eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease
Urinary Tract Infection: Treatment & Medication
Updated: Nov 23, 2009
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- Differential Diagnoses & Workup
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Treatment
Medical Care
- Infants younger than 8 weeks with a febrile urinary tract infection (UTI)
- The diagnosis is usually based on fever and positive results form a urine specimen obtained by catheterization. Infants with such findings are usually hospitalized and receive parenteral antibiotic therapy (see Table 3 below). However, clinical judgment may indicate that home treatment is appropriate. Parenteral antibiotics may be used with daily follow-up until the patient is afebrile for 24 hours. Complete 10-14 days of therapy with an oral antibiotic active against the infecting bacteria.
- Table 3. Antibiotic Agents for Parenteral Treatment of a Urinary Tract Infection
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[ CLOSE WINDOW ]Table
Drug Dosage and Route Comment Ceftriaxone 50-75 mg/kg/d IV/IM as a single dose or divided q12h Do not use in infants <6 wk of age; parenteral antibiotic with long half-life; may displace bilirubin from albumin Cefotaxime 150 mg/kg/d IV/IM divided q6-8h Safe to use in infants <6 wk of age; used with ampicillin in infants aged 2-8 wk Ampicillin 100 mg/kg/d IV/IM divided q8h Used with gentamicin in neonates <2 wk of age; for enterococci and patients allergic to cephalosporins Gentamicin Term neonates <7 d: 3.5-5 mg/kg/dose IV q24h
Infants and children <5 y: 2.5 mg/kg/dose IV q8h or single daily dosing with normal renal function of 5-7.5 mg/kg/dose IV q24h
Children >5 y: 2-2.5 mg/kg/dose IV q8h or single daily dosing with normal renal function of 5-7.5 mg/kg/dose IV q24hMonitor blood levels and kidney function if therapy extends >48 h Note.—IM = intramuscular; IV = intravenous; q = every.Drug Dosage and Route Comment Ceftriaxone 50-75 mg/kg/d IV/IM as a single dose or divided q12h Do not use in infants <6 wk of age; parenteral antibiotic with long half-life; may displace bilirubin from albumin Cefotaxime 150 mg/kg/d IV/IM divided q6-8h Safe to use in infants <6 wk of age; used with ampicillin in infants aged 2-8 wk Ampicillin 100 mg/kg/d IV/IM divided q8h Used with gentamicin in neonates <2 wk of age; for enterococci and patients allergic to cephalosporins Gentamicin Term neonates <7 d: 3.5-5 mg/kg/dose IV q24h
Infants and children <5 y: 2.5 mg/kg/dose IV q8h or single daily dosing with normal renal function of 5-7.5 mg/kg/dose IV q24h
Children >5 y: 2-2.5 mg/kg/dose IV q8h or single daily dosing with normal renal function of 5-7.5 mg/kg/dose IV q24hMonitor blood levels and kidney function if therapy extends >48 h
- Infants and children aged 2 months to 2 years with a first febrile urinary tract infection
- If clinical findings indicate that immediate antibiotic therapy is indicated, a urine specimen for urinalysis and culture should be obtained by means of suprapubic aspiration or catheterization before treatment is started.
- Recent evidence suggests no significant differences in efficacy between IV antibiotic therapy given for 3 days followed by oral therapy for another 11 days and 14 days of oral therapy. These data are based on a randomized control trial of 306 children aged 1-24 months to compare oral cefixime for 14 days with IV cefotaxime for 3 days followed by oral cefixime for 11 days. No notable differences were observed in short- or long-term outcomes (eg, clinical response, reinfection, renal scars at 6 mo). These data led to the recommendation that children with a febrile urinary tract infection should receive oral treatment with a second- or third-generation cephalosporin, amoxicillin clavulanate, or sulfamethoxazole-trimethoprim (SMZ-TMP) (see Table 4).
