Zerbaxa Mechanism of Action

Pharmacology: Mechanism of Action: ZERBAXA is an antibacterial drug [see Microbiology as follows].
Pharmacodynamics: As with other beta-lactam antibacterial agents, the percent time of dosing interval that the plasma concentration of ceftolozane exceeds the minimum inhibitory concentration (MIC) of the infecting organism has been shown to be the best predictor of efficacy in animal models of infection. The percent time of dosing interval that the plasma concentration of tazobactam exceeds a threshold concentration has been determined to be the parameter that best predicts the efficacy of tazobactam in in vitro and in vivo models. The exposure-response analyses in efficacy and safety clinical trials for cIAI, cUTI, and HABP/VABP support the recommended dose regimens of ZERBAXA.
Cardiac Electrophysiology: In a randomized, positive and placebo-controlled crossover thorough QTc study, 51 healthy subjects were administered a single therapeutic dose of ZERBAXA 1.5 gram (ceftolozane 1 g and tazobactam 0.5 g) and a supratherapeutic dose of ZERBAXA 4.5 gram (ceftolozane 3 g and tazobactam 1.5 g). No significant effects of ZERBAXA on heart rate, electrocardiogram morphology, PR, QRS, or QT interval were detected.
Clinical Studies: Complicated Intra-abdominal Infections: A total of 979 adults hospitalized with cIAI were randomized and received study medications in a multinational, double-blind study comparing ZERBAXA 1.5 g (ceftolozane 1 g and tazobactam 0.5 g) intravenously every 8 hours plus metronidazole (500 mg intravenously every 8 hours) to meropenem (1 g intravenously every 8 hours) for 4 to 14 days of therapy. Complicated intra-abdominal infections included appendicitis, cholecystitis, diverticulitis, gastric/duodenal perforation, perforation of the intestine, and other causes of intra-abdominal abscesses and peritonitis. The majority of patients (75%) were from Eastern Europe; 6.3% were from the United States.
The primary efficacy endpoint was clinical response, defined as complete resolution or significant improvement in signs and symptoms of the index infection at the test-of-cure (TOC) visit which occurred 24 to 32 days after the first dose of study drug. The primary efficacy analysis population was the microbiological intent-to-treat (MITT) population, which included all patients who had at least 1 baseline intra-abdominal pathogen regardless of the susceptibility to study drug. The key secondary efficacy endpoint was clinical response at the TOC visit in the microbiologically evaluable (ME) population, which included all protocol-adherent MITT patients.
The MITT population consisted of 806 patients; the median age was 52 years and 57.8% were male. The most common diagnosis was appendiceal perforation or peri-appendiceal abscess, occurring in 47% of patients. Diffuse peritonitis at baseline was present in 34.2% of patients.
ZERBAXA plus metronidazole was non-inferior to meropenem with regard to clinical cure rates at the TOC visit in the MITT population. Clinical cure rates at the TOC visit are displayed by patient population in Table 1. Clinical cure rates at the TOC visit by pathogen in the MITT population are presented in Table 2. (See Tables 1 and 2.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

In a subset of the E. coli and K. pneumoniae isolates from both arms of the cIAI Phase 3 trial that met pre-specified criteria for beta-lactam susceptibility, genotypic testing identified certain ESBL groups (e.g., TEM, SHV, CTX-M, OXA) in 53/601 (9%). Cure rates in this subset were similar to the overall trial results. In vitro susceptibility testing showed that some of these isolates were susceptible to ZERBAXA (MIC ≤ 2 mcg/mL), while some others were not susceptible (MIC >2 mcg/mL). Isolates of a specific genotype were seen in patients who were deemed to be either successes or failures.
Complicated Urinary Tract Infections, Including Pyelonephritis: A total of 1068 adults hospitalized with cUTI (including pyelonephritis) were randomized and received study medications in a multinational, double-blind study comparing ZERBAXA 1.5 g (ceftolozane 1 g and tazobactam 0.5 g) intravenously every 8 hours to levofloxacin (750 mg intravenously once daily) for 7 days of therapy. The primary efficacy endpoint was defined as complete resolution or marked improvement of the clinical symptoms and microbiological eradication (all uropathogens found at baseline at ≥10⁵ were reduced to <10⁴ CFU/mL) at the test-of-cure (TOC) visit 7 (± 2) days after the last dose of study drug. The primary efficacy analysis population was the microbiologically modified intent-to-treat (mMITT) population, which included all patients who received study medication and had at least 1 baseline uropathogen. The key secondary efficacy endpoint was the composite microbiological and clinical cure response at the TOC visit in the microbiologically evaluable (ME) population, which included protocol-adherent mMITT patients with a urine culture at the TOC visit.
