Piperacillin is an aminobenzyl-penicillin derivative with the chemical formula sodium 6-(D(–)-a-(4-ethyl-2,3-dioxo-1-piperazinyl carbonylamino a-phenylacetamido) penicillinate. Its molecule contains a side chain with an ureido group, but because of chemical differences arising from its terminal piperazine structure, it is often not classified as a ureidopenicillin like mezlocillin and azlocillin.  Piperacillin has an in vitro antimicrobial spectrum qualitatively, but not quantitatively, similar to that of carbenicillin [1-2]. Piperacillin alone is available, but its use has recently declined somewhat. Instead, it is now mainly used in the fixed combination of piperacillin and tazobactam, a b-lactamase inhibitor.

Therapeutic use

Piperacillin can be used either alone or in a fixed combination with the b-lactamase inhibitor tazobactam. Similar to mezlocillin, piperacillin can be used to treat severe infections caused by sensitive Gram-negative aerobic and anaerobic bacteria with the benefit of avoiding the toxicity of aminoglycoside therapy [3-5].

Intra-abdominal and pelvic infections (treatment and surgical prophylaxis)

Piperacillin monotherapy has been used successfully to treat complicated intra-abdominal infections including perforated appendicitis, generalized peritonitis, and intra-abdominal abscesses with success rates of 83–91% [5-9]. It is important to note that there were low rates of piperacillin resistance in these studies and most patients had surgery and/or drainage of abscesses. In a study of patients with penetrating abdominal trauma, piperacillin monotherapy was equally efficacious as combination therapy with gentamicin and metronidazole, with a cure achieved in 94% of patients [10]. Piperacillin monotherapy was also used in a randomized trial examining delayed laparoscopic cholecystectomy for acute cholecystitis with a 68.2% response [11]. It has been used for the treatment of acute cholangitis, but with the high prevalence of resistant amongst E. coli and Klebsiella spp., combination with tazobactam is now the preferred treatment option [12-13].

In a randomized controlled trial, piperacillin demonstrated excellent efficacy (94% vs 71% for placebo) as prophylaxis against cholangitis in
patients undergoing endoscopic retrograde cholangiopancreatography [14]. In an uncontrolled trial, the drug was found satisfactory for chemoprophylaxis in patients undergoing elective biliary surgery [15]. However, high rates of piperacillin resistance (up to 58%) have been reported among Aeromonas spp. isolated from biliary specimens [16]. These resistant Aeromonas spp. were isolated from patients who had multiple biliary procedures. Piperacillin has also been shown to be effective as prophylaxis for cesarean section and gynecologic surgery [17-18]. Efficacy was equivalent to that of cefotetan. Although effective as monotherapy in the prevention of infection in colorectal
surgery, superior regimens include piperacillin–tazobactam, piperacillin–aminoglycoside–metronidazole, cefuroxime–metronidazole, and cefoxitin [19-22]. In addition to these findings, antimicrobial resistance and toxicity of aminoglycosides means that except for the combination of piperacillin–tazobactam, piperacillin-based regimens are unlikely to be recommended as preferred options for treatment or prophylaxis of serious intra-abdominal and pelvic infections.

Empiric treatment of febrile neutropenia

Piperacillin has been studied in combination with  b-lactamase inhibitors, aminoglycosides, ciprofloxacin, and cephalosporins for empiric treatment of febrile neutropenia. In one small trial (50 infections) comparing piperacillin as monotherapy with carboxypenicillin–aminoglycoside as empiric treatment of serious bacterial infections, 30 patients with fever and neutropenia were included [23]. This study demonstrated that emergence of resistant organisms was more common during piperacillin therapy, which resulted in treatment failures and superinfections. Several studies have demonstrated efficacy of piperacillin–aminoglycoside combinations. A piperacillin–amikacin combination was shown to be equally as effective as a carbenicillin or ticarcillin–amikacin combination in febrile neutropenic patients [24-26]. More recently, a meta-analysis of beta-lactam monotherapy versus beta-lactam–aminoglycoside combination for the treatment of febrile neutropenia found that there was greater success and less toxicity, particularly nephrotoxicity, with monotherapy regimens not including piperacillin [27]. Ceftazidime monotherapy was shown in a large trial of 876 febrile neutropenic episodes to be superior to piperacillin–tobramycin in the clearance of Gram-negative bacteremia [28]. Another large trial of 470 episodes of febrile neutropenia demonstrated superiority of ceftazidime–vancomycin compared with piperacillin–vancomycin with greater success for all febrile episodes, as well as those with microbiologically confirmed infections, including bacteremia [29]. Three trials comparing a piperacillin–aminoglycoside combination with cefepime montherapy have shown equally efficacy [30-32]. In two individual trials, imipenem demonstrated a ‘‘trend’’ toward increased efficacy and clearance of infections with less nephrotoxicity and ototoxicity than piperacillin–aminoglycoside [33-34]. A trial comparing the combination of cefotaxime with piperacillin with imipenem suggested imipenem to be superior to the piperacillin combination in patients who had primary bacteremia [35]. Three trials have compared the combination of piperacillin–aminoglycoside with ciprofloxacin–piperacillin [36-37] or ciprofloxacin–penicillin G [38]. Greater efficacy with less toxicity was seen with ciprofloxacin–betalactam

Bacteremia, lower respiratory tract infections, and other Gram-negative infections

Piperacillin is useful for the treatment of P. aeruginosa infections [39], but despite its superior in vitro activity, it has not been shown to be clinically superior to carbenicillin, ticarcillin, or ticarcillin–aminoglycoside combinations [40-41]. Combination therapy with an aminoglycoside does not appear to prevent P. aeruginosa developing resistance [42]. Treatment of P. aeruginosa endocarditis with piperacillin–tobramycin has been associated with failure and in vivo development of piperacillin reistance [43]. Listeria monocytogenes bacteremia has also been successfully treated with piperacillin–amikacin [44.]. Piperacillin is highly effective in the treatment of pneumonia caused by S. pneumoniae, H. influenzae, Enterobacteriacae, Pseudomonas spp., and anaerobes [41, 45-48]. However, piperacillin usefulness in the empiric treatment of community-acquired pneumonia may be limited due to the level of resistance amongst penicillin-resistant S. pneumoniae [49-50]. It has been used successfully as monotherapy in the treatment of lower respiratory tract infections due to sensitive P. aeruginosa and Enterobacteriaciae [4-5, 51]. In a murine model of K. pneumoniae pneumonia, piperacillin monotherapy led to regrowth of bacterial counts after an initial significant decrease [52]. In this study combination with tazobactam had similar efficacy to cefotaxime, which achieved a sustained decrease in bacterial counts. Piperacillin has also been used with some success to treat acute exacerbations of pulmonary disease in patients with cystic fibrosis [53]. In one small study involving cystic fibrosis patients, no clinical benefit or reduction in sputum P. aeruginosa counts was seen with the addition of piperacillin to tobramycin–flucloxacillin [54]. However, others have shown that it remains an effective option for the treatment of infective exacerbations of cystic fibrosis with susceptible P. aeruginosa and B. cepacia infections [55-56].


Piperacillin monotherapy has been used successfully to treat meningitis in neonates and adults due to S. pneumoniae, Chryseobacterium (Flavobacterium) meningosepticum, and Achromobacter (Alcaligenes) xylosoxidans [57-61]. As monotherapy and in combination with colistin, piperacillin has been successful in the treatment of meningitis due to P. aeruginosa, although failures have been reported with piperacillin montherapy [57, 62].

Dosage and Administration

Both i.m. and i.v. administrations are suitable, but the i.v. route is preferable when large doses are used. The usual dosage is 200–300 mg/kg body weight per day, given in six divided doses [3,63]. A low adult dosage suitable for milder infections is 4–12 g daily, given in four divided doses; for more serious infections this may be increased to 12–24 g daily, administered in six divided doses [64]. Each i.v. dose is usually infused over 15–30 minutes.

Continuous infusion of 8 g i.v. daily following a 2-g i.v. loading dose given over 0.5 hours has been studied in critically ill patients achieving mean serum concentrations of piperacillin of 36, 34, 42, and 34 mg/ml at 6, 12, 24, and 48 hours [65]. A Monte Carlo simulation predicted that a 4-hour infusion of 3 g i.v. every 8 hours was more likely to achieve 50% time above MIC for MIC values between 8 and 16   mg/ml than a 0.5-hour infusion of 3 g every 4 hours [66].