- Table 4. Antibiotic Agents for the Oral Treatment of Urinary Tract Infection
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[ CLOSE WINDOW ]Table
Antibacterial Agent Daily Dosage Sulfisoxazole 120-150 mg/kg divided q4-6h Sulfamethoxazole and trimethoprim 6-12 mg/kg TMP, 30-60 mg/kg SMZ divided q12h Amoxicillin and clavulanic acid 20-40 mg/kg divided q8h Cephalexin 20-50 mg/kg divided q6h Cefixime 8 mg/kg divided q12-24h Cefpodoxime 10 mg/kg divided q12h Loracarbef 15-30 mg/kg divided q12h Nitrofurantoin* 5-7 mg/kg divided q6h *Nitrofurantoin may be used to treat lower urinary tract infections. However, because of its limited tissue penetration, nitrofurantoin is not suitable for the treatment of kidney infection.Antibacterial Agent Daily Dosage Sulfisoxazole 120-150 mg/kg divided q4-6h Sulfamethoxazole and trimethoprim 6-12 mg/kg TMP, 30-60 mg/kg SMZ divided q12h Amoxicillin and clavulanic acid 20-40 mg/kg divided q8h Cephalexin 20-50 mg/kg divided q6h Cefixime 8 mg/kg divided q12-24h Cefpodoxime 10 mg/kg divided q12h Loracarbef 15-30 mg/kg divided q12h Nitrofurantoin* 5-7 mg/kg divided q6h - A child treated with oral antibiotics should not be acutely ill or toxic, and he or she should not have persistent vomiting or moderate-to-severe dehydration.
- Daily follow-up and good compliance is essential with this management.
- Inpatient treatment of children with complicated pyelonephritis
- Provide appropriate parenteral fluids, usually at 1-1.5 times the usual maintenance rate.
- Parenteral treatment with a third-generation cephalosporin, such as ceftriaxone or cefotaxime (Table 3). Add ampicillin if gram-positive cocci are present in the urinary sediment or if no organisms are observed. Gentamicin is an alternative for term infants older than 7 days, for older children, and for adolescents who are allergic to cephalosporins. Monitor renal function and blood aminoglycoside levels if this medication is required for more than 48 hours.
- Results of urine culture and sensitivity studies are usually available within 48 hours. If the pathogen is sensitive to the antibiotic used and if the child is improving, continue treatment with the parenteral route until the child is afebrile for 24-36 hours. An oral antibiotic that is effective against the infecting organism may then be substituted for parenteral therapy (see Table 4).
- The hospitalized patient is usually ready to go home after 48-72 hours. Continue therapeutic doses of antibiotics for a total of 10-14 days of antibiotic therapy. Antibacterial therapy should be given to prevent reinfection (see Table 5 below) and continue at least until a voiding cystourethrography (VCUG) is obtained (if one is to be obtained).
- Table 5. Antibiotic Agents to Prevent Reinfection
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[ CLOSE WINDOW ]Table
Agent Single Daily Dose Nitrofurantoin* 1-2 mg/kg PO Sulfamethoxazole and trimethoprim* 1-2 mg/kg TMP, 5-10 mg/kg SMZ PO Trimethoprim 1-2 mg/kg PO *Do not use nitrofurantoin or sulfa drugs in infants younger than 6 weeks. Reduced doses of an oral first-generation cephalosporin, such as cephalexin at 10 mg/kg, may be used until the child reaches the age of 6 weeks. Ampicillin or amoxicillin are not recommended because of the high incidence of resistant E coli.Agent Single Daily Dose Nitrofurantoin* 1-2 mg/kg PO Sulfamethoxazole and trimethoprim* 1-2 mg/kg TMP, 5-10 mg/kg SMZ PO Trimethoprim 1-2 mg/kg PO
- Children with cystitis
- Children with cystitis usually do not require special medical care other than appropriate antibiotic therapy and symptomatic therapy if the voiding symptoms are marked. Antibiotic therapy is started on the basis of the practitioner's appraisal of the patient's clinical history and urinalysis results before the diagnosis is documented. Systematic reviews of treatments for cystitis in children showed no difference in the efficacy with 7-14 days of therapy compared with 2-4 days. Single-dose or single-day therapy is not recommended in children with cystitis.