The mMITT population consisted of 800 patients with cUTI, including 656 (82%) with pyelonephritis. The median age was 50.5 years and 74% were female. Concomitant bacteremia was identified in 62 (7.8%) patients at baseline; 608 (76%) patients were enrolled in Eastern Europe and 14 (1.8%) patients were enrolled in the United States.
ZERBAXA demonstrated efficacy with regard to the composite endpoint of microbiological and clinical cure at the TOC visit in both the mMITT and ME populations (Table 3). Composite microbiological and clinical cure rates at the TOC visit by pathogen in the mMITT population are presented in Table 4.
In the mMITT population, the composite cure rate in ZERBAXA-treated patients with concurrent bacteremia at baseline was 23/29 (79.3%).
Although a statistically significant difference was observed in the ZERBAXA arm compared to the levofloxacin arm with respect to the primary endpoint, it was likely attributable to the 212/800 (26.5%) patients with baseline organisms non-susceptible to levofloxacin. Among patients infected with a levofloxacin-susceptible organism at baseline, the response rates were similar (Table 3). (See Tables 3 and 4.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

In a subset of the E. coli and K. pneumoniae isolates from both arms of the cUTI Phase 3 trial that met pre-specified criteria for beta-lactam susceptibility, genotypic testing identified certain ESBL groups (e.g., TEM, SHV, CTX-M, OXA) in 104/687 (15%). Cure rates in this subset were similar to the overall trial results. In vitro susceptibility testing showed that some of these isolates were susceptible to ZERBAXA (MIC ≤2 mcg/mL), while some others were not susceptible (MIC >2 mcg/mL). Isolates of a specific genotype were seen in patients who were deemed to be either successes or failures.
Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP): A total of 726 adult patients hospitalized with HABP/VABP were enrolled in a multinational, double-blind study (NCT02070757) comparing ZERBAXA 3 g (ceftolozane 2 g and tazobactam 1 g) intravenously every 8 hours to meropenem (1 g intravenously every 8 hours) for 8 to 14 days of therapy. All patients had to be intubated and on mechanical ventilation at randomization.
Efficacy was assessed based on all-cause mortality at Day 28 and clinical cure, defined as complete resolution or significant improvement in signs and symptoms of the index infection at the test-of-cure (TOC) visit which occurred 7 to 14 days after the end of treatment. The analysis population was the intent-to-treat (ITT) population, which included all randomized patients.
Following a diagnosis of HABP/VABP and prior to receipt of first dose of study drug, if required, patients could have received up to a maximum of 24 hours of active non-study antibacterial drug therapy in the 72 hours preceding the first dose of study drug. Patients who had failed prior antibacterial drug therapy for the current episode of HABP/VABP could be enrolled if the baseline lower respiratory tract (LRT) culture showed growth of a Gram-negative pathogen while the patient was on the antibacterial therapy and all other eligibility criteria were met. Empiric therapy at baseline with linezolid or other approved therapy for Gram-positive coverage was required in all patients pending baseline LRT culture results. Adjunctive Gram-negative therapy was optional and allowed for a maximum of 72 hours in centers with a prevalence of meropenem-resistant P. aeruginosa more than 15%.