In children, an i.v. dose of 50 mg/kg body weight, administered every 4 hours, is recommended [67]. In neonates, 75 mg/kg i.v. every 12 hours during the first week of life and every 8 hours in the second week provides appropriate concentrations in those of less than 36 weeks gestational age. In full-term newborns, 75 mg/kg i.v. every 8 hours is appropriate during the first week of life, and the same dose four times daily should be given thereafter [68].

Impaired renal function

In patients with mild renal failure, the usual piperacillin dosage can probably be used, but in moderate renal failure (creatinine clearance 0–40 ml/min) dosage should not exceed 12 g daily (4 g 8-hourly). In patients with severe renal failure (creatinine clearance <20 ml/min), dosage should be reduced to 4 g 12-hourly. Some piperacillin is removed by hemodialysis, so that a 2–4 g i.v. piperacillin dose can be given after each hemodialysis, with a regimen of 4 g 12-hourly being used between dialyses [69-70]. Other authors recommend only approximately half of the above dosages for patients with both moderate and severe renal failure [71]. In patients with combined severe renal and hepatic insufficiency, a further reduction of piperacillin dosage is necessary [72]. In patients on peritoneal dialysis who develop peritonitis, the recommended piperacillin dose is 2 g i.v. every 8 hours or 1 g every 6 hours in the dialysate [73]. Continuous venovenous hemofiltration does not remove piperacillin [74].

Impaired hepatic function

Dosage reduction is necessary for patients who have hepatic insufficiency in association with severe renal impairment [72].

Cystic fibrosis

Patients with cystic fibrosis require higher doses to achieve serum levels similar to those attained in normal patients of similar age; a dosage of 500–600 mg/kg/day, almost twice the normal dosage, is required [53, 75]. This difference in dose requirement is no longer seen after correction for lean body mass [66]. Using Monte Carlo simulation, a dose of 3 g/70 kg body weight was more than 90% likely to achieve time above MIC of greater than 50% for MIC 12 mg/ml. A 4-hour infusion of 3 g every 8 hours or 9 g daily continuous infusion was
predicted to achieve this same probability of target attainment for MIC16 mg/ml.


Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
dog LD50 intravenous > 6gm/kg (6000mg/kg)   Japanese Journal of Antibiotics. Vol. 36, Pg. 653, 1983.
monkey LD50 intravenous > 4gm/kg (4000mg/kg)   Drugs in Japan Vol. 6, Pg. 634, 1982.
mouse LD50 intraperitoneal 9770mg/kg (9770mg/kg) LUNGS, THORAX, OR RESPIRATION: RESPIRATORY STIMULATION


Chemotherapy Vol. 25, Pg. 816, 1977.
mouse LD50 intravenous 4900mg/kg (4900mg/kg) LUNGS, THORAX, OR RESPIRATION: RESPIRATORY STIMULATION


Chemotherapy Vol. 25, Pg. 816, 1977.
mouse LD50 oral > 10gm/kg (10000mg/kg)   Drugs in Japan Vol. 6, Pg. 634, 1982.
mouse LD50 subcutaneous > 10gm/kg (10000mg/kg)   Drugs in Japan Vol. 6, Pg. 634, 1982.
rat LD50 intraperitoneal 7600mg/kg (7600mg/kg) LUNGS, THORAX, OR RESPIRATION: RESPIRATORY STIMULATION


Chemotherapy Vol. 25, Pg. 816, 1977.
rat LD50 intravenous 2260mg/kg (2260mg/kg)   Iyakuhin Kenkyu. Study of Medical Supplies. Vol. 10, Pg. 884, 1979.
rat LD50 oral > 10gm/kg (10000mg/kg)   Drugs in Japan Vol. 6, Pg. 634, 1982.
rat LD50 subcutaneous 8800mg/kg (8800mg/kg)   Iyakuhin Kenkyu. Study of Medical Supplies. Vol. 10, Pg. 884, 1979.
rat LD50 unreported 2gm/kg (2000mg/kg)   United States Patent Document. Vol. #4535078,
women TDLo intramuscular 960mg/kg/3D-I (960mg/kg) BLOOD: HEMORRHAGE Southern Medical Journal. Vol. 78, Pg. 363, 1985.
women TDLo intravenous 2180mg/kg/6D- (2180mg/kg) BLOOD: LEUKOPENIA

Southern Medical Journal. Vol. 79, Pg. 255, 1986.

Hypersensitivity reactions

In a survey of 485 hospitalized patients treated with piperacillin, the frequency of hypersensitivity reactions, such as drug fever, rashes, pruritus, and eosinophilia, was approximately 4% [76]. A case of occupational asthma, rhinitis, and urticaria due to piperacillin has been reported in a pharmaceutical worker [77].


High doses of piperacillin given i.v., similar to ‘‘massive’’ doses of penicillin G or carbenicillin, may have the propensity to cause neurotoxicity [78].

Bleeding disorders

Similar to carbenicillin and ticarcillin, mezlocillin, azlocillin, piperacillin, and apalcillin can cause a disturbance of platelet function [79-80]. Mezlocillin, piperacillin, and apalcillin have a lesser effect on platelet function than carbenicillin and ticarcillin at an equivalent dosage [80-83].

Neutropenia and thrombocytopenia

As with carbenicillin and ticarcillin and other b-lactam antibiotics, reversible neutropenia can occur during therapy with mezlocillin, azlocillin, and piperacillin [76, 84-85]. This side-effect is more common with these penicillins than with carbenicillin. Thrombocytopenia can also rarely occur [86-88]. Piperacillin-induced neutropenia has been reviewed [89].


Elevations of hepatic enzymes and slight elevations of the serum bilirubin occurred in 3% of patients treated with piperacillin; one patient developed cholestatic hepatitis which reappeared with increased severity upon rechallenge with the drug [76].

Other side-effects

Some patients have developed nausea and diarrhea associated with parenteral use of this drug. A positive Coombs’ test has developed in a few patients treated by either mezlocillin or piperacillin, but hemolytic anemia has not been observed. In animals, piperacillin appears to protect against gentamicin induced nephrotoxicity [90]. Similarly, the drug protects against cisplatin induced renal damage in rats [91].


The pharmacokinetic of piperacillin is dose dependent [92-93], with half-lives varying between 40 minutes and 1.3 hours. The mean protein binding is 16% at concentrations in the range 200–300 mg/ml [92].

Bioavailability 0%
Protein binding 16%
Metabolism Largely not metabolized.
Half-life 36-72 minutes
Cmax (mg/ml)  
tmax (hrs)  
Distribution volume Vd 101 mL/kg [intravenous administration of 50 mg/kg (5-minute infusion) in neonates]
Clearance 32 - 41 mL/min/1.73 m2
124 - 160 mL/min/1.73 m2 [older pediatric patients]
Excretion renal


The drug is not orally available.


Following administration of single i.m. doses of piperacillin 0.5, 1, and 2 g to healthy adults, mean peak serum levels of 4.9, 13.3, and 30.2 mg/ml, respectively, occur at 30–50 minutes; measurable levels after these three doses are present up to 4, 6, and 8 hours, respectively, after dosing. Immediately after rapid (bolus) i.v. injections of 1, 2, 4, or 6 g of piperacillin, serum levels were 70.7, 199.5, 330.7, and 451.8 mg/ml, respectively. After a 5-minute i.v. infusion of 4 g of piperacillin, peak plasma levels in healthy volunteers and cystic fibrosis patients were 446 and 767 mg/ml, respectively [66]. If piperacillin is administered i.v. more slowly, as a 30-minute or 2-hour infusion, peak serum levels after the infusions are lower than after rapid i.v. injections, but the areas under the curve for each method of administration are the same with comparable doses. All of these methods of i.v. administration of piperacillin appear satisfactory clinically [94-95].

Piperacillin penetrated poorly into bronchial secretions, where concentrations of only 1–5 mg/ml were attained with usual doses [4]. Mezlocillin, azlocillin, and piperacillin penetrated well into interstitial and wound fluids, but after usual doses only low levels were reached in normal bone [92].