- Symptomatic relief for dysuria consists of increasing fluid intake to enhance urine dilution and output, acetaminophen, and nonsteroidal anti-inflammatory drugs. If voiding symptoms are severe and persistent, add phenazopyridine hydrochloride (Pyridium). Do not administer phenazopyridine hydrochloride for longer than 48 hours because of the risk of methemoglobinemia, hemolytic anemia, and other adverse reactions.
- Sitting in a tub of warm water for 20-30 minutes 3-4 times a day often affords symptomatic relief. Patients with severe voiding discomfort may obtain relief by using an appropriately sized rectal suppository of belladonna and opium. Inform the patient to use these suppositories no more than 4 times a day and for no longer than 2 days.
- A 4-day course of an oral antibiotic agent is recommended for the treatment of cystitis (see Table 4). If the clinical response is not satisfactory after 2-3 days, alter therapy on the basis of antibiotic susceptibility.
Medication
Antibiotics are used to treat urinary tract infection (UTI) and to prevent recurrences. Avoid nephrotoxic drugs whenever possible. On occasion, analgesic therapy may be used to provide relief because of voiding symptoms.
Antibiotic agents
These are used for bacterial infections of the urinary tract. Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Ceftriaxone (Rocephin)
Initial parenteral therapy for complicated pyelonephritis in pediatric patients beyond neonatal period.
Adult
1-2 g IV/IM q12-24h
Pediatric
Infants and children: 50-75 mg/kg/d IV/IM divided q12-24h
Decreased elimination half-life with coadministration of high-dose probenecid; possible increased risk of nephrotoxicity with aminoglycosides
Documented hypersensitivity; jaundice; neonates, particularly hyperbilirubinemic premature infants
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Documented hypersensitivity to penicillin, gallbladder, biliary tract, liver, or pancreatic disease, colitis; avoid in neonates (especially if premature) due to potential for bilirubin displacement
Cefotaxime (Claforan)
Used as initial parenteral therapy for pediatric patients with acute complicated pyelonephritis. May be used for neonates or jaundiced patients. In infants, 2- to 8-wk regimen also includes ampicillin. Requires dosing q6-8h.
Adult
1-2 g IV/IM q6-8h
Pediatric
0-4 weeks and <1200 g: 100 mg/kg/d IV/IM divided q12h
>7 days and 1200-2000 g: 150 mg/kg/d IV/IM divided q8h
>7 days and >2000 g: 150 mg/kg/d IV/IM divided q6-8h
Increased concentrations with coadministration of probenecid
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Documented hypersensitivity to penicillin, impaired renal function, history of colitis
Ampicillin (Marcillin, Omnipen, Polycillin)
Parenteral therapy for initial treatment of patients with acute pyelonephritis, with gram-positive cocci in urinary sediment, or when no organisms observed.
Adult
500 mg IV/IM q4-6h
Pediatric
100-200 mg/kg/d IV/IM divided q4-6h
Increased concentrations with coadministration of probenecid
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Documented hypersensitivity to cephalosporin; dosage modification needed with impaired kidney function
Amoxicillin and clavulanate (Augmentin)
PO therapy for completion of initial treatment of infection with susceptible organism. Amoxicillin inhibits bacterial cell-wall synthesis by binding to penicillin-binding proteins. Addition of clavulanate inhibits beta-lactamase producing bacteria.
Good alternative antibiotic for patients allergic or intolerant to macrolide class. Usually well tolerated and provides good coverage to most infectious agents. Not effective against Mycoplasma or and Legionella species. Half-life of PO dosage form 1-1.3 h. Has good tissue penetration but does not enter CSF.