Of the 726 patients in the ITT population, the median age was 62 years and 44% of the population was 65 years of age and older, with 22% of the population 75 years of age and older. The majority of patients were white (83%), male (71%) and were from Eastern Europe (64%). The median APACHE II score was 17 and 33% of subjects had a baseline APACHE II score of greater than or equal to 20. All subjects were on mechanical ventilation and 519 (71%) had VABP. At randomization, 92% of subjects were in the ICU, 77% had been hospitalized for 5 days or longer, and 49% were ventilated for 5 days or longer. A total of 258 of 726 (36%) patients had CrCl less than 80 mL/min at baseline; among these, 99 (14%) had CrCl less than 50 mL/min. Patients with end-stage renal disease (CrCl less than 15 mL/min) were excluded from the trial. Approximately 13% of subjects were failing their current antibacterial drug therapy for HABP/VABP, and bacteremia was present at baseline in 15% of patients. Key comorbidities included diabetes mellitus, congestive heart failure, and chronic obstructive pulmonary disease at rates of 22%, 16%, and 12%, respectively. In both treatment groups, most subjects (63.1%) received between 8 and 14 days of study therapy as specified in the protocol.
Table 5 presents the results for Day 28 all-cause mortality and clinical cure at the TOC visit overall and by ventilated HABP and VABP. (See Table 5.)

Click on icon to see table/diagram/image

In the ITT population, Day 28 all-cause mortality and clinical cure rates in patients with CrCl greater than or equal to 150 mg/mL were similar between ZERBAXA and meropenem. In patients with bacteremia at baseline, Day 28 all-cause mortality rates were 23/64 (35.9%) for ZERBAXA-treated patients and 13/41 (31.7%) for meropenem-treated patients; clinical cure rates were 30/64 (46.9%) and 15/41 (36.6%), respectively.
Per pathogen Day 28 all-cause mortality and clinical cure at TOC were assessed in the microbiologic intention to treat population (mITT), which consisted of all randomized subjects who had a baseline lower respiratory tract (LRT) pathogen that was susceptible to both study treatments. In the mITT population, Klebsiella pneumoniae (113/425, 26.6%) and Pseudomonas aeruginosa (103/425, 24.2%) were the most prevalent pathogens isolated from baseline LRT cultures.
Day 28 all-cause mortality and clinical cure rates at TOC by pathogen in the mITT population are presented in Table 6. In the mITT population, clinical cure rates in patients with a Gram-negative pathogen at baseline were 139/215 (64.7%) for ZERBAXA and 115/204 (56.4%) for meropenem, respectively. (See Table 6.)

Click on icon to see table/diagram/image

In a subset of Enterobacteriaceae isolates from both arms of the trial that met pre-specified criteria for beta-lactam susceptibility, genotypic testing identified certain ESBL groups (e.g., TEM, SHV, CTX-M, OXA) in 101/425 (23.8%). Day 28 all-cause mortality and clinical cure rates in this subset were similar to the overall trial results.
Pharmacokinetics: Ceftolozane and tazobactam pharmacokinetics are similar following single- and multiple-dose administrations. The C_max and AUC of ceftolozane and tazobactam increase in proportion to dose.
The mean steady-state population pharmacokinetic parameters of ZERBAXA in patients with cIAI and cUTI receiving 1-hour intravenous infusions of ZERBAXA 1.5 g (ceftolozane 1 g and tazobactam 0.5 g) or patients with HABP/VABP receiving 1-hour intravenous infusions of ZERBAXA 3 g (ceftolozane 2 g and tazobactam 1 g) every 8 hours are summarized in Table 7. (See Table 7.)

Click on icon to see table/diagram/image

Distribution: The binding of ceftolozane and tazobactam to human plasma proteins is approximately 16% to 21% and 30%, respectively. The mean (CV%) steady-state volume of distribution of ZERBAXA in healthy adult males (n = 51) following a single intravenous dose of ZERBAXA 1.5 g (ceftolozane 1 g and tazobactam 0.5 g) was 13.5 L (21%) and 18.2 L (25%) for ceftolozane and tazobactam, respectively, similar to extracellular fluid volume.
Following 1-hour intravenous infusions of ZERBAXA 3 g (ceftolozane 2 g and tazobactam 1 g) or adjusted based on renal function every 8 hours in ventilated patients with confirmed or suspected pneumonia (N=22), mean pulmonary epithelial lining fluid-to-free plasma AUC ratios of ceftolozane and tazobactam were approximately 50% and 62%, respectively, and are similar to those in healthy subjects (approximately 61% and 63%, respectively) receiving ZERBAXA 1.5 g (ceftolozane 1 g and tazobactam 0.5 g). Minimum ceftolozane and tazobactam epithelial lung lining fluid concentrations in ventilated subjects at the end of the dosing interval were 8.2 mcg/mL and 1.0 mcg/mL, respectively.