Twenty-eight adult patients undergoing open heart surgery were given 4 g piperacillin i.v. preoperatively, which resulted in a serum level of 173.8 mg/ml, which declined to 14.4 mg/ml in 6 hours. Mean concentrations in cardiac valvular tissue were 48 mg/g at 0.5–1.0 hours, and 11.8 mg/g 4–5 hours after piperacillin administration; mean subcutaneous and muscle concentrations varied from 11.8 to 7.1 mg/g during this time [96].

For piperacillin, data indicate that its penetration into prostatic tissue and prostatic fluid is relatively low and variable following a single 1-g i.v. dose [97].   The penetration of piperacillin into the vitreous cavity following a single i.v. dose of 4 g given 2 hours prior to ocular incision [98]. Mean concentrations were 0.4 mg/ml in uninflamed eyes and 5.0 mg/ml in inflamed eyes, which represented higher concentrations than the MICs of isolated bacteria in 13% and 69%, respectively.

Provided the biliary tract is not obstructed, high biliary concentrations are attained with these agents. Piperacillin biliary concentrations in the common duct were in the range 31–920 mg/ml, 35–90 minutes after an i.v. dose of 1 g, in postoperative patients after cholecystectomy
[99]. After i.v. administration of a 5-g dose of piperacillin to patients undergoing biliary tract surgery, peak levels in bile exceeded 4000 mg/ml, but, in one patient with cystic duct obstruction, levels in the gall bladder bile were subtherapeutic [100]. In one study, biliary excretion of piperacillin was assessed in 11 patients with obstructive jaundice due to cholangiocarcinoma. After a 1-g i.v. dose, no drug was detected in bile in the majority of patients. In the others, bile levels were much lower than serum levels. After a period of external biliary drainage of up to 28 days, levels of antibiotic in bile after i.v. administration were only minimally increased, although liver function was improved as judged by fall in serum bilirubin [101].

In animals, piperacillin penetrates poorly into normal cerebrospinal fluid (CSF). Piperacillin was used to treat four patients with bacterial meningitis (three P. aeruginosa, one Flavobacterium meningosepticum) in a dosage ranging from 324 to 436 mg/kg body weight per day given by continuous i.v. infusion. This resulted in a mean CSF level of 23 mg/ml 24 hours after starting therapy, which was 32% of the mean serum level at the time [57].

In pregnant women who received a single piperacillin dose of 4 g, the mean Cmax was 8 mg/ml compared with 172 mg/ml in nonpregnant controls. The fetomaternal ratio at the time of cesarean section was 0.27 [102].


Mezlocillin, azlocillin, and piperacillin are excreted unchanged in the urine by both glomerular filtration and tubular secretion. Approximately
50–80% of an i.v. dose of these drugs is eliminated via the kidneys in an unchanged form [103-105]. With dose increments, an increasing proportion of all these drugs is recovered unchanged in the urine. This is because with higher doses nonrenal mechanisms for drug elimination become saturated. Probenecid decreases renal excretion of these penicillins by partial blockage of renal tubular secretion. High concentrations of the active form of all these drugs are attained in the urine after usual i.m. or i.v. doses.

Significant amounts of mezlocillin, azlocillin, piperacillin, and apalcillin are eliminated via the bile. The percentage of these drugs eliminated via bile may increase in patients with impaired hepatic function; this is probably because there is less biotransformation in the liver [92].




Mechanism of Action

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, Piperacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that Piperacillin interferes with an autolysin inhibitor.

Antibacterial activity

The antibacterial spectra of ureidopenicillins are similar to those of carbenicillin and ticarcillin, but there are differences between their degree of activity against various bacterial species. All of these antibiotics have lost much of their activity owing to emergence of resistance. To some extent, that problem has been reduced for mezlocillin and piperacillin, which are available in fixed combinations with sulbactam and tazobactam, respectively. The comparative in vitro susceptibility data for these agents against common pathogens are shown in Table 1.

Table 1. In vitro susceptibility of common pathogens to mezlocillin, azlocillin, piperacillin, and apalcillin in comparison with ticarcillin.


MIC (mg/ml)

Ticarcillin Mezlocillin Azlocillin Piperacillin Apalcillin
Staphylococcus aureus, non penicillinase producer 1.25 0.2 0.2 0.78 0.39
Staphylococcus pyogenes 0.5 0.025 <0.1 0.1 0.1
Streptococcus pneumoniae 1.25 0.025 0.1 0.01 0.05
Enterococcus faecalis 125 1 0.5 0.4-1.6 12.5
Clostridium perfringens 0.5 0.07 0.04 0.06-4 1.56
Escherichia coli 5 1-2 1-8 0.8 0.39
Enterobacter spp. 5 2-8 12.5-100 1.6 3.1
Klebsiella spp. 500 12.5-100 12.5->100 3.1 6.3
Serratia marcescens 12.5 12.5 12.5 0.8->100 25
Proteus mirabilis 1.25 1.56 1.56 0.2 0.76
Proteus vulgaris 2.5 1.56 12.5 0.78 12.5
Morganella morganii 2.5 1.56 12.5 0.78 3.1
Salmonella typhi 2.5 2 8 0.39 3.1
Neisseria gonorrheae 0.02 0.005 0.005 0.015-0.03 0.1
Haemophilus influenzae 0.25 0.15-0.25 0.06 0.015-0.03 -
Pseudomonas aeruginosa 25 25-50 12.5 6.5 6.3
Prevotella melaninogenica 0.1-4 0.5-4 - - -
Bacteroides fragilis 4-128 1-128 1-128 25 25

Gram-positive bacteria

This drug is at least equally as active and, in the case of many strains, twice as active as azlocillin and carbenicillin against P. aeruginosa (see Table 1) [106-107]. Other Pseudomonas species, such as Burkholderia cepacia, are more susceptible to piperacillin than to carbenicillin [108]. Piperacillin has good activity against the Enterobacteriaceae. Previously, most strains of E. coli, P. mirabilis, and Klebsiella, Enterobacter, Serratia, Citrobacter, Salmonella, and Shigella spp. were inhibited by low concentrations, with MICs being similar to or sometimes lower than those of mezlocillin (Table 1) [109]. Since 1997, resistance in Enterobacteriaceae has significantly increased to as high as 50% in some areas [110-114]. The major mechanism of resistance amongst Enterobacteriaceae is inactivation by b-lactamases. This has resulted in piperacillin being more active against Enterobacteriaceae than ampicillin and ticarcillin alone, but generally less active
than ticarcillin–clavulanate, ampicillin–sulbactam, and piperacillin–tazobactam [112]. Piperacillin has no activity against Enterobacteriaceae with chromosome-encoded inducible AmpC b-lactamases that are resistant to ceftazidime [49]. Only about 50% of P. vulgaris, Morganella morganii, and Providencia and Acinetobacter spp. strains were inhibited by low piperacillin concentrations [1, 115-116]. Aeromonas spp. are usually piperacillin sensitive, except Aeromonas jandaei, which is usually resistant [117-118]. High rates of resistance among other non-veronii Aeromonas spp. have been seen in biliary isolates from patients with cholangitis [16]. Most isolates of Achromobacter xylosoxidans are susceptible [119]. Chryseobacterium indologenes is usually susceptible to piperacillin, whereas around 60% of C. meningosepticum isolates are susceptible [120]. Although H. influenzae is very susceptible to piperacillin, b-lactamase-producing strains are resistant. The drug is inactivated by the TEM-type beta-lactamase [121]. It is as active as penicillin G and mezlocillin against penicillin
G-susceptible N. gonorrhoeae strains (Table 1). Piperacillin exhibits increased activity against gonococcal strains with intrinsic-type resistance to penicillin G [122]. b-lactamase producing gonococci are piperacillin resistant ([123]. Piperacillin is moderately active against B. fragilis, with most strains being inhibited by 25 mg/ml; in this respect, it is about equally as active as mezlocillin [124-125]. Piperacillin-resistant variants of this organism have been detected in up to 9% of isolates [126-128]. Metronidazole and clindamycin are more active than piperacillin against Bacteroides spp. [128]. The activity of piperacillin against other species of Gram-negative anaerobic bacteria is variable: some strains are quite sensitive, but many are highly resistant [129].

