). P. aeruginosa susceptibilities to both imipenem and pip/tazo were high (97% for both). P. aeruginosa susceptibilities to cefepime were lower. Despite its increased use, pip/tazo retained its initially observed high susceptibility rates for the study pathogens.     

Resistance Surveillance in Italy: Four-Year Results from the MYSTIC Program

Abstract

The MYSTIC program is an international, multicenter surveillance study that compares the activity of meropenem, in centers that are prescribers, with that of imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin and gentamicin. These Italian data are from 3 centers (neutropenia, cystic fibrosis and intensive care units). A total of 2,072 (238 Gram-positive and 1,834 Gramnegative) aerobic microorganisms were collected during the study. Pseudomonas aeruginosa (33.4%) was the most isolated species followed by Escherichia coli (14.4%). All except one Enterobacteriaceae strain isolated were fully susceptible to meropenem. Moreover, the activity of meropenem against Enterobacteriaceae was about eight-fold greater than that of imipenem and four- to eight-fold more active than that of ceftazidime. Meropenem was highly active against non-fermentative Gram-negative microorganisms, exceeding the activity of most of the other antimicrobial agents tested. Moreover, meropenem showed increasing activity during the 4 years of study (starting from 86.2% in 1997 to 94.0% in 2000). In conclusion, our results indicate that meropenem has excellent potency and spectrum of activity despite being prescribed for the treatment of seriously ill patients, and appears to be a reliable option for the initial empirical treatment of serious nosocomial infections.     

Aztreonam plus Vancomycin versus Gentamicin plus Piperacillin as Empirical Therapy for the Treatment of Fever in Neutropenic Patients: a Randomised Controlled Study

The efficacy of aztreonam in combination with vancomycin was compared with that of gentamicin plus piperacillin as empirical antibiotic treatment for fever in 61 neutropenic patients. Aztreonam plus vancomycin was as effective, but no more effective, than gentamicin plus piperacillin. Aztreonam showed excellent clinical and in vitro efficacy against Gram-negative pathogens. Failure to respond to aztreonam plus vancomycin was, in most cases, due to presumed or documented fungal infection; by contrast, failure to respond to gentamicin plus piperacillin was frequently to be due to resistant or superadded infection with Gram-positive bacteria.     

Piperacillin/Tazobactam Plus Gentamicin as Empirical Therapy for Febrile Neutropenic Patients with Haematological Malignancy

Summary

The efficacy of piperacillin/tazobactam (PIPC/TBT) in combination with gentamicin was assessed as empirical therapy in 44 febrile neutropenic patients with haematological malignancy. A favourable response to therapy was seen in 67% patients overall and in 57% of patients with microbiologically documented infection. PIPC/TBT demonstrated good clinical and in vitro activity against isolated pathogens, particularly Gram positive cocci such as Staphylococcus epidermidis. The MIC of both Gram positive and Gram negative pathogens to PIPC was reduced in the presence of TBT. PIPC/TBT plus gentamicin is a safe and effective combination for empirical therapy in febrile neutropenic patients, even in a unit with a predominance of Gram positive infections.