Elimination: Ceftolozane is eliminated from the body by renal excretion with a mean half-life of approximately 3 to 4 hours. Tazobactam is eliminated by renal excretion and metabolism with a plasma mean half-life of approximately 2 to 3 hours. The elimination half-life (t_1/2) of ceftolozane or tazobactam is independent of dose.
Metabolism: Ceftolozane does not appear to be metabolized to any appreciable extent and is not a substrate for CYP enzymes. The beta-lactam ring of tazobactam is hydrolyzed to form the pharmacologically inactive tazobactam metabolite M1.
Excretion: Ceftolozane, tazobactam and the tazobactam metabolite M1 are excreted by the kidneys. Following administration of a single ZERBAXA 1.5 g (ceftolozane 1 g and tazobactam 0.5 g) intravenous dose to healthy male adults, greater than 95% of ceftolozane was excreted in the urine as unchanged parent drug. More than 80% of tazobactam was excreted as the parent compound with the remainder excreted as the tazobactam M1 metabolite. After a single dose of ZERBAXA, renal clearance of ceftolozane (3.41 - 6.69 L/h) was similar to plasma CL (4.10 to 6.73 L/h) and similar to the glomerular filtration rate for the unbound fraction, suggesting that ceftolozane is eliminated by the kidney via glomerular filtration. Tazobactam is a substrate for OAT1 and OAT3 transporters and its elimination has been shown to be inhibited by probenecid, an inhibitor of OAT1/3.
Specific Populations: Dose adjustment is not warranted on the basis of age (18 years and older), gender, or race/ethnicity. No significant differences in the pharmacokinetics of ceftolozane and tazobactam were observed based on age (18 years and older), gender, weight, or race/ethnicity.
Patients with Renal Impairment: The ceftolozane dose normalized geometric mean AUC increased up to 1.26-fold, 2.5-fold, and 5-fold in subjects with CrCl 80-51 mL/min, 50-30 mL/min, and 29-15 mL/min, respectively, compared to healthy subjects with normal renal function. The respective tazobactam dose normalized geometric mean AUC increased approximately up to 1.3-fold, 2-fold, and 4-fold. To maintain similar systemic exposures to those with normal renal function, dosage adjustment is required [see Dosage Adjustments in Patients with Renal Impairment under Dosage & Administration].
In subjects with ESRD on HD, approximately two-thirds of the administered ZERBAXA dose is removed by HD. A single loading dose of ZERBAXA followed by a maintenance dose administered every 8 hours for the remainder of the treatment period is recommended in patients with ESRD on HD. On HD days, administer the dose at the earliest possible time following completion of HD. [See Dosage Adjustments in Patients with Renal Impairment under Dosage & Administration.]
Patients with Augmented Renal Function: Following a single 1-hour intravenous infusion of ZERBAXA 3 g (ceftolozane 2 g and tazobactam 1 g) to critically-ill patients with CrCl greater than or equal to 180 mL/min (N=10), mean terminal half-life values of ceftolozane and tazobactam were 2.6 hours and 1.5 hours, respectively. No dose adjustment of ZERBAXA is recommended for HABP/VABP patients with augmented renal function [see Pharmacodynamics: Clinical Studies: Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) as previously mentioned].
Patients with Hepatic Impairment: As ZERBAXA does not undergo hepatic metabolism, the systemic clearance of ZERBAXA is not expected to be affected by hepatic impairment.
No dose adjustment is recommended for ZERBAXA in subjects with hepatic impairment.
Geriatric Patients: In a population pharmacokinetic analysis of ZERBAXA, no clinically relevant differences in exposure were observed with regard to age.
No dose adjustment of ZERBAXA based on age is recommended. Dosage adjustment for ZERBAXA in geriatric patients should be based on renal function [see Dosage Adjustments in Patients with Renal Impairment under Dosage & Administration].
Pediatric Patients: Safety and effectiveness in pediatric patients have not been established.