Gram-positive bacteria

The activity of piperacillin against Gram-positive bacteria is similar to that of mezlocillin and azlocillin (Table 1) [123, 130]. Piperacillin is highly active against penicillin susceptible Streptococcus spp. and non-b-lactamase producing strains of S. aureus, S. epidermidis, and Enterococcus faecalis [49, 123, 130-131]. Except for a small number of isolates that produce b-lactamases, Gram-positive anaerobes such as Clostridium spp. are usually sensitive to piperacillin [132]. This includes Clostridium difficile, which is susceptible [49, 133]. Chlamydia trachomatis is piperacillin resistant [134]. Activity against S. pneumoniae correlates with penicillin G activity, with mutations in PBP2b leading to reduced piperacillin affinity [49-50, 135] ]. Tazobactam does not improve the activity of piperacillin against penicillin G-resistant S. pneumoniae [136]. Penicillin G and ampicillin are more active than piperacillin against viridans group streptococci [131].

Resistance and cross-resistance

Similar to mezlocillin and azlocillin, piperacillin is susceptible to b-lactamases, so that many Gram-negative bacteria with acquired resistance to ampicillin or carbenicillin are also piperacillin resistant [116, 137-138]. Chromosomally encoded, inducible AmpC b-lactamases are reported to occur at significant rates in several clinically important Gram-negative bacteria including Enterobacter spp., Pseudomonas aeruginosa, Acinetobacter spp., Morganella morganii, Citrobacter spp., and S. marcescens [139]. Plasmid-encoded Amp C b-lactamases are an emerging threat that inactivates piperacillin in the presence of tazobactam. In one study, most isolates of E. coli and K. pneumoniae with a positive screen for ESBL (MIC >1 mg/ml for ceftriaxone, ceftazidime, or aztreonam) had either plasma-encoded ESBLs or Amp C b-lactamases [140]. With P. aeruginosa, intrinsic resistance to piperacillin due to changes in penicillin-binding proteins (PBPs), particularly PBP3, has emerged in vivo during piperacillin treatment of P. aeruginosa infections in cystic fibrosis patients [141]. In an in vitro study, piperacillin resistant variants were detected in each of ten strains of P. aeruginosa. This resistance was due to an increased production of chromosomally mediated P. aeruginosa b-lactamase; the resistant strains remained stable on subculture and they arose as a result of chromosomal mutation – enzyme induction was not involved [142]. P. aeruginosa isolates resistant to ceftazidime and aztreonam are associated with cross-resistance to piperacillin [143-144]. This cross-resistance has relevance for antibiotic stewardship programs in which a reduction in P. aeruginosa isolates resistant to piperacillin was associated with a formulary change of ceftazidime and ceftriaxone to cefepime [145]. In contrast, a study in intensive care units showed that acquisition of P. aeruginosa was negatively associated with aanti-pseudomonal cephalosporin use, but associated with piperacillin–tazobactam use [146]. Some investigators have shown that quinolone resistance among P. aeruginosa isolates is not associated with piperacillin cross-resistance [143, 147-148]. However, an association between piperacillin and levofloxacin resistance exists when quinolone-resistant isolates are examined for efflux overexpression [149]. This association of cross-resistance between quinolones and piperacillin via efflux overexpression has also been described in E. coli, in which efflux overexpression occurred in 51% of quinolone-resistant isolates [148].

In vitro synergy and antagonism

In combination with an aminoglycoside (such as gentamicin, tobramycin, amikacin, or netilmicin), ureidopenicillins act synergistically against many strains of Gram-negative bacilli, such as P. aeruginosa, E. coli, P. vulgaris, P. rettgeri, Morganella morganii, and Klebsiella, Citrobacter, Enterobacter, and Serratia spp.

Other pharmacological effects

 Similar to other beta-lactams, the clinical efficacy of these agents is likely to be related to the duration the serum concentrations are above the MIC of the infecting pathogen. In critically ill patients, a 2 g i.v. loading dose of piperacillin followed by continuous i.v. infusion of 8 g daily achieved percentage time above MIC of 100% and 65% for MICs of 16 and 32 mg/ml, respectively [65]. This was superior to intermittent infusion of 3 g i.v. every 6 hours, which achieved T>MIC of 62% and 39%, respectively. The continuous-infusion regimen was associated with a more rapid decline in APACHE II scores in the first 4 days.

With piperacillin, following a single i.v. dose of 4 g, significantly lower concentrations in interstitial muscle and subcutaneous adipose tissue were obtained in severely ill patients than in healthy volunteers [150]. Despite this, a better bactericidal effect was shown for ill patients when the concentrations ahieved were assessed in vitro against strains of P.aeruginosa [151]. The authors suggested that this effect was due to the fact that piperacillin levels were above MIC in patients for a longer time, probably because of impaired excretion related to impaired renal function.

Medicinal Chemistry

CAS number: 59703-84-3  EINECS: 261-868-6

Molecular Formula:  C23H27N5O7S

Average mass: 517.55481 Da

Monoisotopic mass:  517.163147 Da

Systematic name: (2S,5R,6R)-6-{[(2R)-2-{[(4-Ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino}-2-phenylacetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

SMILES: CCN1CCN(C(=O)C1=O)C(=O)N[C@H](C2=CC=CC=C2)C(=O)N[C@H]3[C@@H]4N(C3=O)[C@H](C(S4)(C)C)C(=O)O

Std. InChI: 1S/C23H27N5O7S/c1-4-26-10-11-27(19(32)18(26)31)22(35)25-13(12-8-6-5-7-9-12)16(29)24-14-17(30)28-15(21(33)34)23(2,3)36-20(14)28/h5-9,13-15,20H,4,10-11H2,1-3H3,(H,24,29)(H,25,35)(H,33,34)/t13-,14-,15+,20-/m1/s1

ACD/LogP: 1.88±0.37 # of Rule of 5 Violations: 2
ACD/LogD (pH 5.5): -1.10 ACD/LogD (pH 7.4): -1.85
ACD/BCF (pH 5.5): 1.00 ACD/BCF (pH 7.4): 1.00
ACD/KOC (pH 5.5): 1.00 ACD/KOC (pH 7.4): 1.00
#H bond acceptors: 12 #H bond donors: 3
#Freely Rotating Bonds: 6 Polar Surface Area: 181.73 Å2
Index of Refraction: 1.678 Molar Refractivity: 128.5±0.4 cm3
Molar Volume: 340.5±5.0 cm3 Polarizability: 50.9±0.5 10-24cm3
Surface Tension: 80.6±5.0 dyne/cm Density: 1.5±0.1 g/cm3
Flash Point: °C Enthalpy of Vaporization: kJ/mol
Boiling Point: °C at 760 mmHg Vapour Pressure: mmHg at 25°C


Major Impurities:


Melting point:

Optical rotation:


logP: 0.3




1. Fu K.P., Neu H.C. "Piperacillin, a new penicillin active against many bacteria resistant to other penicillins". Antimicrob. Agents Chemother. 13: 358, (1978).

2. Selwyn S. "The evolution of the broad-spectrum penicillins". J. Antimicrob. Chemother. Suppl. B 1, (1982).

3. Winston D.J., Murphy W., Young L.S., Hewitt W.L. "Piperacillin therapy for serious bacterial infections". Am. J. Med. 69: 255, (1980).

4. Pancoast S., Prince A.S., Francke E.L., Neu H.C. "Clinical evaluation of piperacillin therapy for infection". Arch. Intern. Med. 141: 1447, (1981).

5. Gooding P.G., Clark B.J., Sathe S.S." Piperacillin: a review of clinical experience". J. Antimicrob. Chemother. 9 Suppl.: 93, (1982).

6. Najem A.Z., Kaminski Z.C., Spillert C.R., Lazaro E.J. "Comparative study of parenteral piperacillin and cefoxitin in the treatment of surgical infections of the abdomen. Surg. Gynecol. Obstet. 157: 423, (1983).

7. Vergnaud M., Ravasse P., Eustratiades N. et al. "[Effectiveness of piperacillin in the antibacterial treatment of intra-abdominal infections in children]". Presse Med. 15: 2342, (1986).

