This is a Phase 1, single-center, multi-arm, open-label, randomized, three-period, crossover study to evaluate the drug-drug interaction, pharmacokinetics, safety, and tolerability of a single dose of SPR741 combined with each of 3 different partner antibiotics (ceftazidime or piperacillin/tazobactam or aztreonam) in healthy volunteers. Participants will be administered single doses of SPR741 alone, a single dose of SPR741 in combination with 1 of 3 different partner antibiotics, and the partner antibiotic alone in a randomized sequence. Twenty-seven (27) adult male and female normal healthy participants 18 to 55 years of age are planned to participate in the study. Women of childbearing potential will not be eligible to participate.

This is a Phase 1, single-center, multi-arm, open-label, randomized, three-period crossover study to evaluate the drug-drug interaction, pharmacokinetics, safety, and tolerability of a single dose of SPR741 combined with each of 3 different partner antibiotics (ceftazidime, piperacillin/tazobactam, and aztreonam) in healthy volunteers. Participants will be administered a single dose of SPR741 alone, a single dose of SPR741 in combination with 1 of the 3 different partner antibiotics, and a single dose of the partner antibiotic alone in a randomized sequence. Twenty-seven (27) adult male and female normal healthy participants 18 to 55 years of age are planned to participate in the study. Women of childbearing potential will not be eligible to participate. The study will consist of 3 phases: a screening phase, a treatment phase, and a follow-up phase.

The 3 treatment arms will be enrolled and dosed in parallel or in a staggered manner, as needed for scheduling.

All participants in the study will be monitored for safety after administration of the last dose of investigational product.

Inclusion Criteria:

1. Healthy adult males and/or females (of non-childbearing potential), 18 to 55 years of age (inclusive) at the time of screening;

2. BMI ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive);

3. Medically healthy without clinically significant abnormalities at the screening visit or Day -1, including:

   1. Physical examination, vital signs. Vital signs include temperature, heart rate, respiratory rate, and blood pressure;
   2. Triplicate ECGs taken at least 1 minute apart with QTcF interval duration less than 450 msec obtained as an average from the triplicate screening and pre-dose Day 1 ECGs after at least 5 min in a semi-supine quiet rest;
   3. Hemoglobin/hematocrit, white blood cell (WBC) count, and platelet count equal to or greater than the lower limit of normal range of the reference laboratory;
   4. Creatinine, BUN, ALT and AST equal to or less than the upper limit of normal for the reference laboratory; results of all other clinical chemistry and urine analytes without any clinically significant abnormality.

   Discussion between the PI and the Medical Monitor (MM) is encouraged regarding the potential significance of any laboratory value that is outside of the normal range during the pre-dose period.

4. Be non-smokers (including tobacco, e-cigarettes or marijuana) for at least 1 month prior to participation in the study;

5. Willing and able to provide written informed consent;

6. Be willing and able to comply with all study assessments and adhere to the protocol schedule;

7. Have suitable venous access for drug administration and blood sampling;

8. If female, be of non-childbearing potential (e.g. post-menopausal as demonstrated by FSH or surgical sterilization i.e., tubal ligation or hysterectomy). Provision of documentation is not required for female sterilization, verbal confirmation is adequate;

9. If male, a willingness not to donate sperm and if engaging in sexual intercourse with a female partner who could become pregnant, a willingness to use a condom in addition to having the female partner use a highly effective method of birth control (such as an intrauterine device, diaphragm, oral contraceptives, injectable progesterone, subdermal implants, or a tubal ligation). This criterion applies to males (and/or female partners) who are surgically sterile and must be followed from the time of first study drug administration until 90 days after the final administration of study drug.

Exclusion Criteria:

1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past 3 months determined by the PI to be clinically relevant;
2. History of known or suspected Clostridium difficile infection;
3. History of seizure disorders;
4. Positive urine drug/alcohol testing at screening or check-in (Day -1);
5. Positive testing for HIV, HBsAg or HCV;
6. History of substance abuse or alcohol abuse (defined as those who consume more than 14 units of alcohol per week, and where this consumption is spread over less than 3 days, or those who regularly (weekly) consumed excessive amounts of alcohol (>8 units for men and >6 units for women in one consumption, excessive amounts as defined by the UK National Office of Statistics) within the previous 5 years;
7. Use of any prescription medication or any over-the-counter medication, herbal products, vitamins, diet aids or hormone supplements within 7 days prior to randomisation;
8. Documented hypersensitivity reaction or anaphylaxis to any medication;
9. Donation of blood or plasma within 30 days prior to randomisation, or loss of whole blood of more than 500 mL within 30 days prior to randomisation, or receipt of a blood transfusion within 1 year of study enrollment;
10. Participation in a New Chemical Entity clinical study within the previous 3 months or a marketed drug clinical study within the 30 days before the first dose of IMP. (Washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study).
11. Any other condition or prior therapy, which, in the opinion of the PI, would make the volunteer unsuitable for this study, including unable to cooperate fully with the requirements of the study protocol or likely to be non-compliant with any study requirements.