For patients >3 mo, base dosing protocol on amoxicillin content. Because of different amoxicillin–clavulanic acid ratios in 250-mg tab (250-125) vs 250 mg chewable-tab (250-62.5), do not use 250-mg tab until child weighs >40 kg.
Adult
500-875 mg q12h PO or 250-500 mg PO q8h for 7-10 d
Pediatric
<3 months: 125 mg/5 mL PO susp; 30 mg/kg/d (based on amoxicillin component) divided bid for 7-10 d
>3 months: if 200 mg/5 mL or 400 mg/5 mL susp used, 45 mg/kg/d PO divided q12h; 125 mg/5 mL or 250 mg/5 mL susp used, 40 mg/kg/d PO divided bid for 7-10 d
>40 kg: Administer as in adults
Coadministration with warfarin or heparin increases risk of bleeding; may act synergistically against selected microorganisms when coadministered with aminoglycosides; coadministration with allopurinol may increase incidence of amoxicillin rash; may decrease efficacy of PO contraceptives when administered concomitantly
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Diarrhea may occur; adjust dose in renal impairment; cross-allergy may occur with other beta-lactams and cephalosporins
Gentamicin (Garamycin)
Initial parenteral therapy for patients with bacterial pyelonephritis who are allergic to cephalosporins. For complicated UTI, sometimes used in combination with a cephalosporin.
Adult
3-6 mg/kg/d IV/IM divided q8h
Pediatric
Premature neonate and <1000 g: 3.5 mg/kg/dose IV/IM q48h
Term neonate and <7 days: 3.5-5 mg/kg/dose IV q24h
Infants and children <5 years: 2.5 mg/kg/dose IV q8h
Children >5 years: 2-2.5 mg/kg/dose IV q8h
Increased toxicity with concurrent use of amphotericin B, cephalosporins, penicillins, loop diuretics, vancomycin, cisplatin, indomethacin; potentiates neuromuscular blocking agents and botulinum toxin
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in neonates; caution in renal impairment, auditory or vestibular impairment, hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission; dosage modification needed with renal impairment
Sulfisoxazole (Gantrisin)
PO treatment for bacterial UTI. Sulfonamide derivative that exerts bacteriostatic action by antagonizing para-aminobenzoic acid (PABA), an essential component in folic acid synthesis.
Adult
2-4 g PO initially, then 4-8 g/d PO divided q4-6h
Pediatric
<2 months: Contraindicated
>2 months: 75 mg/kg PO loading dose, then 120-150 mg/kg/d PO divided q4-6h; not to exceed 6 g/d
May enhance anticoagulation action effects of warfarin and cause hemorrhage; may enhance anesthetic effects of thiopental; risk of nephrotoxicity may increase with concurrent cyclosporine; may increase serum hydantoin levels when administered concurrently; may enhance methotrexate-induced bone marrow when administered concurrently; may increase sulfonylurea concentrations and cause hypoglycemia in diabetes; may prolong bioavailability of tolbutamide when administered concurrently; coadministration with diuretics may increase incidence of thrombocytopenia with purpura
Concurrent administration with indomethacin may increase free drug concentration of sulfonamide; sulfonamides may form precipitate in acidic urine when used concomitantly with methenamine mandelate; probenecid and salicylates may displace sulfonamides from plasma albumin, increasing free-drug concentrations and potentiating its toxicity
Documented hypersensitivity; porphyria; urinary tract obstruction; infants <2 mo; pregnant women in third trimester; nursing mothers
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Pregnancy category D near term because of potential displacement of bilirubin causing kernicterus; G-6-PD deficiency; hepatic or renal impairment; dosage modification and concern about crystalluria with impaired renal function
Sulfamethoxazole and trimethoprim (Bactrim, Cotrim, Septra)
PO treatment for bacterial UTI and for prevention of reinfection.