Drug Interactions: No drug-drug interaction was observed between ceftolozane and tazobactam in a clinical study in 16 healthy subjects. In vitro and in vivo data indicate that ZERBAXA is unlikely to cause clinically relevant drug-drug interactions related to CYPs and transporters at therapeutic concentrations.
Drug Metabolizing Enzymes: In vivo data indicated that ZERBAXA is not a substrate for CYPs. Thus, clinically relevant drug-drug interactions involving inhibition or induction of CYPs by other drugs are unlikely to occur.
In vitro studies demonstrated that ceftolozane, tazobactam and the M1 metabolite of tazobactam did not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 and did not induce CYP1A2, CYP2B6, or CYP3A4 at therapeutic plasma concentrations. In vitro induction studies in primary human hepatocytes demonstrated that ceftolozane, tazobactam, and the tazobactam metabolite M1 decreased CYP1A2 and CYP2B6 enzyme activity and mRNA levels in primary human hepatocytes as well as CYP3A4 mRNA levels at supratherapeutic plasma concentrations. Tazobactam metabolite M1 also decreased CYP3A4 activity at supratherapeutic plasma concentrations. A clinical drug-drug interaction study was conducted and results indicated drug interactions involving CYP1A2 and CYP3A4 inhibition by ZERBAXA are not anticipated.
Membrane Transporters: Ceftolozane and tazobactam were not substrates for P-gp or BCRP, and tazobactam was not a substrate for OCT2, in vitro at therapeutic concentrations.
Tazobactam is a known substrate for OAT1 and OAT3. Co-administration of tazobactam with the OAT1/OAT3 inhibitor probenecid has been shown to prolong the half-life of tazobactam by 71%. Co-administration of ZERBAXA with drugs that inhibit OAT1 and/or OAT3 may increase tazobactam plasma concentrations.
In vitro data indicate that ceftolozane did not inhibit P-gp, BCRP, OATP1B1, OATP1B3, OCT1, OCT2, MRP, BSEP, OAT1, OAT3, MATE1, or MATE2-K in vitro at therapeutic plasma concentrations.
In vitro data indicate that neither tazobactam nor the tazobactam metabolite M1 inhibit P-gp, BCRP, OATP1B1, OATP1B3, OCT1, OCT2, or BSEP transporters at therapeutic plasma concentrations. In vitro, tazobactam inhibited human OAT1 and OAT3 transporters with IC₅₀ values of 118 and 147 mcg/mL, respectively. A clinical drug-drug interaction study was conducted and results indicated clinically relevant drug interactions involving OAT1/OAT3 inhibition by ZERBAXA are not anticipated.
Toxicology: Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term carcinogenicity studies in animals have not been conducted with ZERBAXA, ceftolozane, or tazobactam.
ZERBAXA was negative for genotoxicity in an in vitro mouse lymphoma assay and an in vivo rat bone-marrow micronucleus assay. In an in vitro chromosomal aberration assay in Chinese hamster ovary cells, ZERBAXA was positive for structural aberrations.
Ceftolozane was negative for genotoxicity in an in vitro microbial mutagenicity (Ames) assay, an in vitro chromosomal aberration assay in Chinese hamster lung fibroblast cells, an in vitro mouse lymphoma assay, an in vitro HPRT assay in Chinese hamster ovary cells, an in vivo mouse micronucleus assay, and an in vivo unscheduled DNA synthesis (UDS) assay.
Tazobactam was negative for genotoxicity in an in vitro microbial mutagenicity (Ames) assay, an in vitro chromosomal aberration assay in Chinese hamster lung cells, an in vitro mammalian point-mutation (Chinese hamster ovary cell HPRT) assay, an in vivo mouse bone-marrow micronucleus assay, and an in vivo UDS assay.
Ceftolozane was administered in a fertility study at intravenous doses of 100, 300, and 1000 mg/kg/day to male rats for 28 days before mating and through the mating period and to female rats for 14 days before mating, through the mating period, and until the 7th day of gestation. Ceftolozane had no adverse effect on fertility in male or female rats at doses up to 1000 mg/kg/day (approximately 1.4 times the maximum recommended human dose (MRHD) of 2 grams every 8 hours based on AUC comparison).