8. Scheinin H., Havia T., Pekkala E. et al. "Aspoxicillin versus piperacillin in severe abdominal infections – a comparative phase III study". J. Antimicrob. Chemother. 34: 813, (1994).

9. Ciftci A.O., Tanyel F.C., Buyukpamukcu N., Hicsonmez A. "Comparative trial of four antibiotic combinations for perforated appendicitis in children". Eur. J. Surg. 163: 591, (1997).

10. Sims E.H., Lou M.A., Williams S.W. et al. "Piperacillin monotherapy compared with metronidazole and gentamicin combination in penetrating abdominal trauma". J. Trauma 34: 205, (1993).

11. Chandler C.F., Lane J.S., Ferguson P. et al. "Prospective evaluation of early versus delayed laparoscopic cholecystectomy for treatment of acute cholecystitis". Am. Surg. 66: 896, (2000).

12. Van den Hazel S.J., Speelman P., Tytgat G.N.J. et al. "Role of antibiotics in the treatment and prevention of acute and recurrent cholangitis". Clin. Infect. Dis. 19: 279, (1994).

13. Shinagawa N., Yura J., Mashita K. et al. "[Bacteriological and clinical evaluation tazobactam/piperacillin in infectious diseases in surgical field]". Jpn. J. Antibiot. 48: 346, (1995).

14. Byl B., Deviere J., Struelens M.J. et al. "Antibiotic prophylaxis for infectious complications after therapeutic endoscopic retrograde cholangiopancreatography: a randomized, double-blind, placebo-controlled study". Clin. Infect. Dis. 20: 1236, (1995).

15. Morris D.L., Mojaddedi Z.J., Burdon D.W., Keighley M.R.B. "Clinical and microbiological evaluation of piperacillin in elective biliary surgery". J. Hosp. Infect. 4: 159, (1983).

16. Chan F.K., Ching J.Y., Ling T.K. et al. "Aeromonas infection in acute suppurative cholangitis: review of 30 cases". J. Infect. 40: 69, (2000).

17. de Lalla F., Scalambrino S., Tassi P.G. et al. "Piperacillin versus cefotetan as single-dose prophylaxis in abdominal hysterectomy: a prospective, randomized, multicenter study". J. Chemother. 5: 113, (1993).

18. Shah S., Mazher Y., John I.S. "Single or triple dose piperacillin prophylaxis in elective cesarean section". Int. J. Gynaecol. Obstet. 62: 23, (1998).

19. Anon. "Results of the North American trial of piperacillin/tazobactam compared with clindamycin and gentamicin in the treatment of severe intraabdominal infections. Investigators of the Piperacillin/Tazobactam Intraabdominal Infection Study Group". Eur. J. Surg. 573 (Suppl): 61, (1994).

20. Stewart M., Taylor E.W., Lindsay G. "Infection after colorectal surgery: a randomized trial of prophylaxis with piperacillin versus sulbactam/piperacillin. West of Scotland Surgical Infection Study Group". J. Hosp. Infect. 29: 135, (1995).

21. Menzel J., Bauer J., von Pritzbauer E., Klempa I. "Perioperative use of ampicillin/sulbactam, cefoxitin and piperacillin/metronidazole in elective colon and rectum surgery: a prospective and randomized quality control study in 422 patients". Int. J. Antimicrob. Agents 6 (Suppl): S79, (1996).

22. Song F., Glenny A.M. "Antimicrobial prophylaxis in colorectal surgery: a systematic review of randomized controlled trials". Br. J. Surg. 85: 1232, (1998).

23. Gribble M.J., Chow A.W., Naiman S.C. et al. "Prospective randomized trial of piperacillin monotherapy versus carboxypenicillin-aminoglycoside combination regimens in the empirical treatment of serious bacterial infections". Antimicrob. Agents Chemother. 24: 388, (1983).

24. Klastersky J. "Treatment of severe infections in patients with cancer. The role of new acyl-penicillins". Arch. Intern. Med. 142: 1984, (1982).

25. Rawlinson W., Sorrell T., Munro R. "Bacteremia in neutropenic patients at a major teaching hospital – 1981 to 1987". Aust. NZ J. Med. 18: 815, (1988).

26. Sage R., Hann I., Prentice H.G. et al. "A randomized trial of empirical antibiotic therapy with one of four beta-lactam antibiotics in combination with netilmicin in febrile neutropenic patients". J. Antimicrob. Chemother.22: 237, (1988).

27. Paul M., Soares-Weiser K., Leibovici L. "Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis". BMJ 326: 1111, (2003).

28. De Pauw B.E., Deresinski S.C., Feld R. et al. "Ceftazidime compared with piperacillin and tobramycin for the empiric treatment of fever in neutropenic patients with cancer. A multicenter randomized trial. The Intercontinental Antimicrobial Study Group". Ann. Intern. Med. 120: 834, (1994).

29. Anaissie E.J., Fainstein V., Bodey G.P. et al. "Randomized trial of betalactam regimens in febrile neutropenic cancer patients". Am. J. Med. 84: 581, (1988).

30. Ramphal R., Gucalp R., Rotstein C. et al. "Clinical experience with single agent and combination regimens in the management of infection in the febrile neutropenic patient". Am. J. Med. 100: 83S, (1996).

31. Yamamura D., Gucalp R., Carlisle P. et al. "Open randomized study of cefepime versus piperacillin-gentamicin for treatment of febrile neutropenic cancer patients. Antimicrob. Agents Chemother. 41: 1704, (1997).

32. Schiel X., Link H., Maschmeyer G. et al. "A prospective, randomized multicenter trial of the empirical addition of antifungal therapy for febrile neutropenic cancer patients: results of the Paul Ehrlich Society for Chemotherapy (PEG) Multicenter Trial II". Infection 34: 118, (2006).

33. Norrby S.R., Vandercam B., Louie T. et al. "Imipenem/cilastatin versus amikacin plus piperacillin in the treatment of infections in neutropenic patients: a prospective, randomized multi-clinic study". Scand. J. Infect. Dis. Suppl. 52: 65, (1987).

34. Vandercam B., Ezzeddine H., Agaliotis D. et al. "Imipenem/cilastatin versus piperacillin plus amikacin as empiric therapy in the treatment of febrile episodes in neutropenic patients with haematologic malignancies". Acta Clin. Belg. 44: 99, (1989).

35. Bohme A., Just-Nubling G., Bergmann L. et al. "A randomized study of imipenem compared to cefotaxime plus piperacillin as initial therapy of infections in granulocytopenic patients". Infection 23: 349, (1995).

36. Griggs J.J., Blair E.A., Norton J.R. et al. "Ciprofloxacin plus piperacillin is an equally effective regimen for empiric therapy in febrile neutropenic patients compared with standard therapy". Am. J. Hematol. 58: 293, (1998).

37. Peacock J.E., Herrington D.A., Wade J.C. et al. "Ciprofloxacin plus piperacillin compared with tobramycin plus piperacillin as empirical therapy in febrile neutropenic patients. A randomized, double-blind trial". Ann. Intern. Med. 137: 77, (2002).

38. Kelsey S.M., Wood M.E., Shaw E. et al. "A comparative study of intravenous ciprofloxacin and benzylpenicillin versus netilmicin and piperacillin for the empirical treatment of fever in neutropenic patients". J. Antimicrob. Chemother. 25: 149, (1990).

39. Tosolini F.A., Dawborn J.K., Fensling B. et al. "Clinical, microbiological and pharmacokinetic assessment of piperacillin sodium". Curr. Ther. Res. 37: 9, (1985).

40. Bodey G.P., Bolivar R., Fainstein V., Jadeja L. "Infections caused by Pseudomonas aeruginosa". Rev. Infect. Dis. 5: 279, (1983).

41. Grassi C. "Respiratory infections: Clinical evaluation". Clin. Ther. 7 (Suppl A): 45, (1985).

42. Nichols L., Maki D.G. "The emergence of resistance to beta-lactam antibiotics during treatment of Pseudomonas aeruginosa lower respiratory tract infections: Is combination therapy the solution?" Chemioterapia 4: 102, (1985).

43. Watanakunakorn C. "The use of beta-lactam antibiotics in the treatment of septicaemia and endocarditis". Scand. J. Infect. Dis. 42 (Suppl): 110, (1984).