Adult
UTI: TMP 160 mg–SMZ 800 mg (ie, 1 double-strength tab) PO q12h for 10-14 d
Pediatric
<2 months: Contraindicated
>2 months:
UTI: 6-12 mg/kg/d (based on trimethoprim component) PO divided q12h
Reinfection prophylaxis: 1-2 mg/kg/d (based on trimethoprim component) PO qd
Decreases clearance of warfarin; displacement of methotrexate from protein binding sites; increases effect of sulfonylureas, phenytoin, and thiopental; decreases serum cyclosporine concentrations
Documented hypersensitivity; porphyria; megaloblastic anemia due to folate deficiency; age <2 mo
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Pregnancy category D near term because of potential displacement of bilirubin causing kernicterus; G-6-PD deficiency; impaired renal or hepatic function; dosage adjustment needed with renal impairment
Cephalexin (Biocef, Cefanex, Keflex)
PO treatment for bacterial UTI and for prevention of infection in infants <6-8 wk.
Adult
250-500 mg PO q6h
Pediatric
<6-8 weeks: 20-50 mg/kg/d PO divided q6h
Prophylaxis: 10 mg/kg/d PO qd
Probenecid increases serum concentrations; coadministration with aminoglycosides increases nephrotoxic potential
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Documented hypersensitivity with penicillin; colitis; dosage modification needed with renal impairment
Cefixime (Suprax)
PO treatment for acute bacterial UTI. By binding to 1 or more penicillin-binding proteins, arrests bacterial cell-wall synthesis and inhibits bacterial growth.
Adult
400 mg/d PO divided q12-24h
Pediatric
8 mg/kg/d PO q12-24h; not to exceed 400 mg/d
Probenecid increases serum concentration; coadministration of aminoglycosides increases nephrotoxicity; may increase serum carbamazepine concentration
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Documented hypersensitivity to penicillin; impaired renal function; colitis; dosage modification needed with impaired renal function
Cefpodoxime (Vantin)
PO treatment for acute bacterial UTI. Indicated to manage infections caused by susceptible mixed aerobic-anaerobic microorganisms.
Adult
100-400 mg/dose PO q12h
Pediatric
>6 months to 12 years: 10 mg/kg/d PO divided q12h
>12 years: Administer as in adults
Reduced absorption with coadministration of antacids and H2-receptor antagonists; reduced renal excretion with probenecid
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Documented hypersensitivity to penicillin; colitis; impaired renal function; with impaired renal function, reduce dosage by one half if CrCl 10-30 mL/min and by three fourths if <10 mL/min (high doses may cause CNS toxicity); bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged or repeated therapy
Loracarbef (Lorabid)
PO treatment for acute bacterial UTI. Beta-lactam antibiotic, which inhibits bacterial cell-wall synthesis by binding to 1 or more penicillin-binding proteins. Inhibits final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, inhibiting cell-wall biosynthesis.
Adult
Acute pyelonephritis: 400 mg PO q12h for 14 d
Lower UTI: 200 mg PO qd for 7 d
Pediatric
6 months to 12 years: 15-30 mg/kg/d PO divided q12h
>12 years: Administer as in adults
Inhibited renal excretion with probenecid; aminoglycosides may have additive nephrotoxic effects
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Documented hypersensitivity to other beta-lactam antibiotics (eg, penicillins, cephalosporins); colitis; dosage modification needed with impaired renal function
Nitrofurantoin (Furadantin, Macrobid, Macrodantin)
PO treatment of bacterial lower UTI (cystitis) and for prevention of reinfection. Synthetic nitrofuran; interferes with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A. Bacteriostatic at low concentrations (5-10 mcg/mL) and bactericidal at higher concentrations.