In a rat fertility study, intraperitoneal tazobactam doses of 40, 160, and 640 mg/kg/day were administered twice-daily to male rats beginning 70 days before mating and through the mating period, and to female rats beginning 14 days before mating, during the mating period, and until Gestation Day 21. Male and female fertility parameters were not affected at doses less than or equal to 640 mg/kg/day (approximately 2 times the MRHD of 1 gram every 8 hours based on body surface comparison).
Microbiology: Mechanism of Action: Ceftolozane belongs to the cephalosporin class of antibacterial drugs. The bactericidal action of ceftolozane results from inhibition of cell wall biosynthesis, and is mediated through binding to penicillin-binding proteins (PBPs). Ceftolozane is an inhibitor of PBPs of P. aeruginosa (e.g., PBP1b, PBP1c, and PBP3) and E. coli (e.g., PBP3).
Tazobactam sodium has little clinically relevant in vitro activity against bacteria due to its reduced affinity to penicillin-binding proteins. It is an irreversible inhibitor of some beta-lactamases (e.g., certain penicillinases and cephalosporinases), and can bind covalently to some chromosomal and plasmid-mediated bacterial beta-lactamases.
Resistance: Mechanisms of beta-lactam resistance may include the production of beta-lactamases, modification of PBPs by gene acquisition or target alteration, up-regulation of efflux pumps, and loss of outer membrane porin.
Clinical isolates may produce multiple beta-lactamases, express varying levels of beta-lactamases, or have amino acid sequence variations, and other resistance mechanisms that have not been identified.
Culture and susceptibility information and local epidemiology should be considered in selecting or modifying antibacterial therapy.
ZERBAXA demonstrated in vitro activity against Enterobacteriaceae in the presence of some extended-spectrum beta-lactamases (ESBLs) and other beta-lactamases of the following groups: TEM, SHV, CTX-M, and OXA. ZERBAXA is not active against bacteria that produce serine carbapenemases [K. pneumoniae carbapenemase (KPC)], and metallo-beta-lactamases.
In ZERBAXA clinical trials, some isolates of Enterobacteriaceae with minimum inhibitory concentration to ZERBAXA of ≤2 mcg/mL produced beta-lactamases. These isolates produced one or more beta-lactamases of the following enzyme groups: CTX-M, OXA, TEM, or SHV.
Some of these beta-lactamases were also produced by isolates of Enterobacteriaceae with minimum inhibitory concentration to ZERBAXA >2 mcg/mL.
ZERBAXA demonstrated in vitro activity against P. aeruginosa isolates tested that had chromosomal AmpC, loss of outer membrane porin (OprD), or up regulation of efflux pumps (MexXY, MexAB).
Isolates resistant to other cephalosporins may be susceptible to ZERBAXA, although cross-resistance may occur.
Interaction with Other Antimicrobials: In vitro synergy studies suggest no antagonism between ZERBAXA and other antibacterial drugs (e.g., meropenem, amikacin, aztreonam, levofloxacin, tigecycline, rifampin, linezolid, daptomycin, vancomycin, and metronidazole).
Antimicrobial Activity: ZERBAXA has been shown to be active against the following bacteria, both in vitro and in clinical infections [see Indications/Uses].
Complicated Intra-abdominal Infections: Gram-negative bacteria: Enterobacter cloacae; Escherichia coli; Klebsiella oxytoca; Klebsiella pneumoniae; Proteus mirabilis; Pseudomonas aeruginosa.
Gram-positive bacteria: Streptococcus anginosus; Streptococcus constellatus; Streptococcus salivarius.
Complicated Urinary Tract Infections, Including Pyelonephritis: Gram-negative bacteria: Escherichia coli; Klebsiella pneumoniae; Proteus mirabilis.
Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP): Gram-negative bacteria: Enterobacter cloacae; Escherichia coli; Haemophilus influenzae; Klebsiella oxytoca; Klebsiella pneumoniae; Proteus mirabilis; Pseudomonas aeruginosa; Serratia marcescens.
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ceftolozane and tazobactam against isolates of similar genus or organism group. However, the efficacy of ZERBAXA in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials.
Gram-negative bacteria: Citrobacter koseri; Klebsiella aerogenes; Morganella morganii; Proteus vulgaris; Serratia liquefaciens.