44. Hung C.C., Chang S.C., Chen Y.C. et al. "Antibiotic therapy for Listeria monocytogenes bacteremia". J. Formos. Med. Assoc. 94: 19, (1995).

45. File Jr T.M., Tan J.S., Salstrom S.J. et al. "Timentin versus piperacillin or moxalactam in the therapy of acute bacterial infections". Antimicrob. Agents Chemother. 26: 310, (1984).

46. Link Jr A.S. "Efficacy and safety of ticarcillin plus clavulanic acid and piperacillin in patients with lower respiratory tract infections". Am. J. Med. 79: 86,  (1985).

47. Bassi O., Zuccarelli S., Amalfitano M.E. "Clinical and economic outcomes of empiric parenteral antibiotic therapy for pneumonia: a retrospective study of 1032 hospitalized patients". J. Chemother. 10: 369, (1998).

48. Aoki M., Fukao T., Kaneko H. et al. "Clinical and bacteriological evaluation of the efficacy of piperacillin in children with pneumonia". J. Infect. Chemother. 13: 224, (2007).

49. Di Modugno E., Broggio R., Erbetti I., Lowther J. "In vitro and in vivo antibacterial activities of GV129606, a new broad-spectrum trinem". Antimicrob. Agents Chemother. 41: 2742, (1997).

50. Pagliero E., Chesnel L., Hopkins J. et al. "Biochemical characterization of Streptococcus pneumoniae penicillin-binding protein 2b and its implication in beta-lactam resistance". Antimicrob. Agents Chemother. 48: 1848, (2004).

51. Mouton Y., Beuscart C., Soussy C. "[Effectiveness and tolerance of piperacillin in 333 patients]". Presse Med. 15: 2347, (1986).

52. Fournier J.L., Ramisse F., Jacolot A.C. et al. "Assessment of two penicillins plus beta-lactamase inhibitors versus cefotaxime in treatment of murine Klebsiella pneumoniae infections". Antimicrob. Agents Chemother. 40: 325, (1996).

53. Prince A.S., Neu H.C. "Use of piperacillin, a semisynthetic penicillin, in the therapy of acute exacerbations of pulmonary disease in patients with cystic fibrosis". J. Pediatr. 97: 148, (1980).

54. Macfarlane P.I., Hughes D.M., Landau L.I., Olinsky A. "The role of piperacillin therapy in pulmonary exacerbations of cystic fibrosis: a controlled study". Pediatr. Pulmonol. 1: 249, (1985).

55. Mastella G., Agostini M., Barlocco G. et al. "Alternative antibiotics for the treatment of Pseudomonas infections in cystic fibrosis. J. Antimicrob. Chemother. 12 (Suppl A): 297, (1983).

56. Avgeri S.G., Matthaiou D.K., Dimopoulos G. et al. "Therapeutic options for Burkholderia cepacia infections beyond co-trimoxazole: a systematic review of the clinical evidence". Int. J. Antimicrob. Agents 33: 394, (2009).

57. Dickinson G.M., Droller D.G., Greenman R.L., Hoffman T.A. "Clinical evaluation of piperacillin with observation on penetrability into cerebrospinal fluid". Antimicrob. Agents Chemother. 20: 481, (1981).

58. Boo N.Y., Lim V.K., Yakin F.M., Sakijan A.S. "Management of Flavobacterium meningitis in the neonates: experience with 18 consecutive cases". Singapore Med. J. 30: 177, (1989).

59. Lin C.H., Huang F.Y. "[Clinical observation of neonatal meningitis caused by flavobacterium meningosepticum]". Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 32: 171, (1991).

60. Bruel H., Chabrolle J.P., Pinon G., Poinsot J. "Neonatal meningitis caused by Alcaligenes xylosoxidans". Arch. Pediatr. 4: 260, (1997).

61. Kimura T., Aoki M., Aoki Y., Tonhyo C. "A case of sphenoid sinusitis which could be diagnosed by orbital computed tomography after detected Streptococcus pneumoniae from blood culture". Kansenshogaku Zasshi 79: 191, (2005).

62. Karpuch J., Schiffer J., Boldur I. et al. "Purulent meningitis due to Pseudomonas aeruginosa successfully treated with colistin and piperacillin". J. Infect. 11: 272, (1985).

63. Winston D.J., Ho W.G., Young L.S. et al. "Piperacillin plus amikacin therapy v carbenicillin plus amikacin therapy in febrile, granulocytopenic patients". Arch. Intern. Med. 142: 1663, (1982).

64. Lutz B.A.Z., Mogabgab W., Holmes B. et al. "Clinical evaluation of the therapeutic efficacy and tolerability of piperacillin". Antimicrob. Agents Chemother. 22: 10, (1982).

65. Rafati M.R., Rouini M.R., Mojtahedzadeh M. et al. "Clinical efficacy of continuous infusion of piperacillin compared with intermittent dosing in septic critically ill patients". Int. J. Antimicrob. Agents 28: 122, (2006).

66. Bulitta J.B., Duffull S.B., Kinzig-Schippers M. et al. "Systematic comparison of the population pharmacokinetics and pharmacodynamics of piperacillin in cystic fibrosis patients and healthy volunteers". Antimicrob. Agents Chemother. 51: 2497, (2007).

67. Thirumoorthi M.C., Asmar B.I., Buckley J.A. et al. "Pharmacokinetics of intravenously administered piperacillin in preadolescent children". J. Pediatr. 102: 941, (1983).

68. Kacet N., Roussel-Delvallez M., Gremillet C. et al. "Pharmacokinetic study of piperacillin in newborns relating to gestational and postnatal age". Pediatr. Infect. Dis. J. 11: 365, (1992).

69. Francke E.L., Appel G.B., Neu H.C. "Pharmacokinetics of intravenous piperacillin in patients undergoing chronic hemodialysis". Antimicrob. Agents Chemother. 16: 788, (1979).

70. Thompson M.I.B., Russo M.E., Matsen J.M., Atkin-Thor E. "Piperacillin pharmacokinetics in subjects with chronic renal failure". Antimicrob. Agents Chemother. 19: 450, (1981).

71. Giron J.A., Meyers B.R., Hirschman S.Z., Srulevitch E. "Pharmacokinetics of piperacillin in patients with moderate renal failure and in patients undergoing hemodialysis". Antimicrob. Agents Chemother. 19: 279, (1981).

72. De Schepper P.J., Tjandramaga T.B., Mullie A. et al. "Comparative pharmacokinetics of piperacillin in normals and in patients with renal failure". J. Antimicrob. Chemother. 9 (Suppl B): 49, (1982).

73. Debruyne D., Ryckelynck J.P., Hurault De Ligny B.M., Moulin M. "Pharmacokinetics of piperacillin in patients on peritoneal dialysis with peritonitis". J. Pharm. Sci. 79: 99, (1990).

74. Capelier G., Cornette C., Boillot A. et al. "Removal of piperacillin in critically ill patients undergoing continuous venovenous hemofiltration". Crit. Care Med. 26: 88, (1998).

75. Prince A.S., Neu H.C. "New penicillins and their use in pediatrics". Ped. Clin. N.Am. 30:3, (1983).

76. Gooding P.G., Clark B.J., Sathe S.S. "Piperacillin: a review of clinical experience". J. Antimicrob. Chemother. 9 Suppl.: 93, (1982).

77. Moscato G., Galdi E., Scibilia J. et al. "Occupational asthma, rhinitis and urticaria due to piperacillin in a pharmaceutical worker". Eur. Respir. J. 8: 467, (1995).

78. Malanga C.J., Kokontis L., Mauzy S., Bodensteiner J.B. "A Piperacillin-induced seizures". Clin. Pediatr. 36: 475, (1997).

79. Dijkmans B.A.C., Van der Meer J.W.M., Boekhout-Mussert M.J. et al. "Prolonged bleeding time during azlocillin therapy. J. Antimicrob. Chemother. 6: 554,  (1980).

80. Gentry L.O., Jamsek J.G., Natelson E.A. "Effect of sodium piperacillin on platelet function in normal volunteers". Antimicrob. Agents Chemother. 19: 532, (1981).

81. Copelan E.A., Kusumi R.K., Miller L., Fass R.J. "A comparison of the effects of mezlocillin and carbenicillin on haemostasis in volunteers". J. Antimicrob. Chemother. 11 Suppl. C: 43, (1983).