Adult
Acute UTI: 50-100 mg PO q6h
Prevention of reinfection: 50-100 mg PO qhs
Pediatric
Lower UTI: 5-7 mg/kg/d PO divided q6h
Prevention of reinfection: 1-2 mg/kg/d PO divided q12-24h
Decreases renal secretion with probenecid; decreases rate and extent of absorption with antacids; drugs that delay gastric emptying (eg, anticholinergics) increase absorption
Documented hypersensitivity; renal impairment; age <1 mo
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
G-6-PD deficiency; may cause severe and irreversible peripheral neuropathy that can be fatal; renal impairment, diabetes, electrolyte imbalance, anemia, and vitamin B deficiency increase risk for adverse effects; prolonged use of antibiotics may result in fungal or bacterial overgrowth of resistant or nonsusceptible organisms
Trimethoprim (Proloprim, Trimpex)
PO antibiotic to prevent UTI. Dihydrofolate reductase inhibitor that prevents production of tetrahydrofolic acid in bacteria. Active in vitro against broad range of gram-positive and gram-negative bacteria, including uropathogens, eg, Enterobacteriaceae and Staphylococcus saprophyticus. Resistance usually mediated by decreased cell permeability or alterations amount or structure of dihydrofolate reductase. Demonstrates synergy with sulfonamides, potentiating inhibition of bacterial tetrahydrofolate production.
Adult
Prophylaxis: 100 mg PO qd
Pediatric
Prophylaxis: 1-2 mg/kg PO qd
Increased risk of folate deficiency with coadministration of other folate antagonists (eg, methotrexate, pyrimethamine); increased serum levels of phenytoin, cyclosporine, dapsone, procainamide, rifampin, and warfarin
Documented hypersensitivity; megaloblastic anemia due to folate deficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Impaired renal or hepatic function or possible folate deficiency; decreased dose needed with renal dysfunction
Systemic analgesics
These agents are used to provide relief from voiding symptoms due to urinary tract infection.
Acetaminophen (Tylenol, Panadol, Tempra)
Nonopioid systemic analgesic used for moderate voiding discomfort caused by UTI.
Adult
325-650 mg PO q4-6h
Pediatric
Neonates: 10-15 mg/kg PO q6-8h
Infants and children: 10-15 mg/kg PO q4-6h
Hepatic toxicity increased by enzyme inducers (eg, barbiturates, carbamazepine, phenytoin, alcohol; especially long-term use); coadministration of rifampin may decrease therapeutic effect
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Avoid products containing aspartame with phenylketonuria; many nonprescription products contain acetaminophen, query patient about their use; concentrations of products vary, prescribe precise dose in milligrams
Urinary bladder analgesics
These agents are used to relieve burning, spasticity, and pain during voiding due to urinary tract infection.
Phenazopyridine (Azo-Standard, Pyridium, Urodine)
Exerts local topical anesthetic or analgesic action on urinary mucosa. Used for symptomatic relief of pain, burning, urgency, frequency, and other discomforts arising from irritation of lower urinary tract mucosa caused by infection, trauma, surgery, endoscopic procedures, passage of sound, or catheters. Analgesic action may reduce or eliminate need for systemic analgesics.
Adult
100-200 mg PO q4-6h for 2 d
Pediatric
12 mg/kg/d PO divided q8h for 2 d
May cause false-negative results for Clinistix, Tes-tape, Ictotest, Acetest, Ketostix, or urinalysis tests based on spectrometry or color reactions
Documented hypersensitivity; liver or kidney disease; do not use if CrCl <50 mL/min
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Impaired renal function; administer after meals; will likely discolor urine
More on Urinary Tract Infection |
| Overview: Urinary Tract Infection |
| Differential Diagnoses & Workup: Urinary Tract Infection |
 Treatment & Medication: Urinary Tract Infection |
| Follow-up: Urinary Tract Infection |
| Multimedia: Urinary Tract Infection |
| References |
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Further Reading
Keywords
urinary tract infection, UTI, cystitis, pyelonephritis, urethritis, urinary tract abnormality, bacteriuria, upper urinary tract infection, lower tract urinary infection, pyuria, uropathogens, periurethral colonization, treatment, diagnosis