82. Ballard J.O., Barnes S.G., Sattler F.R. "Comparison of the effects of mezlocillin, carbenicillin, and placebo on normal hemostasis". Antimicrob. Agents Chemother. 25: 153, (1984).

83. Gentry L.O., Wood B.A., Natelson E.A. "Effects of apalcillin on platelet function in normal volunteers". Antimicrob. Agents Chemother. 27: 683, (1985).

84. Eykyn S.J. "Azlocillin in the treatment of serious infection with Pseudomonas aeruginosa". J. Antimicrob. Chemother.9: 395, (1982).

85. Parry M.F., Neu H.C. "The safety and tolerance of mezlocillin". J. Antimicrob. Chemother. 9 (Suppl A): 273, (1982).

86. Lang R., Lishner M., Ravid M. "Adverse reactions to prolonged treatment with high doses of carbenicillin and ureidopenicillins". Rev. Infect. Dis. 13: 68, (1991).

87. Olivera E., Lakhani P., Watanakunakorn C. "Isolated severe thrombocytopenia and bleeding caused by piperacillin". Scand. J. Infect. Dis. 24: 815, (1992).

88. Gharpure V., O’Connell B., Schiffer C.A. "Mezlocillin-induced thrombocytopenia". Ann. Intern. Med. 119: 862, (1993).

89. Scheetz M.H., McKoy J.M., Parada J.P. et al. "Systematic review of piperacillin-induced neutropenia". Drug Safety 30: 295, (2007).

90. Hayashi T., Watanabe Y., Kumano K. et al. "Protective effect of piperacillin against nephrotoxicity of cephaloridine and gentamicin in animals". Antimicrob. Agents Chemother. 32: 912, (1988).

91. Hayashi T., Watanabe Y., Kumano K. et al. "Protective effect of piperacillin against the nephrotoxicity of cisplatin in rats". Antimicrob. Agents Chemother. 33: 513, (1989).

92. Bergan T. "Overview of acylureidopenicillin pharmacokinetics". Scand. J. Infect. Dis. 29 (Suppl): 33, (1981).

93. Tjandramaga T.B., Mullie A., Verbesselt R. et al. "Piperacillin: human pharmacokinetics after intravenous and intramuscular administration". Antimicrob. Agents Chemother. 14: 829, (1978).

94. Evans M.A.L., Wilson P., Leung T., Williams J.D. "Pharmacokinetics of piperacillin following intravenous administration". J. Antimicrob. Chemother. 4: 255, (1978).

95. Wilson C.B., Koup J.R., Opheim K.E. et al. "Piperacillin pharmacokinetics in pediatric patients". Antimicrob. Agents Chemother. 22: 442, (1982).

96. Daschner F.D., Just M., Spillner G., Schlosser V. "Penetration of piperacillin into cardiac valves, subcutaneous and muscle tissue of patients undergoing open-heart surgery". J. Antimicrob. Chemother. 9: 489, (1982).

97. Goto T., Makinose S., Ohi Y. et al. "Diffusion of piperacillin, defotiam, minocycline, amikacin and ofloxacin into the prostate". Int. J. Urol. 5: 243, (1998).

98. Robinet A., Le Bot M.A., Colin J., Riche C. "Penetration of piperacillin into the vitreous after intravenous administration". Retina 18: 526, (1998).

99. Giron J.A., Meyers B.R., Hirschman S.Z. "Biliary concentrations of piperacillin in patients undergoing cholecystectomy". Antimicrob. Agents Chemother. 19: 309, (1981).

100. Russo Jr J., Thompson M.I.B., Russo M.E. et al. "Piperacillin distribution into bile, gallbladder wall, abdominal skeletal muscle, and adipose tissue in surgical patients". Antimicrob. Agents Chemother. 22: 488, (1982).

101. Blenkharn J.I., Habib N., Mok D. et al. "Decreased biliary excretion of piperacillin after percutaneous relief of extrahepatic obstructive jaundice". Antimicrob. Agents Chemother. 28: 778, (1985).

102. Heikkilä A., Erkkola R. "Pharmacokinetics of piperacillin during pregnancy". J. Antimicrob. Chemother. 28: 419, (1991).

103. Bergan T. "Pharmacokinetics of mezlocillin in healthy volunteers". Antimicrob. Agents Chemother. 14: 801, (1978).

104. Fiegel P., Becker K. "Pharmacokinetics of azlocillin in persons with normal and impaired renal functions!. Antimicrob. Agents Chemother. 14: 288, (1978).

105. Meyers B.R., Hirschman S.Z., Strougo L., Srulevitch E. "Comparative study of piperacillin, ticarcillin, and carbenicillin pharmacokinetics". Antimicrob. Agents Chemother. 17: 608, (1980).

106. Milne S.E., Waterworth P.M. "Piperacillin, a new penicillin with high antipseudomonal activity". J. Antimicrob. Chemother. 4: 247, (1978).

107. Watanakunakorn C. "Effects of inoculum size on the activity of carboxy and ureido-penicillins and effects of combinations of ureido-penicillins with aminoglycosides against resistant Pseudomonas aeruginosa". J. Antimicrob. Chemother. 17: 91, (1986).

108. Fass R.J., Barnishan J. "In vitro susceptibilities of nonfermentative Gram negative bacilli other than Pseudomonas aeruginosa to 32 antimicrobial agents". Rev. Infect. Dis. 2: 841, (1980).

109. Fass R.J. "Statistical comparison of the antibacterial activities of broad spectrum penicillins against Gram-negative bacilli". Antimicrob. Agents Chemother. 24: 156, (1983).

110. Jones R.N., Pfaller M.A., Doern G.V. et al. "Antimicrobial activity and spectrum investigation of eight broad-spectrum beta-lactam drugs: a 1997 surveillance trial in 102 medical centers in the United States". Cefepime Study Group. Diagn. Microbiol. Infect. Dis. 30: 215, (1998).

111. Lewis M.T., Yamaguchi K., Biedenbach D.J., Jones R.N. "In vitro evaluation of cefepime and other broad-spectrum beta-lactams in 22 medical centers in Japan: a phase II trial comparing two annual organism samples". The Japan Antimicrobial Resistance Study Group. Diagn. Microbiol. Infect. Dis. 35: 307, (1999).

112. Nijssen S., Florijn A., Bonten M.J. et al. "Beta-lactam susceptibilities and prevalence of ESBL-producing isolates among more than 5000 European Enterobacteriaceae isolates". Int. J. Antimicrob. Agents 24: 585, (2004).

113. Sader H.S., Biedenbach D.J., Jones R.N. "Global patterns of susceptibility for 21 commonly utilized antimicrobial agents tested against 48,440 Enterobacteriaceae in the SENTRY Antimicrobial Surveillance Program (1997–2001)". Diagn. Microbiol. Infect. Dis. 47: 361, (2003).

114. Streit J.M., Jones R.N., Sader H.S., Fritsche T.R. "Assessment of pathogen occurrences and resistance profiles among infected patients in the intensive care unit: report from the SENTRY Antimicrobial Surveillance Program (North America, 2001)". Int. J. Antimicrob. Agents 24: 111, (2004).

115. Ueo K., Fukuoka Y., Hayashi T. et al. "In vitro and in vivo antibacterial activity of T-1220, a new semisynthetic penicillin". Antimicrob. Agents Chemother. 12: 455, (1977).

116. Reeves D.S., Holt H.A., Bywater M.J., Bidwell J.L. "Comparative activity in vitro of piperacillin". J. Antimicrob. Chemother. 9 (Suppl B): 59, (1982).

117. Koehler J.M., Ashdown L.R. "In vitro susceptibilities of tropical strains of Aeromonas species from Queensland, Australia, to 22 antimicrobial agents". Antimicrob. Agents Chemother. 37: 905, (1993).

118. Overman T.L., Janda J.M. "Antimicrobial susceptibility patterns of Aeromonas jandaei, A. schubertii, A. trota, and A. veronii biotype veronii. J. Clin. Microbiol. 37: 706, (1999).

119. Mandell W.F., Garvey G.J., Neu H.C. "Achromobacter xylosoxidans bacteremia". Rev. Infect. Dis. 9: 1001, (1987).

120. Kirby J.T., Sader H.S., Walsh T.R., Jones R.N. "Antimicrobial susceptibility and epidemiology of a worldwide collection of Chryseobacterium spp.: report from the SENTRY Antimicrobial Surveillance Program (1997–2001)". J. Clin. Microbiol. 42: 445, (2004).

121. Thornsberry C., Baker C.N., Jones R.N. "In vitro antimicrobial activity of piperacillin and seven other beta-lactam antibiotics against Neisseria gonorrhoeae and Haemophilus influenzae, including beta-lactamase producing strains". J. Antimicrob. Chemother. 5: 137, (1979).

122. Rodriguez J., Fuxench-Chiesa Z, Ramirez-Ronda C.H. et al. "In vitro susceptibility of 50 non-beta-lactamase-producing Neisseria gonorrhoeae strains in 12 antimicrobial agents". Antimicrob. Agents Chemother. 23: 242, (1983).

123. Gootz T.D., Sanders C.C., Sanders Jr W.E. "In vitro activity of furazlocillin (Bay K 4999) compared with those of mezlocillin, piperacillin, and standard beta-lactam antibiotics". Antimicrob. Agents Chemother. 15: 783, (1979).

124. Robinson R.G., Saunders J., Cassel R. et al. "Comparative in vitro appraisal of piperacillin, including its activity against Salmonella typhi". Antimicrob. Agents Chemother. 18: 493, (1980).

125. Cuchural G., Jacobus N., Gorbach S.L., Tally F.P. "A survey of Bacteroides susceptibility in the United States". J. Antimicrob. Chemother. 8, (Suppl D): 27, (1981).

126. Tally F.P., Cuchural G.J., Jacobus N.V.et al. "Susceptibility of the Bacteroidies fragilis group in the United States in 1981". Antimicrob. Agents Chemother. 23: 536, (1983).

127. Tally F.P., Cuchural Jr G.J., Jacobus N.V. et al. "Nationwide study of the susceptibility of the Bacteroides fragilis group in the United States". Antimicrob. Agents Chemother. 28: 675, (1985).

128. Aldridge K.E., Ashcraft D., Cambre K. et al. "Multicenter survey of the changing in vitro antimicrobial susceptibilities of clinical isolates of Bacteroides fragilis group, Prevotella, Fusobacterium, Porphyromonas, and Peptostreptococcus species". Antimicrob. Agents Chemother. 45: 1238, (2001).

129. Goldstein E.J.C., Citron D.M., Cherubin C.E., Hillier S.L. "Comparative susceptibility of the Bacteroides fragilis group species and other anaerobic bacteria to meropenem, imipenem, piperacillin, cefoxitin, ampicillin/sulbactam, clindamycin and metronidazole". J. Antimicrob. Chemother. 31: 363, (1993).

130. Dickinson G.M., Clearly T.J., Hoffman T.A. "Comparative evaluation of piperacillin in vitro". Antimicrob. Agents Chemother. 14: 919, (1978).

131. Alcaide F., Linares J., Pallares R. et al. "In vitro activities of 22 beta-lactam antibiotics against penicillin-resistant and penicillin-susceptible viridans group streptococci isolated from blood". Antimicrob. Agents Chemother. 39: 2243, (1995).

132. Appelbaum P.C., Spangler S.K., Jacobs M.R. "Susceptibilities of 394 Bacteroides fragilis, non-B. fragilis group Bacteroides species, and Fusobacterium
species to newer antimicrobial agents". Antimicrob. Agents Chemother. 35: 1214, (1991).

133. Chow A.W., Cheng N., Bartlett K.H. "In vitro susceptibility of Clostridium difficile to new beta-lactam and quinolone antibiotics". Antimicrob. Agents Chemother. 28: 842, (1985).

134. Bowie W.R. "Lack of in vitro activity of cefoxitin, cefamandole, cefuroxime and piperacillin against Chlamydia trachomatis". Antimicrob. Agents Chemother. 21: 339, (1982).

135. Pankuch G.A., Visalli M.A., Jacobs M.R., Appelbaum P.C. "Activities of oral and parenteral agents against penicillin-susceptible and -resistant pneumococci". Antimicrob.  Agents Chemother. 39: 1499, (1995).

136. Jones R.N., Barry A.L. "Studies to optimize the in vitro testing of piperacillin combined with tazobactam (YTR 830)". Diagn. Microbiol. Infect. Dis. 12: 495, (1989).

137. Verbist L. "In vitro activity of piperacillin, a new semisynthetic penicillin with an unusually broad spectrum of activity". Antimicrob. Agents Chemother. 13: 349, (1978).

138. Dornbusch K., the European Study Group on Antibiotic Resistance (1990).
"Resistance to beta-lactam antibiotics and ciprofloxacin in Gram-negative bacilli and staphylococci isolated from blood: a European collaborative study". J. Antimicrob. Chemother. 26: 269, (1990).

139. Pfaller M.A., Jones R.N., Marshall S.A. et al. "Inducible amp C betalactamase producing gram-negative bacilli from blood stream infections: frequency, antimicrobial susceptibility, and molecular epidemiology in a national surveillance program (SCOPE)". Diagn. Microbiol. Infect. Dis. 28: 211, (1997).

140. Bell J.M., Chitsaz M., Turnidge J.D. et al. "Prevalence and significance of a negative extended-spectrum beta-lactamase (ESBL) confirmation test result after a positive ESBL screening test result for isolates of Escherichia coli and Klebsiella pneumoniae: results from the SENTRY Asia-Pacific Surveillance Program". J. Clin. Microbiol. 45: 1478, (2007).

141. Godfrey A.J., Bryan L.E., Rabin H.R. "Beta-lactam-resistant Pseudomonas aeruginosa with modified penicillin-binding proteins emerging during cystic fibrosis treatment". Antimicrob. Agents Chemother. 19: 705, (1981).

142. Bell S.M., Pham J.N., Lanzarone J.Y.M. "Mutation of Pseudomonas aeruginosa to piperacillin resistance mediated by beta-lactamase production". J. Antimicrob. Chemother. 15: 665, (1985).

143. Fujita J., Negayama K., Takigawa K. et al. "Activity of antibiotics against resistant Pseudomonas aeruginosa". J. Antimicrob. Chemother. 29: 539, (1992).

144. Mesaros N., Nordmann P., Plesiat P. et al. "Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium". Clin. Microbiol. Infect. 13: 560, (2007).

145. Empey K.M., Rapp R.P., Evans M.E. "The effect of an antimicrobial formulary change on hospital resistance patterns". Pharmacotherapy 22: 81, (2002).

146. Martinez J.A., Delgado E., Marti S. et al. "Influence of antipseudomonal agents on Pseudomonas aeruginosa colonization and acquisition of resistance in critically ill medical patients". Intens. Care Med. 35: 439, (2009).

147. Radberg G., Nilsson L.E., Svensson S. "Development of quinolone imipenem cross resistance in Pseudomonas aeruginosa during exposure to ciprofloxacin". Antimicrob. Agents Chemother. 34: 2142, (1990).

148. Wu Y.L., Scott E.M., Po A.L., Tariq V.N. "Development of resistance and cross-resistance in Pseudomonas aeruginosa exposed to subinhibitory antibiotic concentrations". APMIS 107: 585, (1999).

149. Kriengkauykiat J., Porter E., Lomovskaya O., Wong-Beringer A. "Use of an efflux pump inhibitor to determine the prevalence of efflux pump-mediated fluoroquinolone resistance and multidrug resistance in Pseudomonas aeruginosa". Antimicrob. Agents Chemother. 49: 565, (2005).

150. Brunner M., Pernerstorfer T., Mayer B.X. et al. "Surgery and intensive care procedures affect the target site distribution of piperacillin". Crit. Care Med. 28: 1754, (2000).

151. Sauermann R., Zeitlinger M., Erovic B.M. et al. "Pharmacodynamics of pipetracillin in severely ill patients evaluated by using a PK/PD model". Int. J. Antimicrob. Agents 22: 574,. (2003).





     Hit Counter


Send mail to stefano.biondi@innovativesolution.it with questions or comments about this web site.
Copyright © 2010 Innovative Solution di Biondi Stefano